Relative carcinogenicity of tacrolimus vs mycophenolate after solid organ transplantation and its implications for liver transplant care

Table 1 Inclusion and exclusion criteria utilised for literature search strategy

Inclusion criteria	Exclusion criteria
Involve human solid organ transplant recipients	Presents risk data on only one of the immunosuppressant medications
Independent malignancy risk analysis related to both immunosuppressants mycophenolic acid and tacrolimus	Does not specify type of immunosuppression
Contains a group of participants exposed to tacrolimus or mycophenolic acid, exclusive of the other	Mean follow up less than one year (given the slow growing nature of malignancy)
Greater than 100 participants	Not published in English
Greater than 5 cases of malignancy	Full text not available
Randomised controlled trials and observational studies	Systematic reviews and meta-analyses

Table 2 Summary of studies comparing tacrolimus to mycophenolic acid in solid organ transplantation

Ref.	Transplant era	Organ	n	De novo malignancy	Time to malignancy (median)	TAC vs no TAC (OR/HR/IRR)	MPA vs no MPA (OR/HR/IRR)
Van Leeuwen et al[50], 2009	1982 to 2003	Kidney	8162	203 lip SCC; 121 lip SCC of the lower vermillion in first transplant)	6.1 yr	SCC of the lower vermillion of lip during first transplant [IRR: 2.07, 95%CI: 0.45-9.50 (P = 0.35)]	SCC of the lower vermillion of lip during first transplant [IRR: 0.85, 95%CI: 0.28-2.60 (P = 0.77)]
Caillard et al[51], 2012	1998 to 2007	Kidney ± pancreas	21351	181 PTLD; 43 graft PTLD	Not specified	Any PTLD [aHR: 0.66, 95%CI: 0.36-1.22 (P = 0.19)]; Graft PTLD [HR: 0.33, 95%CI: 0.16-0.68 (P = 0.003)a]	Any PTLD [aHR: 1.22, 95%CI: 0.74-2.02 (P = 0.44)]; Graft PTLD [HR: 0.44, 95%CI: 0.23-0.86 (P = 0.015)a]
Hsiao et al[47], 2014	2000 to 2008	Kidney	642	54 non-cutaneous malignancy	3.9 yr	HR: 1.99, 95%CI: 0.66-6.00 (P = 0.22)	HR: 1.00, 95%CI: 0.40-2.45 (P = 0.99)
Coghill et al[49], 2016	1995 to 2010	Kidney ± pancreas, and heart	2004	170 SCC	9.0 yr	Single SCC (OR: 1.11, 95%CI: 0.48-2.60)	Single SCC (OR: 0.52, 95%CI: 0.32-0.84a)
Yeh et al[46], 2020	1997 to 2011	Liver, kidney, and heart	7852	612 cutaneous and non-cutaneous malignancy	Not specified	cHR (heart): 0.6, 95%CI: 0.1-2.7; cHR (kidney): 1.5, 95%CI: 0.8-2.6; aHR (liver): 0.6, 95%CI: 0.2-1.7	cHR (heart): 1.6, 95%CI: 0.7-3.3; aHR (kidney): 1.5, 95%CI: 1.2-1.8 (P < 0.001)a; cHR (liver): 1.5, 95%CI: 0.9-2.5
Gibson et al[48], 2021	2010 to 2018	Liver, kidney ± pancreas, heart, and lung	2852	242 cutaneous malignancy	4.7 yr	IRR: 0.83, 95%CI: 0.55-1.25 (P = 0.37)	IRR: 0.78, 95%CI: 0.54-1.12 (P = 0.18)

^aP < 0.05.

aHR: Adjusted hazard ratio; cHR: Crude hazard ratio; HR: Hazard ratio; IRR: Incidence rate ratio; MPA: Mycophenolic acid; OR: Odds ratio; PTLD: Post-transplant lymphoproliferative disorder; SCC: Squamous cell carcinoma; TAC: Tacrolimus; 95%CI: 95% confidence interval.