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Jiang H, Bai X. Bibliometric and Bioinformatics Analysis of Renal Impairment in Multiple Myeloma: Trends and Research Hotspots, and Associated Genetic Pathways (2000-2023). J Multidiscip Healthc 2025; 18:1147-1162. [PMID: 40026868 PMCID: PMC11872101 DOI: 10.2147/jmdh.s501551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2024] [Accepted: 02/12/2025] [Indexed: 03/05/2025] Open
Abstract
Objective This study aims to perform a bibliometric visual analysis and bioinformatics analysis to explore the research hotspots and trends of renal impairment in multiple myeloma, including the associated genes and signal pathways over the past two decades. Methods The Web of Science Core Collection database was utilized as the data source to retrieve literature on renal impairment in multiple myeloma from 2000 to 2023. The selected literature was analyzed using bibliometric and bioinformatics software, including Bibliometrix, VOSviewer 1.6.16, Citespace 5.7R5 and Cytoscape 3.7.1 software. Results This study encompassed 2152 articles that were published from 2000 to 2023, demonstrating an overall upward trend in annual publications and citations. Among the set of 27 core journals examined, the "CUREUS JOURNAL OF MEDICAL SCIENCE" exhibited the highest frequency of publications, while "BLOOD" emerged as the most frequently cited source. The global research on renal impairment in multiple myeloma research included contributions from 84 countries/regions, with the United States leading in terms of publication output and Mayo Clinic playing a central role in fostering inter-agency collaboration. Keywords such as "daratumumab", "carfilzomib", "diagnostic criteria" and "kidney biopsy" included recent research hotspots. We hypothesized that the TP53, AKT1, MYC, and CTNNB1 genes were involved in epithelial cell proliferation and the positive regulation of the MAPK cascade through signaling receptor activator activity, receptor-ligand interactions, and cytokine receptor binding. Simultaneously, they were implicated in renal impairment in multiple myeloma via the PI3K/Akt and MAPK signaling pathways. Conclusion This research employed bibliometric visual analysis and bioinformatics analysis to identify the current focus and future directions of studying renal impairment in multiple myeloma, as well as to explore the associated genes and signaling pathways. The management of renal impairment in patients with multiple myeloma has a significant impact on medical costs. Clinical physicians need to consider how to allocate medical resources reasonably, ensure that patients can receive necessary diagnosis and treatment, and explore cost-effective treatment options. The management of these patients requires interdisciplinary medical services, which should integrate basic and clinical research, especially the development of new treatment plans, to improve patients' quality of life and guide future treatment choices.
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Affiliation(s)
- Huinan Jiang
- Department of Hematology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China
| | - Xue Bai
- Department of Health Management, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China
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Li S, Meng X, Peng B, Huang J, Liu J, Xiao H, Ma L, Liu Y, Tang J. Cell membrane-based biomimetic technology for cancer phototherapy: Mechanisms, recent advances and perspectives. Acta Biomater 2024; 174:26-48. [PMID: 38008198 DOI: 10.1016/j.actbio.2023.11.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 11/04/2023] [Accepted: 11/20/2023] [Indexed: 11/28/2023]
Abstract
Despite significant advances in medical technology and antitumour treatments, the diagnosis and treatment of tumours have undergone remarkable transformations. Noninvasive phototherapy methods, such as photodynamic therapy (PDT) and photothermal therapy (PTT), have gained significant interest in antitumour medicine. However, traditional photosensitisers or photothermal agents face challenges like immune system recognition, rapid clearance from the bloodstream, limited tumour accumulation, and phototoxicity concerns. Researchers combine photosensitisers or photothermal agents with natural cell membranes to overcome these obstacles to create a nano biomimetic therapeutic platform. When used to coat nanoparticles, red blood cells, platelets, cancer cells, macrophages, lymphocytes, and bacterial outer membranes could provide prolonged circulation, tumour targeting, immune stimulation, or antigenicity. This article covers the principles of cellular membrane biomimetic nanotechnology and phototherapy, along with recent advancements in applying nano biomimetic technology to PDT, PTT, PCT, and combined diagnosis and treatment. Furthermore, the challenges and issues of using nano biomimetic nanoparticles in phototherapy are discussed. STATEMENT OF SIGNIFICANCE: Currently, there has been significant progress in the field of cell membrane biomimetic technology. Researchers are exploring its potential application in tumor diagnosis and treatment through phototherapy. Scholars have conducted extensive research on combining cell membrane technology and phototherapy in anticancer diagnosis and treatment. This review aims to highlight the mechanisms of phototherapy and the latest advancements in single phototherapy (PTT, PDT) and combination phototherapy (PCT, PRT, and PIT), as well as diagnostic approaches. The review provides an overview of various cell membrane technologies, including RBC membranes, platelet membranes, macrophage cell membranes, tumour cell membranes, bacterial membranes, hybrid membranes, and their potential for anticancer applications under phototherapy. Lastly, the review discusses the challenges and future directions in this field.
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Affiliation(s)
- Songtao Li
- Traditional Chinese Medicine (TCM) Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China; Clinical School of Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China
| | - Xiangrui Meng
- Traditional Chinese Medicine (TCM) Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China; Clinical School of Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China.
| | - Bo Peng
- Clinical School of Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China
| | - Ju Huang
- Traditional Chinese Medicine (TCM) Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China; Clinical School of Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China
| | - Jingwen Liu
- Traditional Chinese Medicine (TCM) Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China
| | - Hang Xiao
- College of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, PR China
| | - Li Ma
- College of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, PR China
| | - Yiyao Liu
- School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, PR China.
| | - Jianyuan Tang
- Traditional Chinese Medicine (TCM) Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China; Clinical School of Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China.
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Li S, Zhang M, Liu J, Liu S, Zhu C, Shang D, Guan Y, Wang Q. Risk nomogram for assessing renal recovery in patients with newly diagnosed multiple myeloma-related renal impairment. Curr Probl Cancer 2023; 47:100962. [PMID: 37247442 DOI: 10.1016/j.currproblcancer.2023.100962] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 03/13/2023] [Accepted: 05/01/2023] [Indexed: 05/31/2023]
Abstract
To determine risk factors affecting renal recovery in newly diagnosed multiple myeloma (NDMM) patients with renal impairment (RI) and establish a risk nomogram. This multi-center, retrospective cohort study included 187 NDMM patients with RI, 127 of whom were admitted to Huashan Hospital and assigned to the training cohort and 60 were admitted to Changzheng Hospital and assigned to the external validation cohort. The baseline data of the 2 cohorts were compared, and survival and renal recovery rates were analyzed. Independent risk factors affecting renal recovery were determined by binary logistic regression analysis, and a risk nomogram was established and subsequently tested in the external validation cohort. Results: The median overall survival (OS) improved in patients who achieved renal recovery etc within 6 courses of MM directed treatment compared with patients without renal recovery. Median time to renal recovery was 2.65 courses, and the cumulative renal recovery rate during the first 3 courses was 75.05%. Involved serum free light chain (sFLC) ratio of >120 at diagnosis, time from renal impairment to treatment > 60 days, and a hematologic response without a very good partial remission (VGPR) or better resulted as independent risk factors for renal recovery during the first 3 courses. The established risk nomogram had good discriminative ability and accuracy. Involved sFLC was a key factor affecting renal recovery. Starting treatment as soon as possible after detecting RI and achieving deep hematologic remission during the first 3 courses of treatment helped achieve renal recovery and improve prognosis.
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Affiliation(s)
- Shaobo Li
- Department of Hematology, Huashan Hospital, Fudan University, Shanghai, 200040, China; Department of Nuclear Medicine, Peking University Cancer Hospital Inner Mongolia Campus/the Affiliated Cancer Hospital of Inner Mongolia Medical University, Hohhot 010020, China
| | - Min Zhang
- Department of Nephrology, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Jin Liu
- Department of Hematology, Myeloma & Lymphoma Center, Changzheng Hospital, Naval Medical University, Shanghai, 200003, China
| | - Shaojun Liu
- Department of Nephrology, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Chen Zhu
- Department of Hematology, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Da Shang
- Department of Nephrology, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Yi Guan
- Department of Nephrology, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Qian Wang
- Department of Hematology, Huashan Hospital, Fudan University, Shanghai, 200040, China.
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Terrades NR, Senin A, Azancot MA, Gironella M, Toapanta N, Bermejo S, Martin L, Caravaca-Fontán F, Cuellar C, Martínez-Lopez J, Rodríguez E, Bestard O, Soler MJ. Role of light chain clearance in the recovery of renal function in multiple myeloma: another point of view. Clin Kidney J 2023; 16:1014-1021. [PMID: 37260999 PMCID: PMC10229297 DOI: 10.1093/ckj/sfad022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Indexed: 09/26/2023] Open
Abstract
BACKGROUND Acute kidney injury (AKI) in patients with multiple myeloma (MM) requiring renal replacement treatment (RRT) is associated with high morbidity and mortality. Early reduction of serum free light chains (FLC) using both targeted therapy against MM and intensive hemodialysis (IHD) may improve renal outcomes. We evaluated the effectiveness of two different RRT techniques on renal recovery in an MM patient population: standard dialysis procedure vs IHD with either polymethylmethacrylate (PMMA) or hemodiafiltration with endogenous reinfusion (HFR). METHODS This was a multicentric retrospective study with severe AKI related to MM, between 2011 and 2018. Twenty-five consecutive patients with AKI secondary to MM requiring RRT were included. Patients that underwent IHD received six dialysis sessions per week during the first 14 days (PMMA vs HFR). All patients were diagnosed with de novo MM or first relapsed MM. Primary outcome was renal recovery defined as dialysis-free at 6 months follow-up. RESULTS A total of 25 patients were included. Seventeen patients received IHD and eight standard dialysis. All patients were treated with targeted therapy, 84% bortezomib-based. Of the 25 patients included, 14 (56%) became dialysis independent. We observed a higher proportion of patients who received IHD in the group who recovered kidney function compared with those who remained in HD (92.9% vs 36.4%, P = .007). In our study, the use of IHD to remove FLC had a statistically significant association with renal recovery compared with the standard dialysis group (P = .024). CONCLUSION Early reduction of FLC with IHD as an adjuvant treatment along with MM-targeted therapy may exert a positive impact on renal recovery.
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Affiliation(s)
| | - Alicia Senin
- Hospital Duran i Reynalds, ICO, Hospitalet, Spain
| | - Maria A Azancot
- Department of Nephrology, Hospital Vall d'Hebron, Barcelona, Spain
| | | | - Nestor Toapanta
- Department of Nephrology, Hospital Vall d'Hebron, Barcelona, Spain
| | - Sheila Bermejo
- Department of Nephrology, Hospital Vall d'Hebron, Barcelona, Spain
| | - Lucia Martin
- Department of Hematology, Hospital Vall d'Hebron, Barcelona, Spain
| | | | - Clara Cuellar
- Department of Hematology, Hospital 12 de Octubre, Madrid, Spain
| | | | - Eva Rodríguez
- Department of Nephrology, Hospital del Mar, Barcelona, Spain
| | - Oriol Bestard
- Department of Nephrology, Hospital Vall d'Hebron, Barcelona, Spain
| | - Maria Jose Soler
- Department of Nephrology, Hospital Vall d'Hebron, Barcelona, Spain
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Miki K, Shimamura Y, Maeda T, Moniwa N, Ogawa Y, Shimizu T, Hayashi T, Sakai H, Takizawa H. Successful renal recovery from multiple myeloma-associated crystalline light chain cast nephropathy and accompanying acute kidney injury with early use of bortezomib-based therapy: a case report and literature review. CEN Case Rep 2023; 12:56-62. [PMID: 35854043 PMCID: PMC9892411 DOI: 10.1007/s13730-022-00721-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 07/05/2022] [Indexed: 02/05/2023] Open
Abstract
Crystalline light chain cast nephropathy is a rare distinct morphologic variant of light chain cast nephropathy which is the most common renal lesion associated with multiple myeloma. It is often related to high myeloma tumor burden, severe acute kidney injury, and an unfavorable prognosis. A 79-year-old Japanese man was referred to our medical center with anemia, proteinuria, and acute exacerbation of the serum creatinine accompanying anuria. A renal biopsy showed crystalline cast filling the tubular lumens, injured tubular cells, and inflammatory cells infiltration of interstitium. Serum and urine immunofixation detected a monoclonal protein (IgA-λ and Bence-Jones Protein-λ, respectively), and bone marrow examination observed 64% of plasma cells. IgA-λ type multiple myeloma-associated crystalline light chain cast nephropathy and accompanying acute kidney injury were confirmed. Hydration and emergency hemodialysis were immediately introduced, and the treatment with bortezomib and dexamethasone was initiated. The patient showed successful recovery in renal manifestations. We suggest that early use with bortezomib-based therapy should be considered for patients with acute kidney injury caused by multiple myeloma-associated crystalline light chain cast nephropathy.
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Affiliation(s)
- Kosuke Miki
- Department of Hematology, Teine Keijinkai Medical Center, Sapporo, Hokkaido, Japan.
| | | | - Takuto Maeda
- Department of Nephrology, Teine Keijinkai Medical Center, Sapporo, Hokkaido, Japan
| | - Norihito Moniwa
- Department of Nephrology, Teine Keijinkai Medical Center, Sapporo, Hokkaido, Japan
| | - Yayoi Ogawa
- Hokkaido Renal Pathology Center, Sapporo, Japan
| | - Taku Shimizu
- Department of Hematology, Teine Keijinkai Medical Center, Sapporo, Hokkaido, Japan
| | - Toshiaki Hayashi
- Department of Hematology, Teine Keijinkai Medical Center, Sapporo, Hokkaido, Japan
| | - Hajime Sakai
- Department of Hematology, Teine Keijinkai Medical Center, Sapporo, Hokkaido, Japan
| | - Hideki Takizawa
- Department of Nephrology, Teine Keijinkai Medical Center, Sapporo, Hokkaido, Japan
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Safety and efficacy of autologous stem cell transplantation in dialysis-dependent myeloma patients-The DIADEM study from the chronic malignancies working party of the EBMT. Bone Marrow Transplant 2023; 58:424-429. [PMID: 36681775 DOI: 10.1038/s41409-023-01915-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 12/27/2022] [Accepted: 01/10/2023] [Indexed: 01/22/2023]
Abstract
The role of high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) in the treatment of myeloma (MM) patients with severe and/or dialysis-dependent renal impairment remains uncertain. We report on the outcomes of 110 patients (median age 57 years) who had become dialysis-dependent pre-ASCT and who underwent a first ASCT between 1997 and 2017. Sixty-three (57%) patients had light chain MM. All patients required dialysis (94% hemodialysis and 6% peritoneal). Forty-four of 71 (62%) patients received bortezomib-based induction regimens and 42 (39%) patients had achieved at least a very good partial response (VGPR) pre-ASCT. Melphalan dosing was as follows: ≤140 mg/m2 (82%), and >140 mg/m2 (18%). The median PFS after ASCT was 35 months (95% CI: 21.5-42.2) and the median OS 102 months (95% CI: 70.4-129.1). At 1, 2, and 5 years after ASCT, 8% (95% CI 3-14%), 13% (6-20%), and 20% (12-29%) of patients, respectively, had achieved dialysis independence. In multivariate analyses of OS and PFS including age at ASCT, response at ASCT, and year of ASCT, younger age at ASCT and better response at ASCT (CR/VGPR/PR vs. MR/SD/progression) were significantly associated with better OS and PFS.
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Travassos PNC, de Barros Silva PG, Freitas MO, Braga MDM, Duarte FB, de Oliveira Maia JK, Pitombeira H, de Sousa JH, Alves APNN. Risk factors for renal impairment in patients with hematological cancer receiving antineoplastic treatment. Support Care Cancer 2022; 30:7271-7280. [PMID: 35596773 DOI: 10.1007/s00520-022-07159-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Accepted: 05/16/2022] [Indexed: 12/01/2022]
Abstract
PURPOSE Antineoplastic treatments, mainly chemotherapy, affect the kidneys, causing toxicity, and can trigger acute and chronic kidney injuries. This study aimed to analyze the prevalence of renal disorders in patients with oncohematological neoplasms receiving antineoplastic treatment. METHODS This retrospective cohort study included 75 patients with hematological cancer who underwent chemotherapy between 2012 and 2018 in the Hematology Sector of the Walter Cantídeo University Hospital of the Federal University of Ceará. Sociodemographic and clinical data, blood biochemical assessment findings, and glomerular filtration rate (GFR) were analyzed using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. The data were tabulated; transferred to the Statistical Package for the Social Sciences software, version 20.0; and analyzed using Pearson's chi-square test or Fisher's exact test for categorical variables followed by a multinomial logistic regression model (p < 0.05). RESULTS The prevalence of renal disorders was 52.4% according to the CKD-EPI equation for GFR events. There was a significant association between the decrease in GFRs and the following variables: female sex (p = 0.002), diagnosis of multiple myeloma (p = 0.008), start of treatment within 40 days (p = 0.005), and the following antineoplastic treatments: cyclophosphamide, vincristine, and prednisone (p = 0.026); irarubicin (p = 0.032); azacytidine, dexamethasone, and cyclophosphamide (p < 0.001); zoledronic acid (p < 0.001); and pamidronate (p = 0.012). CALGB 8811 (p < 0.001) was inversely associated with a reduction in the GFR. CONCLUSIONS The prevalence of renal disorders was high in patients with oncohematological neoplasms receiving antineoplastic treatment. This requires periodic monitoring of the evaluation of renal function since reductions in GFRs were significantly associated with different treatment protocols used.
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Affiliation(s)
| | | | | | | | | | | | - Helena Pitombeira
- Hematology Section, Walter Cantídio University Hospital, Fortaleza, Ceará, Brazil
| | | | - Ana Paula Negreiros Nunes Alves
- Pathology and Legal Medicine, Medical School, Federal University of Ceará, Fortaleza, Ceará, Brazil
- Clinical Dentistry Department, Dentistry School, Federal University of Ceará, Fortaleza, Ceará, Brazil
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Serum Free Light-Chain Ratio at Diagnosis Is Associated with Early Renal Damage in Multiple Myeloma: A Case Series Real-World Study. Biomedicines 2022; 10:biomedicines10071657. [PMID: 35884962 PMCID: PMC9313319 DOI: 10.3390/biomedicines10071657] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 06/29/2022] [Accepted: 07/08/2022] [Indexed: 11/17/2022] Open
Abstract
The serum free light-chain (FLC) ratio is a sensitive tool for the differential diagnosis of plasma cell disorders and is biomarker of multiple myeloma (MM) progression from premalignant conditions. Here, we investigate the potential role of FLC ratio at diagnosis in identifying early renal damage in MM patients and other correlations with clinical, laboratory, and molecular findings. A total of 34 MM patients who had undergone autologous stem cell transplantation were included in this retrospective case series study, and FLC quantification was performed with nephelometric assays. In our study, sFLC ratio was significantly associated with light-chain MM and β-2 microglobulin levels, likely indicating a high disease burden at diagnosis, especially in patients without heavy chain M-protein at serum electrophoresis. Moreover, the sFLC ratio was inversely correlated with glomerular filtration rate, possibly identifying early renal damage in MM patients. Our preliminary results confirm the importance of early sFLC evaluation, especially in patients with the light-chain MM type and low disease burden, to minimize the risk of late renal failure.
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Donati G, Zappulo F, Maietti E, Scrivo A, Gasperoni L, Zamagni E, Tacchetti P, Pantani L, Baraldi O, Comai G, Cappuccilli M, Cavo M, La Manna G. Early Light Chains Removal and Albumin Levels with a Double Filter-Based Extracorporeal Treatment for Acute Myeloma Kidney. Toxins (Basel) 2022; 14:toxins14060391. [PMID: 35737052 PMCID: PMC9229388 DOI: 10.3390/toxins14060391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 05/27/2022] [Accepted: 06/02/2022] [Indexed: 11/16/2022] Open
Abstract
Renal impairment in Multiple Myeloma (MM) represents one of the most important factors that influences patient survival. In fact, before the introduction of modern chemotherapy, less than 25% of patients with acute kidney injury (AKI) and MM who required dialysis recovered sufficient renal function to become independent from dialysis, with a median overall survival of less than 1 year. There are many other factors involved in determining patient survival. In this study we aimed to investigate the role of double filter-based extracorporeal treatment for removal of serum free light chains (sFLC) in acute myeloma kidney (AKI for MM) and to evaluate patient overall survival. All patients received Bortezomib-based chemotherapy and extracorporeal treatment for sFLC removal. For each session 2 dialyzers of the same kind were used. The dialytic dose was not related to the degree of renal function but to the removal of sFLC. The factors that have been found to be significantly associated with lower mortality were reduction of sFLC at day 12 and day 30, >50% reduction of sFLC at day 30, number of sessions and independence from dialysis. Among baseline characteristics, albumin level was statistically associated with the patients’ outcome. Our analysis highlights the importance of the early treatment for removal of sFLC in AKI for MM. These results indicate that the early removal of sFLC can improve patient’s outcome.
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Affiliation(s)
- Gabriele Donati
- Nephrology, Dialysis and Renal Transplantation Unit, Azienda Ospedaliero-Universitaria di Modena, Surgical, Medical, Dental and Morphological Sciences Department (CHIMOMO), University of Modena and Reggio Emilia, 41124 Modena, Italy;
| | - Fulvia Zappulo
- Nephrology Dialysis and Renal Transplantation Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Department of Experimental Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy; (F.Z.); (A.S.); (L.G.); (O.B.); (G.C.); (M.C.)
| | - Elisa Maietti
- Department of Biomedical and Neuromotor Sciences-DIBINEM, University of Bologna, 40138 Bologna, Italy;
| | - Anna Scrivo
- Nephrology Dialysis and Renal Transplantation Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Department of Experimental Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy; (F.Z.); (A.S.); (L.G.); (O.B.); (G.C.); (M.C.)
| | - Lorenzo Gasperoni
- Nephrology Dialysis and Renal Transplantation Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Department of Experimental Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy; (F.Z.); (A.S.); (L.G.); (O.B.); (G.C.); (M.C.)
| | - Elena Zamagni
- Hematology and Oncology Unit “Lorenzo & Ariosto Seràgnoli”, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy; (E.Z.); (P.T.); (L.P.); (M.C.)
| | - Paola Tacchetti
- Hematology and Oncology Unit “Lorenzo & Ariosto Seràgnoli”, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy; (E.Z.); (P.T.); (L.P.); (M.C.)
| | - Lucia Pantani
- Hematology and Oncology Unit “Lorenzo & Ariosto Seràgnoli”, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy; (E.Z.); (P.T.); (L.P.); (M.C.)
| | - Olga Baraldi
- Nephrology Dialysis and Renal Transplantation Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Department of Experimental Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy; (F.Z.); (A.S.); (L.G.); (O.B.); (G.C.); (M.C.)
| | - Giorgia Comai
- Nephrology Dialysis and Renal Transplantation Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Department of Experimental Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy; (F.Z.); (A.S.); (L.G.); (O.B.); (G.C.); (M.C.)
| | - Maria Cappuccilli
- Nephrology Dialysis and Renal Transplantation Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Department of Experimental Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy; (F.Z.); (A.S.); (L.G.); (O.B.); (G.C.); (M.C.)
| | - Michele Cavo
- Hematology and Oncology Unit “Lorenzo & Ariosto Seràgnoli”, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy; (E.Z.); (P.T.); (L.P.); (M.C.)
| | - Gaetano La Manna
- Nephrology Dialysis and Renal Transplantation Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Department of Experimental Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy; (F.Z.); (A.S.); (L.G.); (O.B.); (G.C.); (M.C.)
- Correspondence:
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Kundu S, Jha SB, Rivera AP, Flores Monar GV, Islam H, Puttagunta SM, Islam R, Sange I. Multiple Myeloma and Renal Failure: Mechanisms, Diagnosis, and Management. Cureus 2022; 14:e22585. [PMID: 35371791 PMCID: PMC8958144 DOI: 10.7759/cureus.22585] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/24/2022] [Indexed: 11/05/2022] Open
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11
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Braet P, Sartò GVR, Pirovano M, Sprangers B, Cosmai L. Treatment of Acute Kidney Injury in Cancer Patients. Clin Kidney J 2021; 15:873-884. [PMID: 35498895 PMCID: PMC9050558 DOI: 10.1093/ckj/sfab292] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Indexed: 11/22/2022] Open
Abstract
Acute kidney injury (AKI), either of pre-renal, renal or post-renal origin, is an important complication in cancer patients, resulting in worse prognosis, withdrawal from effective oncological treatments, longer hospitalizations and increased costs. The aim of this article is to provide a literature review of general and cause-specific treatment strategies for AKI, providing a helpful guide for clinical practice. We propose to classify AKI as patient-related, cancer-related and treatment-related in order to optimize therapeutic interventions. In the setting of patient-related causes, proper assessment of hydration status and avoidance of concomitant nephrotoxic medications is key. Cancer-related causes mainly encompass urinary compression/obstruction, direct tumoural kidney involvement and cancer-induced hypercalcaemia. Rapid recognition and specific treatment can potentially restore renal function. Finally, a pre-treatment comprehensive evaluation of risks and benefits of each treatment should always be performed to identify patients at high risk of treatment-related renal damage and allow the implementation of preventive measures without losing the potentialities of the oncological treatment. Considering the complexity of this field, a multidisciplinary approach is necessary with the goal of reducing the incidence of AKI in cancer patients and improving patient outcomes. The overriding research goal in this area is to gather higher quality data from international collaborative studies.
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Affiliation(s)
- Pauline Braet
- Division of Nephrology, Department of Internal Medicine, University Hospitals Leuven, Leuven, Belgium
| | - Giulia Vanessa Re Sartò
- Onconephrology Outpatients Clinic, Nephrology and Dialysis, ASST Santi Carlo e Paolo, Fatebenefratelli Sacco, Fatebenefratelli Hospital, Milan, Italy
| | - Marta Pirovano
- Onconephrology Outpatients Clinic, Nephrology and Dialysis, ASST Santi Carlo e Paolo, Fatebenefratelli Sacco, Fatebenefratelli Hospital, Milan, Italy
| | - Ben Sprangers
- Division of Nephrology, Department of Internal Medicine, University Hospitals Leuven, Leuven, Belgium
- Department of Microbiology, Immunology and Transplantation, Laboratory of Molecular Immunology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium
| | - Laura Cosmai
- Onconephrology Outpatients Clinic, Nephrology and Dialysis, ASST Santi Carlo e Paolo, Fatebenefratelli Sacco, Fatebenefratelli Hospital, Milan, Italy
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12
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Theodorakakou F, Dimopoulos MA, Kastritis E. Daratumumab plus CyBorD for patients with newly diagnosed light chain (AL) amyloidosis. Ther Adv Hematol 2021; 12:20406207211058334. [PMID: 34840708 PMCID: PMC8613887 DOI: 10.1177/20406207211058334] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 10/11/2021] [Indexed: 12/19/2022] Open
Abstract
Primary systemic immunoglobulin light chain (AL) amyloidosis is caused by a plasma cell clone of, usually low, malignant potential that expresses CD38 molecules on their surface. Treatment of AL amyloidosis is based on the elimination of the plasma cell clone. The combination of cyclophosphamide–bortezomib–dexamethasone (CyBorD) is the most widely used and is considered a standard of care; however, complete hematologic response rates and organ response rates remain unsatisfactory. Daratumumab, an anti-CD38 monoclonal antibody, has demonstrated encouraging results, with rapid and deep responses, in patients with relapsed or refractory AL amyloidosis as monotherapy with a favorable toxicity profile. The large phase-III, randomized, ANDROMEDA study evaluated the addition of daratumumab to CyBorD in previously untreated patients with AL amyloidosis and demonstrated that addition of daratumumab can substantially improve hematologic complete response rates, survival free from major organ deterioration or hematologic progression, and organ responses. In this review, we discuss the role of daratumumab in the treatment of AL amyloidosis, its mechanism of action, and the results of ANDROMEDA study that led to the first approved therapy for AL amyloidosis.
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Affiliation(s)
- Foteini Theodorakakou
- Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Meletios A Dimopoulos
- Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Efstathios Kastritis
- Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
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13
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Alonso-Titos J, Martínez-Esteban MD, López V, León M, Martin-Reyes G, Ruiz-Esteban P, Hernández D. Monoclonal gammopathy of renal significance: Early diagnosis is key. Nefrologia 2021; 41:502-513. [PMID: 36165133 DOI: 10.1016/j.nefroe.2021.11.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Accepted: 11/19/2020] [Indexed: 06/16/2023] Open
Abstract
Monoclonal gammopathy of renal significance is a clinical-pathological entity grouping renal disorders secondary to the secretion of a monoclonal immunoglobulin synthesized by a B-cell-derived clone and/or plasma cells in a patient with no diagnostic criteria for multiple myeloma. This term applies to a concept recently introduced owing to the need to differentiate this entity from monoclonal gammopathy of undetermined significance, given the negative prognostic impact of its high morbidity and mortality resulting from both renal and systemic involvement, occasionally even progressing to advanced chronic kidney disease. The renal damage occurs via both direct pathogenic mechanisms, with the deposition of the monoclonal protein in different renal structures, as well as indirect mechanisms, acting as an autoantibody provoking dysregulation of the alternative complement pathway. The detection of this monoclonal protein and an early hematologic study are essential, as is the need for a kidney biopsy to establish the associated nephropathological diagnosis. Consequently, this then leads to the start of specific hematologic treatment to detain the production of the monoclonal protein and minimize renal and systemic injury.
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Affiliation(s)
- Juana Alonso-Titos
- Nephrology Department, Carlos Haya Regional University Hospital and University of Malaga, IBIMA, REDinREN (RD16/0009/0006), Malaga, Spain
| | - María Dolores Martínez-Esteban
- Nephrology Department, Carlos Haya Regional University Hospital and University of Malaga, IBIMA, REDinREN (RD16/0009/0006), Malaga, Spain
| | - Verónica López
- Nephrology Department, Carlos Haya Regional University Hospital and University of Malaga, IBIMA, REDinREN (RD16/0009/0006), Malaga, Spain
| | - Myriam León
- Pathology Department, Carlos Haya Regional University Hospital, Malaga, Spain
| | - Guillermo Martin-Reyes
- Nephrology Department, Carlos Haya Regional University Hospital and University of Malaga, IBIMA, REDinREN (RD16/0009/0006), Malaga, Spain
| | - Pedro Ruiz-Esteban
- Nephrology Department, Carlos Haya Regional University Hospital and University of Malaga, IBIMA, REDinREN (RD16/0009/0006), Malaga, Spain
| | - Domingo Hernández
- Nephrology Department, Carlos Haya Regional University Hospital and University of Malaga, IBIMA, REDinREN (RD16/0009/0006), Malaga, Spain.
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14
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Special Considerations for Supportive Care and Management of Complications in Elderly Patients With Multiple Myeloma. CLINICAL LYMPHOMA MYELOMA & LEUKEMIA 2021; 21:812-822. [PMID: 34384735 DOI: 10.1016/j.clml.2021.07.013] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 06/28/2021] [Accepted: 07/12/2021] [Indexed: 12/21/2022]
Abstract
Multiple myeloma is a progressive and incurable hematologic malignancy. It is predominantly a disease of older individuals, with a third of these patients considered to be elderly. In recent years, there has been a focus and emphasis on identifying and stratifying patients based on their functional status and frailty. There are several hallmark complications of the disease-hypercalcemia, renal insufficiency, anemia, bone pain-along with thromboembolism and compromised immunity that are common in patients with multiple myeloma. Due to the wide range of patient ages and functional status, there are, accordingly, different considerations for management of the above complications based on numerous factors, including frailty status. This review focuses on considerations and management of common complications of multiple myeloma in elderly patients. These include renal failure, skeletal complications, anemia, thromboembolism, and infectious complications.
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15
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Renal response in real-world carfilzomib- vs bortezomib-treated patients with relapsed or refractory multiple myeloma. Blood Adv 2021; 5:367-376. [PMID: 33496733 DOI: 10.1182/bloodadvances.2019001059] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Accepted: 08/02/2020] [Indexed: 12/15/2022] Open
Abstract
In the phase 3 ENDEAVOR study, carfilzomib-dexamethasone (Kd) improved survival over bortezomib-dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma (RRMM), regardless of baseline renal function. This real-world study compared renal response in patients with RRMM (1-3 prior lines) and renal impairment (estimated glomerular filtration rate ≤50 mL/min) treated with Kd vs Vd. Electronic medical records data from the Oncology Services Comprehensive Electronic Records database were assessed (from January 2012 through February 2018). Time to renal response (defined according to International Myeloma Working Group criteria) was evaluated using the Kaplan-Meier method and log-rank test. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated for renal overall response (ROR) and renal complete response (RCR) using Cox proportional hazard models adjusted for baseline covariates. Included were 543 Kd-treated and 1005 Vd-treated patients. In line 2 (2L), compared with Vd, Kd achieved significantly higher ROR (51.4% vs 39.6%; P < .0001) and RCR (26.6% vs 22.2%; P = .0229). After baseline covariate adjustment, 2L patients receiving Kd vs Vd were 45% more likely to achieve ROR (IRR, 1.45; 95% CI, 1.18-1.78), and 68% were more likely to achieve RCR (IRR, 1.68; 95% CI, 1.24-2.28). The renal response benefit with Kd remained consistent in 2L to line 4 (4L). In a combined analysis of patients receiving Kd and Vd (2L and 2L-4L), renal responders had longer overall survival and time to next treatment than renal nonresponders. These results demonstrate improved real-world effectiveness of Kd over Vd in RRMM renal rescue, and the positive association between renal response and improved survival.
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16
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Alonso-Titos J, Martínez-Esteban MD, López V, León M, Martin-Reyes G, Ruiz-Esteban P, Hernández D. Monoclonal gammopathy of renal significance: Early diagnosis is key. Nefrologia 2021. [PMID: 33824049 DOI: 10.1016/j.nefro.2020.11.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Monoclonal gammopathy of renal significance is a clinical-pathological entity grouping renal disorders secondary to the secretion of a monoclonal immunoglobulin synthesized by a B-cell-derived clone and/or plasma cells in a patient with no diagnostic criteria for multiple myeloma. This term applies to a concept recently introduced owing to the need to differentiate this entity from monoclonal gammopathy of undetermined significance, given the negative prognostic impact of its high morbidity and mortality resulting from both renal and systemic involvement, occasionally even progressing to advanced chronic kidney disease. The renal damage occurs via both direct pathogenic mechanisms, with the deposition of the monoclonal protein in different renal structures, as well as indirect mechanisms, acting as an autoantibody provoking dysregulation of the alternative complement pathway. The detection of this monoclonal protein and an early hematologic study are essential, as is the need for a kidney biopsy to establish the associated nephropathological diagnosis. Consequently, this then leads to the start of specific hematologic treatment to detain the production of the monoclonal protein and minimize renal and systemic injury.
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Affiliation(s)
- Juana Alonso-Titos
- Nephrology Department, Carlos Haya Regional University Hospital and University of Malaga, IBIMA, REDinREN (RD16/0009/0006), Malaga, Spain
| | - María Dolores Martínez-Esteban
- Nephrology Department, Carlos Haya Regional University Hospital and University of Malaga, IBIMA, REDinREN (RD16/0009/0006), Malaga, Spain
| | - Verónica López
- Nephrology Department, Carlos Haya Regional University Hospital and University of Malaga, IBIMA, REDinREN (RD16/0009/0006), Malaga, Spain
| | - Myriam León
- Pathology Department, Carlos Haya Regional University Hospital, Malaga, Spain
| | - Guillermo Martin-Reyes
- Nephrology Department, Carlos Haya Regional University Hospital and University of Malaga, IBIMA, REDinREN (RD16/0009/0006), Malaga, Spain
| | - Pedro Ruiz-Esteban
- Nephrology Department, Carlos Haya Regional University Hospital and University of Malaga, IBIMA, REDinREN (RD16/0009/0006), Malaga, Spain
| | - Domingo Hernández
- Nephrology Department, Carlos Haya Regional University Hospital and University of Malaga, IBIMA, REDinREN (RD16/0009/0006), Malaga, Spain.
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17
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Theodorakakou F, Dimopoulos MA, Kastritis E. Mutation-dependent treatment approaches for patients with complex multiple myeloma. EXPERT REVIEW OF PRECISION MEDICINE AND DRUG DEVELOPMENT 2021. [DOI: 10.1080/23808993.2021.1893605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Affiliation(s)
- Foteini Theodorakakou
- Plasma Cell Dyscrasia Unit, Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece
| | - Meletios A. Dimopoulos
- Plasma Cell Dyscrasia Unit, Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece
| | - Efstathios Kastritis
- Plasma Cell Dyscrasia Unit, Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece
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18
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Bridoux F, Leung N, Belmouaz M, Royal V, Ronco P, Nasr SH, Fermand JP. Management of acute kidney injury in symptomatic multiple myeloma. Kidney Int 2021; 99:570-580. [PMID: 33440212 DOI: 10.1016/j.kint.2020.11.010] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 10/23/2020] [Accepted: 11/03/2020] [Indexed: 01/15/2023]
Abstract
Symptomatic multiple myeloma is commonly complicated by acute kidney injury through various mechanisms. The most frequent is the precipitation of monoclonal free light chains with uromodulin in the distal tubules, defining light chain cast nephropathy. Early diagnosis and identification of the cause of acute kidney injury are required for optimizing management and avoiding chronic kidney injury that strongly affects quality of life and patient survival. In light chain cast nephropathy, often manifesting with severe acute kidney injury, renal recovery requires urgent intervention based on vigorous rehydration, correction of precipitating factors, and efficient anti-plasma cell chemotherapy to rapidly reduce the secretion of nephrotoxic free light chains. Currently, the association of the proteasome inhibitor bortezomib with high-dose dexamethasone is the standard regimen in newly diagnosed patients. The addition of another drug such as cyclophosphamide or an immunodulatory agent may improve free light chain response but raises tolerance concerns in frail patients. Further studies are warranted to confirm the role of anti-CD38 monoclonal antibodies, whose efficacy and tolerance have been documented in patients without renal impairment. Despite controversial results from randomized studies, recent data suggest that in patients with light chain cast nephropathy and acute kidney injury requiring dialysis, the combination of chemotherapy with free light chain removal through high-cutoff hemodialysis may increase renal response recovery rates. Kidney biopsy may be helpful in guiding management and assessing renal prognosis that appears to depend on the extent of cast formation and interstitial fibrosis/tubular atrophy. Because of continuous improvement in life expectancy of patients with multiple myeloma, renal transplantation is likely to be increasingly considered in selected candidates.
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Affiliation(s)
- Frank Bridoux
- Department of Nephrology, Dialysis, and Renal Transplantation, CIC INSERM 1402, CHU Poitiers, Poitiers, France; Centre national de référence Amylose AL & autres maladies par dépôts d'immunoglobulines monoclonales, CHU Poitiers, Poitiers, France; Centre National de la Recherche Scientifique UMR CNRS 7276/INSERM U1262, Université de Limoges, Limoges, France.
| | - Nelson Leung
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA; Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA
| | - Mohamed Belmouaz
- Department of Nephrology, Dialysis, and Renal Transplantation, CIC INSERM 1402, CHU Poitiers, Poitiers, France; Centre national de référence Amylose AL & autres maladies par dépôts d'immunoglobulines monoclonales, CHU Poitiers, Poitiers, France
| | - Virginie Royal
- Division of Pathology, Hôpital Maisonneuve-Rosemont, Université de Montréal, Montréal, Canada
| | - Pierre Ronco
- Nephrology Department, Assistance Publique - Hôpitaux de Paris, Hôpital Tenon, Paris, France; Sorbonne Université and Institut National de la Santé Et de la Recherche Médicale (INSERM), Unité Mixte de Recherche S 1135, Paris, France
| | - Samih H Nasr
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Jean Paul Fermand
- Department of Hematology and Immunology, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris, INSERM UMR 1126, Paris, France; Intergroupe Francophone du Myélome (IFM), Paris, France
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19
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Rekhtina IG, Kazarina EV, Stolyarevich ES, Kovrigina AM, Dvirnyk VN, Kulikov SM, Mendeleeva LP. [Morphological and immunohistochemical predictors of renal response to therapy patients with myeloma cast nephropathy and dialysis-dependent acute kidney injury]. TERAPEVT ARKH 2020; 92:63-69. [PMID: 33346446 DOI: 10.26442/00403660.2020.07.000776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Indexed: 11/22/2022]
Abstract
AIM Reveal morphological and immunohistochemical predictors of reversibility of dialysis-dependent acute kidney injury (AKI) in patients with myeloma cast nephropathy (MCN) based on the study of kidney biopsy. MATERIALS AND METHODS Renal pathological findings were studied in 36 patients with MCN and dialysis-dependent stage 3 AKI (AKIN, 2012). The study of biopsy samples was performed by a semi-quantitative and quantitative analysis using computer morphometry. The expression of E-cadherin, vimentin and-smooth muscle actin was determined immunohistochemically in the tubular cells and interstitium. Induction therapy for 26 patients was carried out to bortezomib-based programs; in 10 patients other schemes were used. A comparative analysis of morphological changes in nephrobiopathy depending on the renal response was performed in patients with achieved hematologic remission. RESULTS Improved renal function was observed only in patients with hematologic response to therapy. There were no differences in the number of sclerotic glomeruli, protein casts, the area of inflammatory interstitial infiltration, and the degree of acute tubular damage in patients with and without renal response. In patients with renal response compared with patients without improving renal function, the area of interstitial fibrosis was less (24.9% and 45.9%, respectively;p=0.001), and the area of E-cadherin expression was larger (15.9% and 7.1%, respectively;p=0.006). Interstitial fibrosis of 40% or more and/or the area of expression of E-cadherin less than 10% of the area of tubulo-interstitium have an unfavorable prognostic value in achieving a renal response in MCN. CONCLUSION If the interstitial fibrosis area is 40% or more and the expression area of E-cadherin is less than 10%, the probability of the absence of a renal response is 93.3% (OR=24.5) even when a hematological response to induction therapy is achieved. The number of protein casts, the prevalence of acute tubular damage and inflammatory interstitial infiltration have not prognostic value.
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Affiliation(s)
| | | | - E S Stolyarevich
- Moscow City Nephrology Center, Moscow City Hospital 52.,Yevdokimov Moscow State University of Medicine and Dentistry
| | - A M Kovrigina
- National Research Center for Hematology.,Federal Research Clinical Center of Specialized Types of Medical Care and Medical Technologies
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Yu Y, Song M, Chen C, Du Y, Li C, Han Y, Yan F, Shi Z, Feng S. Bortezomib-Encapsulated CuS/Carbon Dot Nanocomposites for Enhanced Photothermal Therapy via Stabilization of Polyubiquitinated Substrates in the Proteasomal Degradation Pathway. ACS NANO 2020; 14:10688-10703. [PMID: 32790339 DOI: 10.1021/acsnano.0c05332] [Citation(s) in RCA: 70] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Photothermal therapy (PTT) is an emerging therapeutic strategy in the treatment of cancer; however, a critical challenge remains in the rational design of synergistic nanoparticles as a potential photothermal transduction agent that can effectively enhance the therapeutic outcome of PTT for tumor ablation. Herein, we rationally designed, developed, and characterized hollow-structured CuS nanoparticles composited with carbon dots (CuSCDs), which demonstrated excellent photothermal conversion efficiency under a 808 nm laser irradiation with enhanced biocompatibility and reduced toxicity. Following coating with a macrophage membrane hybridized with T7 peptide on the surface of the proteasome inhibitor loaded CuSCD, CuSCDB@MMT7 exhibited targeted specificity to cancer cells with the characteristics of immunity escaping and enhanced transferrin receptor-mediated endocytosis. Predominantly, CuSCDB@MMT7-triggered PTT exhibited the accumulation of the polyubiquitinated tumor suppressor protein that is heat stabilized under NIR induced hyperthermia, facilitating augmented tumor cell apoptosis and the attenuated metastasis. This study provides a proof-of-concept for the proteasome inhibitor-loaded CuS/carbon dot nanocomposite-PTT strategy and highlights a promising therapeutic strategy for realizing enhanced therapeutic outcomes for effective clinical cancer therapy.
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Affiliation(s)
- Ying Yu
- State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, International Joint Research Laboratory of Nano-Micro Architecture Chemistry (NMAC), International Research Center for Chemistry-Medicine Joint Innovation, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, China
| | - Meiyu Song
- State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, International Joint Research Laboratory of Nano-Micro Architecture Chemistry (NMAC), International Research Center for Chemistry-Medicine Joint Innovation, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, China
| | - Cailing Chen
- Advanced Membranes and Porous Materials Center, Physical Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia
| | - Yangyang Du
- State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, International Joint Research Laboratory of Nano-Micro Architecture Chemistry (NMAC), International Research Center for Chemistry-Medicine Joint Innovation, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, China
| | - Chunguang Li
- State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, International Joint Research Laboratory of Nano-Micro Architecture Chemistry (NMAC), International Research Center for Chemistry-Medicine Joint Innovation, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, China
| | - Yu Han
- Advanced Membranes and Porous Materials Center, Physical Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia
| | - Fei Yan
- State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, International Joint Research Laboratory of Nano-Micro Architecture Chemistry (NMAC), International Research Center for Chemistry-Medicine Joint Innovation, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, China
| | - Zhan Shi
- State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, International Joint Research Laboratory of Nano-Micro Architecture Chemistry (NMAC), International Research Center for Chemistry-Medicine Joint Innovation, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, China
| | - Shouhua Feng
- State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, International Joint Research Laboratory of Nano-Micro Architecture Chemistry (NMAC), International Research Center for Chemistry-Medicine Joint Innovation, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, China
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21
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Bridoux F, Arnulf B, Karlin L, Blin N, Rabot N, Macro M, Audard V, Belhadj K, Pegourie B, Gobert P, Cornec Le Gall E, Joly B, Karras A, Jaccard A, Augeul-Meunier K, Manier S, Royer B, Caillot D, Tiab M, Delbes S, Suarez F, Vigneau C, Caillard S, Arakelyan-Laboure N, Roos-Weil D, Chevret S, Fermand JP. Randomized Trial Comparing Double Versus Triple Bortezomib-Based Regimen in Patients With Multiple Myeloma and Acute Kidney Injury Due to Cast Nephropathy. J Clin Oncol 2020; 38:2647-2657. [PMID: 32574117 DOI: 10.1200/jco.20.00298] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
PURPOSE We report a multicenter controlled trial comparing renal recovery and tolerance profile of doublet versus triplet bortezomib-based regimens in patients with initial myeloma cast nephropathy (CN) and acute kidney injury (AKI) without need for dialysis. METHODS After symptomatic measures and high-dose dexamethasone, patients were randomly assigned to receive bortezomib plus dexamethasone (BD), or BD plus cyclophosphamide (C-BD). In patients with < 50% reduction of serum free light chains (sFLCs) after 3 cycles, chemotherapy was reinforced with either cyclophosphamide (BD group) or thalidomide (C-BD group). RESULTS Ninety-two patients were enrolled in each group. At random assignment, characteristics of the 2 groups were similar, including median age (68 years) and serum creatinine level (305.5 and 273.5 µmol/L in BD and C-BD group, respectively). At 3 months, renal response rate (primary end point) was not different (41 v 47 responders in the BD and C-BD groups, respectively; relative risk [RR], 0.87; P = .46). Very good partial response (free light chain reduction ≥ 90%) or more was achieved in 36 and 47 patients, respectively (RR, 0.76; P = .10). After 1 cycle of chemotherapy, 69 in the BD group and 67 patients in the C-BD group had achieved sFLC level ≤ 500 mg/L. Serious adverse events were recorded in 30 and 40 patients, respectively. At 12 months, 19 patients had died (9 in the BD group v 10 in the C-BD group), including 10 (6 in the BD group and 4 in the C-BD group) from myeloma progression and 3 (0 in the BD group and 3 in the C-BD group) from infection. Within median follow-up of 27 months, 43 and 42 patients switched to new therapy, respectively. Overall, 50 patients (24 in the BD group and 26 in the C-BD group) had died. CONCLUSION This randomized study did not show any benefit of C-BD compared with BD on renal recovery of patients with initial CN not requiring dialysis. Adding cyclophosphamide did not sufficiently improve the efficacy-toxicity balance. Patients with myeloma with AKI are fragile, and indication for doublet or triplet regimen should be adapted to frailty.
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Affiliation(s)
- Frank Bridoux
- Department of Nephrology, Centre Hospitalier Universitaire de Poitiers, INSERM CIC 1402, Poitiers University, France.,Centre de référence maladies rares "amylose AL et autres maladies par dépôt d'immunoglobulines monoclonales," Centre Hospitalier Universitaire de Poitiers, Poitiers, France.,CNRS UMR 7276, Université de Limoges, Limoges, France
| | - Bertrand Arnulf
- Department of Hematology and Immunology, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris, INSERM UMR 1126, Paris, France
| | - Lionel Karlin
- Department of Clinical Hematology, Centre Hospitalier Universitaire Lyon Sud, Hospices Civils de Lyon, Pierre-Benite, France
| | - Nicolas Blin
- Department of Hematology, Centre Hospitalier Universitaire de Nantes, Nantes, France
| | - Nolwenn Rabot
- Department of Nephrology and Clinical Immunology, Hôpital Bretonneau, Centre Hospitalier Universitaire de Tours, Tours, France
| | - Margaret Macro
- Department of Hematology, Centre Hospitalier Universitaire de Caen, Caen, France
| | - Vincent Audard
- Department of Nephrology and Renal Transplantation, Hôpital Henri Mondor, Créteil, Assistance Publique-Hôpitaux de Paris, INSERM U955, Université Paris Est Créteil, Créteil, France
| | - Karim Belhadj
- Department of Hematology, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, Université Paris Est Créteil, Créteil, France
| | - Brigitte Pegourie
- Department of Hematology, Centre Hospitalier Universitaire de Grenoble, Grenoble, France
| | - Pierre Gobert
- Department of Nephrology, Centre Hospitalier Avignon, and Clinique Rhône Durance, Avignon, France
| | - Emilie Cornec Le Gall
- Department of Nephrology, Centre Hospitalier Universitaire de Brest, INSERM U1078, Université de Brest, Brest, France
| | - Bertrand Joly
- Department of Hematology, Centre Hospitalier Sud Francilien, Corbeil-Essonnes, France
| | - Alexandre Karras
- Department of Nephrology, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes Sorbonne Paris Cité, Paris, France
| | - Arnaud Jaccard
- Centre de référence maladies rares "amylose AL et autres maladies par dépôt d'immunoglobulines monoclonales," Centre Hospitalier Universitaire de Poitiers, Poitiers, France.,CNRS UMR 7276, Université de Limoges, Limoges, France.,Department of Hematology, Hôpital Dupuytren, Centre Hospitalier Universitaire de Limoges, Université de Limoges, Limoges, France
| | - Karine Augeul-Meunier
- Department of Hematology, Institut de Cancérologie Lucien Neuwirth, Saint-Priest-en-Jarez, France
| | - Salomon Manier
- Department of Hematology, Centre Hospitalier Universitaire de Lille, INSERM UMR-S1172, University of Lille, Lille, France
| | - Bruno Royer
- Department of Hematology, Centre Hospitalier Universitaire d'Amiens, Amiens, France
| | - Denis Caillot
- Department of Clinical Hematology, Centre Hospitalier Universitaire de Dijon, Dijon, France
| | - Mourad Tiab
- Department of Clinical Hematology, Centre Hospitalier de Vendée, La Roche sur Yon, France
| | - Sébastien Delbes
- Department of Nephrology, Centre Hospitalier La Rochelle, La Rochelle, France
| | - Felipe Suarez
- Department of Hematology, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Cécile Vigneau
- Department of Nephrology, Centre Hospitalier Universitaire Pontchaillou, Rennes, France
| | - Sophie Caillard
- Department of Nephrology and Transplantation, Centre Hospitalier Universitaire de Strasbourg, Strasbourg, France
| | - Nina Arakelyan-Laboure
- Department of Clinical Hematology and Cellular Therapy, Centre Hospitalier Régional d'Orléans, Orléans, France
| | - Damien Roos-Weil
- Department of Clinical Hematology, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Sylvie Chevret
- Department of Biostatistics and Medical Information, UMR 1153, ECSTRRA Team, Inserm, Paris Diderot University, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Jean Paul Fermand
- Department of Hematology and Immunology, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris, INSERM UMR 1126, Paris, France
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Twenty-year Follow-up of Histocompatibility Leukocyte Antigen-matched Kidney and Bone Marrow Cotransplantation for Multiple Myeloma With End-stage Renal Disease: Lessons Learned. Transplantation 2020; 103:2366-2372. [PMID: 30801529 DOI: 10.1097/tp.0000000000002669] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND Specific immune tolerance of transplanted organs in association with either transient or sustained lymphohematopoietic chimerism has been demonstrated in several preclinical animal models and clinically in patients who are full donor chimeras after hematopoietic stem cell transplantation and subsequently received kidney transplants from the same donor. Most recently, tolerance induction has been extended to patients in whom chimerism was intentionally induced at the time of kidney transplantation. METHODS Twenty years ago, we reported the first successful histocompatibility leukocyte antigen-matched sibling donor bone marrow and kidney transplant following nonmyeloablative conditioning in a patient with multiple myeloma and end-stage renal disease (ESRD). After 2 decades, she has normal renal function in the absence of ongoing systemic immunosuppressive therapy. Nine patients have subsequently undergone similar treatment for multiple myeloma with ESRD. RESULTS In the initial patient, hematopoietic chimerism was detectable for only 105 days after the transplant. In subsequent patients, chimerism detection ranged from 49 days to >14 years. Nevertheless, a long remission of the myeloma and long-term immunosuppression-free survival of the kidney allograft were achieved in 7 of the 10 patients, 5 of whom currently survive. CONCLUSIONS This initial patient demonstrated the feasibility of performing combined histocompatibility leukocyte antigen-matched, sibling donor bone marrow and kidney transplantation for ESRD due to multiple myeloma. This experience paved the way for extending the initial trial to 9 additional patients with multiple myeloma and ESRD and, more recently, to tolerance induction strategies involving combined bone marrow and kidney transplantation for patients with and without an underlying malignancy.
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Batko K, Malyszko J, Jurczyszyn A, Vesole DH, Gertz MA, Leleu X, Suska A, Krzanowski M, Sułowicz W, Malyszko JS, Krzanowska K. The clinical implication of monoclonal gammopathies: monoclonal gammopathy of undetermined significance and of renal significance. Nephrol Dial Transplant 2020; 34:1440-1452. [PMID: 30169860 DOI: 10.1093/ndt/gfy259] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2018] [Indexed: 12/23/2022] Open
Abstract
Monoclonal gammopathy of renal significance (MGRS) has introduced a new perspective to several well-known disease entities impacting nephrology, haematology and pathology. Given the constantly changing disease spectrum of these entities, it is clinically imperative to establish diagnostic and treatment pathways supported by evidence-based medicine. MGRS is a disease of the kidney, secondary to plasma cell clonal proliferation or immune dysfunction, requiring therapeutic intervention to eradicate the offending clone. To fully understand the disease(s), it is prerequisite to determine the significance of the findings. The diagnostic work up should be extensive due to the wide heterogeneity of clinical presentation, ultimately necessitating kidney biopsy. Particular patient profiles such as AL amyloidosis, which may be diagnosed through biopsies of other tissues/organs, may be an exception. Treatment decisions should be formulated by multi-disciplinary consensus: nephrologists, haematologists and pathologists. The ultimate goal in managing MGRS is eradication of the offending plasma cell clone which requires targeted chemotherapy and, in eligible cases, haematopoietic stem cell transplantation. We present a review of diagnostic procedures, treatment options and advances in the last few years in the management of MGRS in an effort to acquaint specialists with this new face of several older diseases.
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Affiliation(s)
- Krzysztof Batko
- Departament of Nephrology, Jagiellonian University Medical College, Kraków, Poland
| | - Jolanta Malyszko
- Department of Nephrology, Dialysis and Internal Medicine, Warsaw Medical University, Warszawa, Poland
| | - Artur Jurczyszyn
- Departament of Hematology, Jagiellonian University Medical College, Kraków, Poland
| | - David H Vesole
- Myeloma DIvision, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, USA
| | - Morie A Gertz
- Division of Hematology, Mayo Clinic, Rochester, MN, USA
| | - Xavier Leleu
- Service d`Hematologie CHU, Hopital de la Miletrie, Poitiers, France
| | - Anna Suska
- Departament of Hematology, Jagiellonian University Medical College, Kraków, Poland
| | - Marcin Krzanowski
- Departament of Nephrology, Jagiellonian University Medical College, Kraków, Poland
| | - Władysław Sułowicz
- Departament of Nephrology, Jagiellonian University Medical College, Kraków, Poland
| | - Jacek S Malyszko
- 1st Department of Nephrology, Medical University, Bialystok, Poland
| | - Katarzyna Krzanowska
- Departament of Nephrology, Jagiellonian University Medical College, Kraków, Poland
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24
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Malhotra V, Pandey A, Agarwal D, Rathore V, Sharma G, Nowal S, Beniwal P, Jhorawat R, Sharma S. Short Term Renal Outcome of Bortezomib Based Therapy in Patients with Multiple Myeloma Requiring Dialysis. Indian J Nephrol 2020; 30:213-214. [PMID: 33013077 PMCID: PMC7470190 DOI: 10.4103/ijn.ijn_229_18] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
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25
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Cejalvo MJ, Legarda M, Abella E, Cabezudo E, Encinas C, García‐Feria A, Gironella M, Iñigo B, Martín J, Ribas P, Ruíz MÁ, González Y, Vicuña I, Ramírez Á, Fernández P, Rubia J. Single‐agent daratumumab in patients with relapsed and refractory multiple myeloma requiring dialysis: results of a Spanish retrospective, multicentre study. Br J Haematol 2019; 190:e289-e292. [DOI: 10.1111/bjh.16286] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Affiliation(s)
- María J. Cejalvo
- Department of Hematology University Hospital Doctor Peset Valencia Spain
| | - Mario Legarda
- Department of Hematology University Hospital Doctor Peset Valencia Spain
| | - Eugenia Abella
- Department of Hematology Hospital del Mar Barcelona Spain
| | - Elena Cabezudo
- Department of Hematology Hospital Sant Joan de Déu Barcelona Spain
| | | | | | | | - Belén Iñigo
- Department of Hematology Hospital Clínico San Carlos Madrid Spain
| | - Jesús Martín
- Department of Hematology Hospital Virgen del Rocío Sevilla Spain
| | - Paz Ribas
- Department of Hematology University Hospital Doctor Peset Valencia Spain
| | - Mª Ángeles Ruíz
- Department of Hematology Hospital Francesc Borja Gandía Spain
| | - Yolanda González
- Department of Hematology Instituto Catalán de Oncología Girona Spain
| | - Isabel Vicuña
- Department of Hematology Hospital La Princesa Madrid Spain
| | - Ángel Ramírez
- Department of Hematology Hospital Central de Asturias Oviedo Spain
| | | | - Javier Rubia
- Department of Hematology University Hospital Doctor Peset Valencia Spain
- Internal Medicine School of Medicine and Dentistry Catholic University of Valencia Valencia Spain
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26
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Semochkin SV, Zhelnova EI, Misyurina EN, Maryin DS, Ushakova AI, Karimova EA, Baryakh EA, Tolstykh TN, Mavrina ES, Yurova EV, Cherkasova AV, Grishina EY, Gagloeva DE, Yatskov KV, Kotenko ON, Lysenko MA. CLINICAL IMPORTANCE OF RENAL RECOVER ON OUTCOMES OF NEWLY DIAGNOSED MULTIPLE MYELOMA PATIENTS WITH SEVERE AND DIALYSIS-DEPENDENT KIDNEY FAILURE. RUSSIAN JOURNAL OF HEMATOLOGY AND TRANSFUSIOLOGY 2019. [DOI: 10.35754/0234-5730-2019-64-3-283-296] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Introduction. Kidney damage at the onset of multiple myeloma (MM) is observed in 20–40 % of patients, which requires renal replacement therapy in 2–4 % of cases. Deterioration in kidney function is associated with frequent complications and a decline in the quality of life, as well as carries a high risk of early death.Aim. To analyze the treatment of patients first diagnosed with MM, complicated by severe and dialysis-dependent renal failure.Materials and methods. 62 MM patients with a glomerular filtration rate of <30 ml/min /1.73 m2 participated in a retrospective study (11.2014–11.2017) with the following inclusion criteria: the concentration of free light chains in blood serum being >500 mg/l and the selective nature of proteinuria. Diagnosed AL-amyloidosis served as the exclusion criterion. Depending on the need for haemodialysis, patients were divided into two groups: (I) those not requiring it (n = 16) and (II) dialysis-dependent patients (n = 46).Results. The induction therapy included the following bortezomib-containing regimens: VCD — 41 (66.1 %), PAD — 2 (3.2 %), VD — 12 (19.4 %) and VMP — 7 (11.3 %). High-dose consolidation along with autologous hematopoietic stem cell transplantation was performed in 10 patients (16.1 %). The overall rate of anti-myeloma response in the groups came to 64.3 % (I) and 85.3 % (II) (p = 0.047), including complete and strong complete remissions in 14.3 % (I) and 14.7 % (II) of cases. The renal response was achieved by 57.2 % and 23.5 % (p = 0.032) of patients from the first and second groups, respectively. With a median follow-up of 32.1 months, throughout the entire cohort the median of progression-free survival (PFS) amounted to 14.5 months, with a 3-year PFS of 27.4 ± 6.6 %; whereas the median of overall survival (OS) came to 33.6 months, with a 3-year OS of 41.5 ± 7.7 %. There are no differences between the compared groups in terms of the survival rates. In the examined patients (n = 48), the achievement of any renal response was associated with an improvement in the 3-year PFS — 61.1 ± 11.5 % versus 17.7 ± 7.7 % (p = 0.045) — and 3-year OS — 72,2 ± 10.6 % versus 38.1 ± 10.4 % (p= 0.069). The time elapsed between the first haemodialysis procedure and the onset of anti-myeloma chemotherapy served as the predictor value of the renal response. In the group of patients who achieved a renal response, the average time came to 8.6 (95 % confidence interval of 3.5–13.7) days, as compared to 42.5 (12.6–72.5) days for patients without a renal response (p = 0.045).Conclusion. The use of bortezomib-based regimens provides a high frequency of antitumour responses with a probability of stopping dialysis in 23.5 % of dialysis-dependent patients. Possible reasons for the low frequency of renal response include the late diagnosis of MM as a cause of kidney damage, as well as the lack of access to new anti-myeloma drugs if the induction therapy needs to be changed.
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Affiliation(s)
- S. V. Semochkin
- Moscow City Hospital #52;
Pirogov Russian National Research Medical University
| | | | | | | | | | | | | | | | | | - E. V. Yurova
- Pirogov Russian National Research Medical University
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Song J, Jiang F, Liu H, Ding K, Ren Y, Li L, Wang G, Shao Z, Fu R. Effect factors related to a high probability of hemodialysis independence in newly diagnosed multiple myeloma patients requiring hemodialysis. J Clin Lab Anal 2019; 34:e23057. [PMID: 31663630 PMCID: PMC7031559 DOI: 10.1002/jcla.23057] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Revised: 09/10/2019] [Accepted: 09/11/2019] [Indexed: 12/22/2022] Open
Abstract
Background Renal failure is a severe complication of symptomatic myeloma, related to higher mortality. Recovery from dialysis dependence can lead to enormous survival benefits. We investigated the effect factors for probability of dialysis independence. Methods Retrospective data on 45 newly diagnosed MM (NDMM) patients with serious renal impairment and requiring hemodialysis were analyzed. The statistical methods including logistic regression analysis, Kaplan‐Meier survival curves, the log‐rank test and the Cox proportional hazards model for survival analysis were used in our study. Results Twenty‐two of the 45 patients, who were on hemodialysis at diagnosis, became dialysis independence. In the logistic regression analysis, serum level of β2‐microglobulin, kidney disease history, involved free light chain, and achieving at least VGPR were significantly associated with reversibility from dialysis dependence. In addition, achieving hemodialysis discontinuation was related to better survival. The multivariate analyses demonstrated that reversibility from dialysis dependence, proteinuria < 3.5 g/24 h, and achieving at least VGPR were significantly associated with OS among NDMM patients requiring hemodialysis. Conclusion Lower serum level of β2‐microglobulin and lower level of free light chain at diagnosis, achieving at least VGPR, and shorter kidney disease history are related to a high probability of dialysis independence in NDMM patients with serious renal failure requiring dialysis.
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Affiliation(s)
- Jia Song
- Department of Hematology, Tianjin Medical University General Hospital, Tianjin, China
| | - Fengjuan Jiang
- Department of Hematology, Tianjin Medical University General Hospital, Tianjin, China
| | - Hui Liu
- Department of Hematology, Tianjin Medical University General Hospital, Tianjin, China
| | - Kai Ding
- Department of Hematology, Tianjin Medical University General Hospital, Tianjin, China
| | - Yue Ren
- Department of Hematology, Tianjin Medical University General Hospital, Tianjin, China
| | - Lijuan Li
- Department of Hematology, Tianjin Medical University General Hospital, Tianjin, China
| | - Guojin Wang
- Department of Hematology, Tianjin Medical University General Hospital, Tianjin, China
| | - Zonghong Shao
- Department of Hematology, Tianjin Medical University General Hospital, Tianjin, China
| | - Rong Fu
- Department of Hematology, Tianjin Medical University General Hospital, Tianjin, China
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Rosner MH, Perazella MA. Acute kidney injury in the patient with cancer. Kidney Res Clin Pract 2019; 38:295-308. [PMID: 31284363 PMCID: PMC6727896 DOI: 10.23876/j.krcp.19.042] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 05/05/2019] [Accepted: 05/13/2019] [Indexed: 02/06/2023] Open
Abstract
Dramatic advances in the care of patients with cancer have led to significant improvement in outcomes and survival. However, renal manifestations of the underlying cancer as well as the effects of anti-neoplastic therapies leave patients with significant morbidity and chronic kidney disease risks. The most common renal manifestations associated with cancer include acute kidney injury (AKI) in the setting of multiple myeloma, tumor lysis syndrome, post-hematopoietic stem cell therapy, and AKI associated with chemotherapy. Knowledge of specific risk factors, modification of risk and careful attention to rapid AKI diagnosis are critical for improving outcomes.
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Affiliation(s)
- Mitchell H Rosner
- Division of Nephrology, University of Virginia Health System, Charlottesville, VA, USA
| | - Mark A Perazella
- Department of Internal Medicine, Section of Nephrology, Yale University School of Medicine, New Haven, CT, USA
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29
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Muñoz-Bermúdez R, Abella E, Zuccarino F, Masclans JR, Nolla-Salas J. Successfully non-surgical management of flail chest as first manifestation of multiple myeloma: A case report. World J Crit Care Med 2019. [DOI: 10.5492/wjcc.v8.i5.59] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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30
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Muñoz-Bermúdez R, Abella E, Zuccarino F, Masclans JR, Nolla-Salas J. Successfully non-surgical management of flail chest as first manifestation of multiple myeloma: A case report. World J Crit Care Med 2019; 8:82-86. [PMID: 31559147 PMCID: PMC6753394 DOI: 10.5492/wjccm.v8.i5.82] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Revised: 07/23/2019] [Accepted: 08/16/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Multiple myeloma is a malignant neoplasm of the bone marrow characterized by neoplastic proliferation of monoclonal plasma cells with a high relationship with destructive bone disease. We present a case of a patient diagnosed with multiple myeloma and sternal fracture in association with multiple bilateral rib fractures and thoracic kyphosis, who developed a severe acute respiratory failure, thus complicating the initial presentation of multiple myeloma. We discuss the therapeutic implications of this uncommon presentation.
CASE SUMMARY A 56-year-old man presented to Hematological Department after he had been experiencing worsening back pain over the last five months, with easy fatigability and progressive weight loss. He had no history of previous trauma. The chemical blood tests were compatible with a diagnosis of multiple myeloma. A radiographic bone survey of all major bones revealed, in addition to multiple bilateral rib fractures, a sternal fracture and compression fracture at T9, T10, T11 and L1 vertebrae. Subcutaneous fat biopsy was positive for amyloid. We started treatment with bortezomib and dexamethasone. After 24 h of treatment, he presented dyspnea secondary to flail chest. He required urgent intubation and ventilatory support being transferred to intensive care unit for further management. The patient remained connected to mechanical ventilation (positive pressure) as treatment which stabilized the thorax. A second cycle of bortezomib plus dexamethasone was started and analgesia was optimized. The condition of the patient improved, as evidenced by callus formation on successive computed tomography scans. The patient was taken off the ventilator one month later, and he was extubated successfully, being able to breathe unaided without paradoxical motion.
CONCLUSION This case highlights the importance of combination between bortezomib and dexamethasone to induce remission of multiple myeloma and the initiation of positive airway pressure with mechanical ventilation to stabilize chest wall to solve the respiratory failure. This combined approach allowed to obtain a quick and complete resolution of the clinical situation.
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Affiliation(s)
| | - Eugenia Abella
- Department of Hematology, Hospital del Mar, Barcelona 08003, Spain
| | - Flavio Zuccarino
- Department of Radiology, Hospital del Mar, Barcelona 08003, Spain
| | | | - Juan Nolla-Salas
- Department of Critical Care, Hospital del Mar, Barcelona 08003, Spain
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31
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Cao Q, Qi H, Yao L, Liu Q. Monoclonal gammopathy of renal significance: clinical manifestation, pathogenic characteristic and treatment. Panminerva Med 2019; 62:38-53. [PMID: 30848114 DOI: 10.23736/s0031-0808.19.03609-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Monoclonal gammopathy of renal significance (MGRS) is a group of renal disorders caused by a monoclonal immunoglobulin (MIg) secreted by a dangerous plasmatic/B-cell clone hyperplasia through MIg deposition or dysfunction of complement pathway, with increasing risk of progress to end stage renal disease (ESRD) and the underlying hematologic malignancy. The combination of renal biopsy, complete laboratory examination and bone marrow biopsy is an indispensable diagnostic tool for MGRS to identify accurately and unequivocally the pathogenic monoclonal MIg and provide guidance to treatment. Treatment of MGRS is composed of conventional therapy, chemotherapy, and stem cell transplantation to target the underlying clone and eliminate the noxious MIg on the basis of clinical data of some retrospective studies and a small amount of prospective trial. In addition, it is worthwhile point out assessment of therapeutic effect is significantly relevant for renal and overall prognosis. Thus, by comprehensively analyzing the clinical manifestations and pathogenic characteristic of MGRS, early recognition and prompt treatment can improve the prognosis and prevent post-translation recurrence with multidisciplinary cooperation.
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Affiliation(s)
- Qin Cao
- Department of Gastroenterology, The First Hospital of China Medical University, Shenyang, China
| | - Huimeng Qi
- Department of General Practice, The First Hospital of China Medical University, Shenyang, China
| | - Li Yao
- Department of Nephrology, The First Hospital of China Medical University, Shenyang, China
| | - Qiang Liu
- Department of Nephrology, The First Hospital of China Medical University, Shenyang, China -
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32
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Dialysis independence following single-agent daratumumab in refractory myeloma with renal failure. Ir J Med Sci 2018; 188:1079-1080. [PMID: 30569372 DOI: 10.1007/s11845-018-1951-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Accepted: 12/10/2018] [Indexed: 10/27/2022]
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33
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Carfilzomib vs bortezomib in patients with multiple myeloma and renal failure: a subgroup analysis of ENDEAVOR. Blood 2018; 133:147-155. [PMID: 30478094 DOI: 10.1182/blood-2018-06-860015] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Accepted: 10/27/2018] [Indexed: 12/20/2022] Open
Abstract
In ENDEAVOR, carfilzomib (56 mg/m2) and dexamethasone (Kd56) demonstrated longer progression-free survival (PFS) over bortezomib and dexamethasone (Vd) in patients with relapsed/refractory multiple myeloma (RRMM). Here we evaluated Kd56 vs Vd by baseline renal function in a post hoc exploratory subgroup analysis. The intent-to-treat population included 929 patients (creatinine clearance [CrCL] ≥15 to <50 mL/min, n = 85 and n = 99; CrCL 50 to <80 mL/min, n = 186 and n = 177; and CrCL ≥80 mL/min, n = 193 and n = 189 for Kd56 and Vd arms, respectively). In these respective subgroups, median PFS was 14.9 vs 6.5 months (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.320-0.757), 18.6 vs 9.4 months (HR, 0.48; 95% CI, 0.351-0.652), and not reached (NR) vs 12.2 months (HR, 0.60; 95% CI, 0.434-0.827) for those receiving Kd56 vs Vd, respectively; median overall survival (OS) was 42.1 vs 23.7 months (HR, 0.66; 95% CI, 0.443-0.989), 42.5 vs 32.8 months (HR, 0.83; 95% CI, 0.626-1.104), and NR vs 42.3 months (HR, 0.75; 95% CI, 0.554-1.009). Complete renal response (ie, CrCL improvement to ≥60 mL/min in any 2 consecutive visits if baseline CrCL <50 mL/min) rates were 15.3% (95% CI, 8.4-24.7) and 14.1% (95% CI, 8.0-22.6) for those receiving Kd56 vs Vd, respectively. In a combined Kd56 and Vd analysis, complete renal responders had longer median PFS (14.1 vs 9.4 months; HR, 0.805; 95% CI, 0.438-1.481) and OS (35.3 vs 29.7 months; HR, 0.91; 95% CI, 0.524-1.577) vs nonresponders. Grade ≥3 adverse event rates in the respective subgroups were 87.1% vs 79.4%, 84.4% vs 71.8%, and 77.1% vs 65.9% for those receiving Kd56 vs Vd, respectively. Thus, Kd56 demonstrated PFS and OS improvements over Vd in RRMM patients regardless of their baseline renal function. The ENDEAVOR trial was registered at www.clinicaltrials.gov as #NCT01568866.
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Waszczuk-Gajda A, Lewandowski Z, Drozd-Sokołowska J, Boguradzki P, Dybko J, Wróbel T, Basak GW, Jurczyszyn A, Mądry K, Snarski E, Frączak E, Charliński G, Feliksbrot-Bratosiewicz M, Król M, Matuszkiewicz-Rowińska J, Klinger M, Krajewska M, Augustyniak-Bartosik H, Kościelska M, Rusicka P, Dwilewicz-Trojaczek J, Wiktor Jędrzejczak W. Autologous peripheral blood stem cell transplantation in dialysis-dependent multiple myeloma patients-DAUTOS Study of the Polish Myeloma Study Group. Eur J Haematol 2018; 101:475-485. [DOI: 10.1111/ejh.13101] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/15/2018] [Indexed: 12/21/2022]
Affiliation(s)
- Anna Waszczuk-Gajda
- Department of Haematology, Oncology and Internal Diseases; Warsaw Medical University; Warsaw Poland
| | - Zbigniew Lewandowski
- Department of Epidemiology and Biostatistics; Warsaw Medical University; Warsaw Poland
| | - Joanna Drozd-Sokołowska
- Department of Haematology, Oncology and Internal Diseases; Warsaw Medical University; Warsaw Poland
| | - Piotr Boguradzki
- Department of Haematology, Oncology and Internal Diseases; Warsaw Medical University; Warsaw Poland
| | - Jarosław Dybko
- Department and Clinic of Haematology, Blood Neoplasms and Bone Marrow Transplantation; Wroclaw Medical University; Warsaw Poland
| | - Tomasz Wróbel
- Department and Clinic of Haematology, Blood Neoplasms and Bone Marrow Transplantation; Wroclaw Medical University; Warsaw Poland
| | - Grzegorz Władysław Basak
- Department of Haematology, Oncology and Internal Diseases; Warsaw Medical University; Warsaw Poland
| | - Artur Jurczyszyn
- Department of Haematology; Jagiellonian University; Kraków Poland
| | - Krzysztof Mądry
- Department of Haematology, Oncology and Internal Diseases; Warsaw Medical University; Warsaw Poland
| | - Emilian Snarski
- Department of Haematology, Oncology and Internal Diseases; Warsaw Medical University; Warsaw Poland
| | - Ewa Frączak
- Department and Clinic of Haematology, Blood Neoplasms and Bone Marrow Transplantation; Wroclaw Medical University; Warsaw Poland
| | - Grzegorz Charliński
- Department of Haematology, Oncology and Internal Diseases; Warsaw Medical University; Warsaw Poland
- Department of Haematology; Nicolaus Copernicus Specialist Municipal Hospital; Toruń Poland
| | | | - Małgorzata Król
- Department of Haematology, Oncology and Internal Diseases; Warsaw Medical University; Warsaw Poland
| | | | - Marian Klinger
- Department of Nephrology and Transplantation Medicine; Wroclaw Medical University; Wrocław Poland
| | - Magdalena Krajewska
- Department of Nephrology and Transplantation Medicine; Wroclaw Medical University; Wrocław Poland
| | | | - Małgorzata Kościelska
- Department of Nephrology and Internal Diseases; Medical University of Warsaw; Warsaw Poland
| | - Patrycja Rusicka
- Department of Haematology, Oncology and Internal Diseases; Warsaw Medical University; Warsaw Poland
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Acute kidney injury and electrolyte disorders in the critically ill patient with cancer. Curr Opin Crit Care 2018; 23:475-483. [PMID: 28953555 DOI: 10.1097/mcc.0000000000000450] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
PURPOSE OF REVIEW Patients with cancer increasingly make up a significant proportion of patients receiving care in the intensive care unit (ICU). Acute kidney injury and cancer-associated electrolyte disorders are encountered in many of these patients and can significantly impact both short-term and long-term outcomes. RECENT FINDINGS Advances in chemotherapeutic regimens as well as in our understanding of cancer-associated kidney disease highlight the need for specialized knowledge of the unique causes and therapies required in this subset of critically ill patients. This is especially the case as targeted cancer therapies may have off-target effects that need to be recognized in a timely manner. SUMMARY This review outlines key knowledge areas for critical care physicians and nephrologists caring for patients with cancer and associated kidney issues such as acute kidney injury and electrolyte disorders. Specifically, understanding kidney-specific effects of new chemotherapeutic approaches is outlined, and provides an up-to-date compendium of these effects.
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Snozek CLH, Kinard TN, Adamski J. Rapid reduction of extremely high kappa free light chains in a patient with myeloma cast nephropathy. J Clin Apher 2018; 33:439-443. [PMID: 29427353 DOI: 10.1002/jca.21619] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2017] [Revised: 10/26/2017] [Accepted: 01/30/2018] [Indexed: 01/01/2023]
Abstract
This report describes a patient with light chain myeloma and acute renal injury. Serum kappa free light chain (FLC) was extremely elevated, >33,000 mg/dL. Treatment with therapeutic plasma exchange (TPE) started day 2 for biopsy-confirmed cast nephropathy. Bortezomib-containing chemotherapy was initiated on day 5, and hemodialysis for tumor lysis syndrome on day 7. TPE alone decreased kappa FLC >70% by day 5, indicating direct FLC removal was successful in this patient. A total of 25 TPE procedures were performed in a 31-day hospitalization. Hemodialysis was discontinued after 3 months, and the patient's renal function and kappa FLC remain stable. Although the use of TPE for FLC removal is controversial, recent evidence supports its use as adjuvant therapy for acute renal injury secondary to myeloma cast nephropathy. TPE can be effective for rapidly reducing FLC; however, several TPE procedures might be required to reduce the risk of hemodialysis dependency.
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Affiliation(s)
- Christine L H Snozek
- Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Arizona 85054
| | - Theresa N Kinard
- Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Arizona 85054
| | - Jill Adamski
- Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Arizona 85054
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Wu T, Zhou J, Wang C, Wang B, Zhang S, Bai H. Bortezomib overcomes the negative prognostic impact of renal impairment in a newly diagnosed elderly patient with multiple myeloma: A case report. Oncol Lett 2018; 14:7318-7322. [PMID: 29344169 PMCID: PMC5754884 DOI: 10.3892/ol.2017.7151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2016] [Accepted: 07/14/2017] [Indexed: 11/22/2022] Open
Abstract
Multiple myeloma (MM) is a common B-cell hematological malignancy in the clinic. Bortezomib is the first-in-class proteasome inhibitor that has been approved for the treatment of patients with MM in the bone marrow. The present study report the case of an 83-year-old man who showed marked weakness, fatigue and a poor appetite. The patient was admitted to the Department of Nephrology due to severe renal impairment (RI). Immunofixation electrophoresis indicated a λ light chain-positive status. There were 19.2% plasmablasts and proplasmacytes in the bone marrow. Positivity for the cell surface markers cluster of differentiation (CD)13, CD33, CD38 and human leukocyte antigen-antigen D-related was detected by flow cytometry. The patient was diagnosed with MM, λ light chain type, stage IIIB, and received bortezomib and dexamethasone regimen chemotherapy. RI was improved following the chemotherapy, and plasmablasts and proplasmacytes were almost eliminated. The Hb level was maintained at ~90 g/l. Overall, the present case report suggests that bortezomib may be safe and effective for elderly patients, even those >80 years of age, with severe RI.
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Affiliation(s)
- Tao Wu
- Department of Hematology, Lanzhou General Hospital, Lanzhou Command, Lanzhou, Gansu 730050, P.R. China
| | - Jinmao Zhou
- Department of Hematology, Lanzhou General Hospital, Lanzhou Command, Lanzhou, Gansu 730050, P.R. China
| | - Cunbang Wang
- Department of Hematology, Lanzhou General Hospital, Lanzhou Command, Lanzhou, Gansu 730050, P.R. China
| | - Binbin Wang
- Department of Hematology, Lanzhou General Hospital, Lanzhou Command, Lanzhou, Gansu 730050, P.R. China
| | - Shuting Zhang
- Department of Hematology, Lanzhou General Hospital, Lanzhou Command, Lanzhou, Gansu 730050, P.R. China
| | - Hai Bai
- Department of Hematology, Lanzhou General Hospital, Lanzhou Command, Lanzhou, Gansu 730050, P.R. China
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Premuzic V, Batinic J, Roncevic P, Basic-Jukic N, Nemet D, Jelakovic B. Role of Plasmapheresis in the Management of Acute Kidney Injury in Patients With Multiple Myeloma: Should We Abandon It? Ther Apher Dial 2017; 22:79-86. [DOI: 10.1111/1744-9987.12606] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2017] [Revised: 06/23/2017] [Accepted: 07/24/2017] [Indexed: 11/30/2022]
Affiliation(s)
- Vedran Premuzic
- Department of Nephrology, Hypertension, Dialysis and Transplantation; University Hospital Centre Zagreb; Zagreb Croatia
| | - Josip Batinic
- Department of Haematology; University Hospital Centre Zagreb; Zagreb Croatia
| | - Pavle Roncevic
- Department of Haematology; University Hospital Centre Zagreb; Zagreb Croatia
| | - Nikolina Basic-Jukic
- Department of Nephrology, Hypertension, Dialysis and Transplantation; University Hospital Centre Zagreb; Zagreb Croatia
| | - Damir Nemet
- Department of Haematology; University Hospital Centre Zagreb; Zagreb Croatia
| | - Bojan Jelakovic
- Department of Nephrology, Hypertension, Dialysis and Transplantation; University Hospital Centre Zagreb; Zagreb Croatia
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Bridoux F, Carron PL, Pegourie B, Alamartine E, Augeul-Meunier K, Karras A, Joly B, Peraldi MN, Arnulf B, Vigneau C, Lamy T, Wynckel A, Kolb B, Royer B, Rabot N, Benboubker L, Combe C, Jaccard A, Moulin B, Knebelmann B, Chevret S, Fermand JP. Effect of High-Cutoff Hemodialysis vs Conventional Hemodialysis on Hemodialysis Independence Among Patients With Myeloma Cast Nephropathy: A Randomized Clinical Trial. JAMA 2017; 318:2099-2110. [PMID: 29209721 PMCID: PMC5820717 DOI: 10.1001/jama.2017.17924] [Citation(s) in RCA: 91] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Accepted: 11/06/2017] [Indexed: 11/14/2022]
Abstract
Importance Cast nephropathy is the main cause of acute kidney injury in multiple myeloma and persistent reduction in kidney function strongly affects prognosis. Strategies to rapidly remove nephrotoxic serum-free light chains combined with novel antimyeloma agents have not been evaluated prospectively. Objective To compare the hemodialysis independence rate among patients newly diagnosed with myeloma cast nephropathy treated with hemodialysis using a high-cutoff dialyzer (with very large membrane pores and high permeability to immunoglobulin light chains) or a conventional high-flux dialyzer (with small pores and lower permeability). Design, Setting, and Participants Randomized clinical trial involving 98 patients with biopsy-proven myeloma cast nephropathy requiring hemodialysis treated at 48 French centers between July 2011 and June 2016; the final date of follow-up was June 29, 2016. Interventions Intensive hemodialysis (eight 5-hour sessions over 10 days) with either a high-cutoff dialyzer (46 patients) or a conventional high-flux dialyzer (48 patients). All patients received the same chemotherapy regimen of bortezomib and dexamethasone. Main Outcomes and Measures Primary end point was hemodialysis independence at 3 months; secondary end points: hemodialysis independence rates at 6 and 12 months, hemodialysis- and chemotherapy-related adverse events, and death. Results Among 98 randomized patients, 94 (96%) (median age, 68.8 years [interquartile range, 61.2-75.3 years]; 45% women) were included in the modified intent-to-treat analysis. The hemodialysis independence rate at 3 months was 41.3% (n = 19) in the high-cutoff hemodialysis group vs 33.3% (n = 16) in the conventional hemodialysis group (between-group difference, 8.0% [95% CI, -12.0% to 27.9%], P = .42); at 6 months, the rate was 56.5% (n = 26) vs 35.4% (n = 17), respectively (between-group difference, 21.1% [95% CI, 0.9% to 41.3%], P = .04); and at 12 months, the rate was 60.9% (n = 28) vs 37.5% (n = 18) (between-group difference, 23.4% [95% CI, 3.2% to 43.5%], P = .02). The incidence of hemodialysis-related adverse events was 43% in the high-cutoff hemodialysis group vs 39% in the conventional hemodialysis group; chemotherapy-related serious adverse events, 39% vs 37%, respectively; and at 12 months, 9 patients vs 10 patients died. Conclusions and Relevance Among patients with myeloma cast nephropathy treated with a bortezomib-based chemotherapy regimen, the use of high-cutoff hemodialysis compared with conventional hemodialysis did not result in a statistically significant difference in hemodialysis independence at 3 months. However, the study may have been underpowered to identify an early clinically important difference. Trial Registration clinicaltrials.gov Identifier: NCT01208818.
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Affiliation(s)
- Frank Bridoux
- Department of Nephrology, Institut National de la Santé et de la Recherche Médicale, Centre d’Investigation Clinique 1402, Centre Hospitalier Universitaire, Poitiers, France
- Centre de Référence Maladies Rares, Poitiers, France
- Centre National de la Recherche Scientifique, Unite Mixte de Recherche 7276, Université de Limoges, Limoges, France
| | - Pierre-Louis Carron
- Department of Nephrology, Centre Hospitalier Universitaire, Grenoble, France
| | - Brigitte Pegourie
- Department of Hematology, Centre Hospitalier Universitaire, Grenoble, France
| | - Eric Alamartine
- Department of Nephrology, Centre Hospitalier Universitaire, Saint-Etienne, France
| | | | - Alexandre Karras
- Department of Nephrology, Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, Paris, France
| | - Bertrand Joly
- Department of Hematology, Centre Hospitalier Sud Francilien, Corbeil-Essonnes, France
| | - Marie-Noëlle Peraldi
- Department of Nephrology, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, Paris, France
| | - Bertrand Arnulf
- Department of Hematology and Immunology, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1126, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, Paris, France
| | - Cécile Vigneau
- Department of Nephrology, Centre Hospitalier Universitaire, Rennes, France
| | - Thierry Lamy
- Department of Hematology, Centre Hospitalier Universitaire, Rennes, France
| | - Alain Wynckel
- Department of Nephrology, Centre Hospitalier Universitaire, Reims, France
| | - Brigitte Kolb
- Department of Hematology, Centre Hospitalier Universitaire, Reims, France
| | - Bruno Royer
- Department of Hematology, Centre Hospitalier Universitaire, Amiens, France
| | - Nolwenn Rabot
- Department of Nephrology, Centre Hospitalier Universitaire, Tours, France
| | - Lotfi Benboubker
- Department of Hematology, Centre Hospitalier Universitaire, Tours, France
| | - Christian Combe
- Department of Nephrology, Centre Hospitalier Universitaire, Bordeaux, France
| | - Arnaud Jaccard
- Centre de Référence Maladies Rares, Poitiers, France
- Centre National de la Recherche Scientifique, Unite Mixte de Recherche 7276, Université de Limoges, Limoges, France
- Department of Hematology, Centre Hospitalier Universitaire, Limoges, France
| | - Bruno Moulin
- Department of Nephrology, Centre Hospitalier Universitaire, Strasbourg, France
| | - Bertrand Knebelmann
- Department of Nephrology, Hôpital Necker, Assistance Publique Hôpitaux de Paris, Paris, France
| | - Sylvie Chevret
- Department of Biostatistics and Medical Information, Institut National de la Santé et de la Recherche Médicale, Unite Mixte de Recherche 1153 (ECSTRA Team), Paris Diderot University, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, Paris, France
| | - Jean-Paul Fermand
- Department of Hematology and Immunology, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1126, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, Paris, France
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Ailawadhi S, Frank RD, Advani P, Swaika A, Temkit M, Menghani R, Sharma M, Meghji Z, Paulus S, Khera N, Hashmi SK, Paulus A, Kakar TS, Hodge DO, Colibaseanu DT, Vizzini MR, Roy V, Colon-Otero G, Chanan-Khan AA. Racial disparity in utilization of therapeutic modalities among multiple myeloma patients: a SEER-medicare analysis. Cancer Med 2017; 6:2876-2885. [PMID: 29105343 PMCID: PMC5727310 DOI: 10.1002/cam4.1246] [Citation(s) in RCA: 70] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2017] [Revised: 09/29/2017] [Accepted: 10/02/2017] [Indexed: 01/22/2023] Open
Abstract
Outcomes have improved considerably in multiple myeloma (MM), but disparities among racial-ethnic groups exist. Differences in utilization of novel therapeutics are likely contributing factors. We explored such differences from the SEER-Medicare database. A utilization analysis of lenalidomide, thalidomide, bortezomib, and stem cell transplant (SCT) was performed for patients diagnosed with MM between 2007 and 2009, including use over time, use by race, time-dependent trends for each racial subgroup, and survival analysis. A total of 5338 MM patients were included with median 2.4-year follow-up. Within the first year of MM diagnosis, utilization of lenalidomide, bortezomib, SCT, and more than one novel agent increased over time while utilization of thalidomide decreased. There was significantly lower utilization of lenalidomide among African-Americans (P < 0.01), higher thalidomide use among Hispanics and Asians (P < 0.01), and lower bortezomib use among Asians (P < 0.01). Hispanics had the highest median number of days to first dose of bortezomib (P = 0.02) and the lowest utilization of SCT (P < 0.01). Hispanics and Asians were the only groups without notable increases in lenalidomide and bortezomib use, respectively. SCT utilization increased over time for all except African-Americans. SCT use within the first year after diagnosis was associated with better overall survival (HR 0.52; 95% CI: 0.4-0.68), while bortezomib use was associated with inferior survival (HR 1.14; 95% CI 1.02-1.28). We noted considerable variability in MM therapeutics utilization with seeming inequity for racial-ethnic minorities. These trends should be considered to eliminate drug access and utilization disparities and achieve equitable benefit of therapeutic advances across all races.
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Affiliation(s)
- Sikander Ailawadhi
- Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, Florida
| | - Ryan D Frank
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
| | - Pooja Advani
- Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, Florida
| | - Abhisek Swaika
- Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, Florida
| | - M'hamed Temkit
- Division of Biomedical Statistics, Mayo Clinic, Scottsdale, Arizona
| | - Richa Menghani
- Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, Florida
| | - Mayank Sharma
- Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, Florida
| | - Zahara Meghji
- Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, Florida
| | - Shumail Paulus
- Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, Florida
| | - Nandita Khera
- Division of Hematology and Medical Oncology, Mayo Clinic, Scottsdale, Arizona
| | | | - Aneel Paulus
- Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, Florida
| | - Tanya S Kakar
- Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, Florida
| | - David O Hodge
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
| | | | | | - Vivek Roy
- Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, Florida
| | - Gerardo Colon-Otero
- Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, Florida
| | - Asher A Chanan-Khan
- Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, Florida
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Bortezomib pharmacokinetics in tumor response and peripheral neuropathy in multiple myeloma patients receiving bortezomib-containing therapy. Anticancer Drugs 2017; 28:660-668. [PMID: 28430745 DOI: 10.1097/cad.0000000000000506] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The usefulness of pharmacokinetics of bortezomib for multiple myeloma (MM) with respect to the maximum response to bortezomib and bortezomib-induced peripheral neuropathy (BIPN) development was studied. Maximum response to subcutaneous bortezomib therapy and BIPN occurrence for the first 12 weeks of treatment in 35 MM patients treated by bortezomib-dexamethasone (VD) and bortezomib-melphalan-prednisone (VMP) were evaluated. On day 1 of cycle 1, seven whole-blood samples were collected for 3 h after dosing completion to obtain the maximum plasma concentration and area under the time-concentration curve during 3 h postdose (AUC0-3) in each patient. A total of 35 patients with complete data were analyzed and the overall response rate was 91.4%. Complete response (CR) was observed in 42.9% patients. The maximum plasma concentration (Cmax) was significant for the CR rate in two different models [full model: odds ratio (OR)=1.092; P=0.038, final model: OR=1.081; P=0.038]. In addition, Cmax was associated with a progression-free survival advantage. Overall, 48.6% of patients developed BIPN including peripheral sensory neuropathy and neuralgia. The VMP-treated patients had a higher risk compared with the VD-treated patients (OR=21.662; P=0.029). Cmax had a tendency to affect the occurrence of BIPN (≥grade 2) (OR=1.064; P=0.092). In real-world clinical practice using bortezomib for MM patients, Cmax among pharmacokinetic factors significantly affected the achievement of CR. The VMP-treated patients showed vulnerability to BIPN, suggesting the necessity for more careful monitoring.
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Sens F, Chaintreuil D, Jolivot A, Guebre-Egziabher F, Robinson P, Karlin L, Bridoux F, Juillard L. Effectiveness of IHD with Adsorptive PMMA Membrane in Myeloma Cast Nephropathy: A Cohort Study. Am J Nephrol 2017; 46:355-363. [PMID: 29017155 DOI: 10.1159/000481461] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Accepted: 09/07/2017] [Indexed: 01/13/2023]
Abstract
BACKGROUND In patients with cast nephropathy and acute kidney injury (AKI) requiring dialysis, the reduction of serum free light chains (FLC) using chemotherapy and intensive hemodialysis (IHD) with a high cut-off filter may improve renal and patient outcomes. We evaluated the effectiveness of a combination of chemotherapy and IHD with an adsorbent polymethylmethacrylate membrane (IHD-PMMA) on renal recovery and survival. METHODS A single-center retrospective cohort-study was conducted. Between 2007 and 2014, patients with dialysis-dependent acute cast nephropathy treated with chemotherapy and IHD-PMMA were included. Patients had six 6-h hemodialysis sessions a week, until predialysis serum FLC fell below 200 mg/L, for a maximum of 3 weeks. Primary outcomes were renal recovery, defined as dialysis independence, and survival. RESULTS Seventeen patients were included, all with stage 3 AKI. All received chemotherapy, mostly based on bortezomib and steroids (88%). Twelve patients (71%) achieved renal recovery, usually within 60 days (92%). At 3 months, the overall hematological response rate was 57%; hematological response was maintained for at least 2 years in 86% of responders. At 6, 12, and 24 months, 76, 75, and 62% of patients were alive, respectively. Higher reduction in involved FLC by day 12 (p = 0.022) and day 21 (p = 0.003) was associated with renal recovery. Patients with FLC reduction rate >50% by day 21 experienced a lower mortality (hazard ratio 0.10, 95% CI 0.02-0.63). CONCLUSION In patients with dialysis-dependent myeloma cast nephropathy, early FLC removal by IHD-PMMA combined with chemotherapy was associated with high rates of renal recovery and survival.
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Affiliation(s)
- Florence Sens
- Hospices Civils de Lyon, Department of Nephrology, Edouard Herriot Hospital, Lyon, France
- Lyon 1 Claude Bernard University, Villeurbanne, France
- Hospices Civils de Lyon, Department of Medical Information Evaluation and Research, Lyon, France
- FCRIN INI-CRCT, Nancy, France
| | - Déborah Chaintreuil
- Hospices Civils de Lyon, Department of Nephrology, Edouard Herriot Hospital, Lyon, France
| | - Anne Jolivot
- Hospices Civils de Lyon, Department of Nephrology, Edouard Herriot Hospital, Lyon, France
| | - Fitsum Guebre-Egziabher
- Grenoble University Hospital, Department of Nephrology, Dialysis and Transplantation, La Tronche, France
| | - Philip Robinson
- Hospices Civils de Lyon, Direction de la Recherche Clinique et de l'Innovation, Lyon, France
| | - Lionel Karlin
- Hospices Civils de Lyon, Department of Medical Information Evaluation and Research, Lyon, France
- Hospices Civils de Lyon, Department of Hematology, Centre Hospitalier Lyon Sud, Lyon, France
| | - Frank Bridoux
- Poitiers University Hospital, Department of Nephrology, Dialysis and Transplantation, Poitiers, France
| | - Laurent Juillard
- Hospices Civils de Lyon, Department of Nephrology, Edouard Herriot Hospital, Lyon, France
- Hospices Civils de Lyon, Department of Medical Information Evaluation and Research, Lyon, France
- Poitiers University Hospital, Department of Nephrology, Dialysis and Transplantation, Poitiers, France
- OPeRa, CARMEN, Lyon 1 Claude Bernard University, Villeurbanne, France
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Faiman B. Disease and Symptom Care: A Focus on Specific Needs of Patients With Multiple Myeloma. Clin J Oncol Nurs 2017; 21:3-6. [PMID: 28945733 DOI: 10.1188/17.cjon.s5.3-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Patients with multiple myeloma (MM) often deal with short- and long-term side effects of the treatment and disease sequelae. Reasons for inadequately managed symptoms are multifactorial (e.g., the patient may fear treatment interruption, the clinician does not assess or address the symptoms) and can affect patients' ability to remain on the recommended treatment. This article provides background surrounding this supplement's development and describes the importance of symptom assessment and management.
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Faiman B, Doss D, Colson K, Mangan P, King T, Tariman J, Board A. Renal, GI, and Peripheral Nerves: Evidence-Based Recommendations for the Management of Symptoms and Care for Patients With Multiple Myeloma. Clin J Oncol Nurs 2017; 21:19-36. [DOI: 10.1188/17.cjon.s5.19-36] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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Pawlyn C, Gay F, Larocca A, Roy V, Ailawadhi S. Nuances in the Management of Older People With Multiple Myeloma. Curr Hematol Malig Rep 2017; 11:241-51. [PMID: 27038805 DOI: 10.1007/s11899-016-0323-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
Multiple myeloma is a disease of the elderly, with about a third of patients at diagnosis older than 75 years of age. Yet, the population of elderly patients is heterogeneous: older patients are more likely to have comorbidities and frailties complicating both their initial diagnosis and subsequent management, but these are not consistent across the group. Furthermore, patients with comorbidities and frailty are generally underrepresented in clinical trials. Despite the survival of myeloma patients increasing following the introduction of novel agents, older patients continue to have worse outcomes with increased treatment-related toxicity. Treatment tolerability is not defined by age alone, rather a combination of age, physical function, cognitive function, and comorbidities. These factors all influence patients' tolerability of treatment and therefore treatment efficacy and should also be considered when reviewing the results of clinical trials. It is the nuances of determining how these factors interact that should influence initial treatment and ongoing management decisions and these will be discussed here.
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Affiliation(s)
- Charlotte Pawlyn
- The Institute of Cancer Research, 15, Cotswold Rd, Sutton, Surrey, SM2 5NG, UK.,The Royal Marsden Hospital NHS Foundation Trust, London, UK
| | - Francesca Gay
- Dipartimento di Oncologia ed Ematologia, SC Ematologia 1, A.O. Citta' della Salute e della Scienza di Torino, P.O. Molinette, C.so Bramante 88/90, 10126, Torino, Italy.,Myeloma Unit, Division of Hematology, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, University of Torino, Turin, Italy
| | - Alessandra Larocca
- Dipartimento di Oncologia ed Ematologia, SC Ematologia 1, A.O. Citta' della Salute e della Scienza di Torino, P.O. Molinette, C.so Bramante 88/90, 10126, Torino, Italy.,Myeloma Unit, Division of Hematology, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, University of Torino, Turin, Italy
| | - Vivek Roy
- Division of Hematology/Oncology, Department of Medicine, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, FL, 32224, USA
| | - Sikander Ailawadhi
- Division of Hematology/Oncology, Department of Medicine, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
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Gammapatías monoclonales de significado renal. Nefrologia 2017; 37:465-477. [DOI: 10.1016/j.nefro.2017.03.012] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2016] [Revised: 03/13/2017] [Accepted: 03/14/2017] [Indexed: 01/02/2023] Open
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Affiliation(s)
- Mitchell H Rosner
- From the Division of Nephrology, University of Virginia Health System, Charlottesville (M.H.R.); and the Section of Nephrology, Yale University School of Medicine, New Haven, and the Veterans Affairs Medical Center, West Haven - both in Connecticut (M.A.P.)
| | - Mark A Perazella
- From the Division of Nephrology, University of Virginia Health System, Charlottesville (M.H.R.); and the Section of Nephrology, Yale University School of Medicine, New Haven, and the Veterans Affairs Medical Center, West Haven - both in Connecticut (M.A.P.)
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48
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Mohan M, Matin A, Davies FE. Update on the optimal use of bortezomib in the treatment of multiple myeloma. Cancer Manag Res 2017; 9:51-63. [PMID: 28280389 PMCID: PMC5338851 DOI: 10.2147/cmar.s105163] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
The proteasome inhibitor (PI) "bortezomib" has now been in routine clinical practice for over a decade. It is now considered an important backbone therapy for all stages of the disease, and data continue to grow to support its use in newly diagnosed patients, relapsed and relapsed/refractory disease, maintenance therapy, high risk, and renal failure. Much has been learnt about the most clinically effective way of delivering therapy, with patients often benefiting more from a triplet bortezomib combination compared to a doublet combination. It is well tolerated and can be administered in the outpatient setting with manageable toxicity. The key to good results is managing side effects so that patients remain on therapy with minimal interruptions. Therefore, proactive management of peripheral neuropathy and thrombocytopenia is advised using dose delay and reduction strategies. The recent introduction of second- and third-generation PIs with different chemical and biological properties has resulted in a plethora of new clinical studies and has confirmed the ongoing role of this class of drugs in future myeloma therapy.
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Affiliation(s)
- Meera Mohan
- Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Aasiya Matin
- Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Faith E Davies
- Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA
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49
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Nakaya A, Fujita S, Satake A, Nakanishi T, Azuma Y, Tsubokura Y, Hotta M, Yoshimura H, Ishii K, Ito T, Nomura S. Impact of CRAB Symptoms in Survival of Patients with Symptomatic Myeloma in Novel Agent Era. Hematol Rep 2017; 9:6887. [PMID: 28286629 PMCID: PMC5337823 DOI: 10.4081/hr.2017.6887] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2016] [Accepted: 12/28/2016] [Indexed: 12/03/2022] Open
Abstract
The acronym CRAB summarizes the most typical clinical manifestations of multiple myeloma, these being hypercalcemia, renal failure, anemia, and bone disease. CRAB can be used to distinguish between active, symptomatic multiple myeloma and monoclonal gammopathy of undermined significance or smoldering myeloma. The distinction is relevant not only for classification and diagnosis but also for therapy. CRAB factors influence the prognosis of multiple myeloma. However, it is unclear whether the presence of CRAB factors has an influence on the prognosis of myeloma treated with novel agents. In the current study, patients with hypercalcemia and bone disease showed a significantly worse prognosis, whereas anemia and renal failure showed no difference in survival. Novel agents used for treatment of patients with renal failure suggested a favorable outcome compared with conventional therapy. Bone disease was the most common factor and may have the strongest prognostic value in symptomatic myeloma patients using novel agents.
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Affiliation(s)
- Aya Nakaya
- First Department of Internal Medicine, Kansai Medical University , Hirakata, Japan
| | - Shinya Fujita
- First Department of Internal Medicine, Kansai Medical University , Hirakata, Japan
| | - Atsushi Satake
- First Department of Internal Medicine, Kansai Medical University , Hirakata, Japan
| | - Takahisa Nakanishi
- First Department of Internal Medicine, Kansai Medical University , Hirakata, Japan
| | - Yoshiko Azuma
- First Department of Internal Medicine, Kansai Medical University , Hirakata, Japan
| | - Yukie Tsubokura
- First Department of Internal Medicine, Kansai Medical University , Hirakata, Japan
| | - Masaaki Hotta
- First Department of Internal Medicine, Kansai Medical University , Hirakata, Japan
| | - Hideaki Yoshimura
- First Department of Internal Medicine, Kansai Medical University , Hirakata, Japan
| | - Kazuyoshi Ishii
- First Department of Internal Medicine, Kansai Medical University , Hirakata, Japan
| | - Tomoki Ito
- First Department of Internal Medicine, Kansai Medical University , Hirakata, Japan
| | - Shosaku Nomura
- First Department of Internal Medicine, Kansai Medical University , Hirakata, Japan
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50
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Finkel KW, Cohen EP, Shirali A, Abudayyeh A. Paraprotein-Related Kidney Disease: Evaluation and Treatment of Myeloma Cast Nephropathy. Clin J Am Soc Nephrol 2016; 11:2273-2279. [PMID: 27526708 PMCID: PMC5142056 DOI: 10.2215/cjn.01640216] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Nearly 50% of patients with multiple myeloma develop renal disease, most commonly from AKI caused by cast nephropathy. Development of AKI is associated with poor 1-year survival and reduces the therapeutic options available to patients. There is a great need for more effective therapies. Cast nephropathy is caused by the interaction and aggregation of filtered free light chains and Tamm-Horsfall protein causing intratubular obstruction and damage. The key to treating cast nephropathy is rapid lowering of free light chains, because this correlates with renal recovery. Newer chemotherapy agents rapidly lower free light chains and have been referred to as renoprotective. There is additional great interest in using extracorporeal therapies to remove serum free light chains. Small trials initially showed benefit of therapeutic plasma exchange to improve renal outcomes in cast nephropathy, but a large randomized trial of therapeutic plasma exchange failed to show benefit. A newer technique is extended high-cutoff hemodialysis. This modality uses a high molecular weight cutoff filter to remove free light chains. To date, trials of high-cutoff hemodialysis use in patients with cast nephropathy have been encouraging. However, there are no randomized trials showing the benefit of high-cutoff hemodialysis when used in addition to newer chemotherapeutic regimens. Until these studies are available, high-cutoff hemodialysis cannot be recommended as standard of care.
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Affiliation(s)
- Kevin W. Finkel
- Department of Medicine, Division of Renal Diseases and Hypertension, University of Texas Health Science Center at Houston McGovern Medical School, Houston, Texas
- Department of General Internal Medicine, Nephrology Section, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Eric P. Cohen
- Nephrology Section, Baltimore Veterans Affairs Medical Center, University of Maryland School of Medicine, Baltimore, Maryland; and
| | - Anushree Shirali
- Department of Medicine, Section of Nephrology, Yale University Medical School, New Haven, Connecticut
| | - Ala Abudayyeh
- Department of General Internal Medicine, Nephrology Section, University of Texas MD Anderson Cancer Center, Houston, Texas
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