Published online Apr 6, 2021. doi: 10.12998/wjcc.v9.i10.2394
Peer-review started: December 15, 2020
First decision: December 28, 2020
Revised: January 6, 2021
Accepted: January 28, 2021
Article in press: January 28, 2021
Published online: April 6, 2021
Processing time: 104 Days and 20.9 Hours
Chimeric antigen receptor T cell (CART) therapy has benefited many refractory lymphoma patients, but some patients experience poor effects. Previous studies have shown that programmed cell death protein-1 (PD-1) inhibitors can improve and prolong the therapeutic effect of CAR-T cell treatment.
A 61-year-old male presented with 15-d history of diarrhea and lower-limb edema. A large mass was detected in the pelvis, and pathology indicated non-Hodgkin diffuse large B-cell lymphoma. After three cycles of the R-CHOP chemotherapeutic regimen, the patient showed three subcutaneous nodules under the left armpit and both sides of the cervical spine. Pathological examination of the nodules indicated DLBCL again. The patient was diagnosed with relapsed and refractory diffuse large B-cell lymphoma. We recommended CAR-T cell treatment. Before treatment, the patient’s T cell function and expression of immune detection points were tested. Expression of PD-1 was obviously increased (52.7%) on cluster of differentiation (CD)3+ T cells. The PD-1 inhibitor (3 mg/kg) was infused prior to lymphodepleting chemotherapy with fludarabine and cyclophosphamide. CAR-CD19 T cells of 3 × 106/kg and CAR-CD22 T cells 1 × 106/kg were infused, respectively. The therapeutic effect was significant, and the deoxyribonucleic acid copy numbers of CAR-CD19 T cells and CAR-CD22 T cells were stable. Presently, the patient has been disease-free for more than 12 mo.
This case suggests that the combination of PD-1 inhibitors and CAR-T cells improved therapeutic efficacy in B-cell lymphoma.
Core Tip: The mechanism of early loss of chimeric antigen receptor T (CAR-T) cells may be the depletion of activated T cells due to stimulation of the immune checkpoint pathway [such as programmed cell death protein-1 (PD-1)] of lymphoma cells. Immune checkpoints have a critical role in the immune system. This case suggests that PD-1 expression may affect the therapeutic effect of CAR-T cell therapy, and combination CAR-T cells and a PD-1 inhibitor may be a viable treatment option for relapsed and refractory non-Hodgkin lymphoma.