Cancer
Cancer risk, all-cause mortality, and graft failure/retransplantation with belatacept use among kidney transplant recipients in the United States Shyfuddin Ahmed* Shyfuddin Ahmed Karena Volesky-Avellaneda Kelly J Yu Jon Snyder Judy R Rees Fiona Zwald Ajay Israni Charles F Lynch Baozhen Qiao Christopher D Blosser Ruth M. Pfeiffer Eric A. Engels
Kidney transplant recipients (KTRs) have elevated cancer risk due to use of immunosuppressive medications. Belatacept (BEL), a less nephrotoxic CTLA4 agonist, was introduced for maintenance immunosuppression in 2011, but is contraindicated in EBV-seronegative KTRs due to risk of posttransplant lymphoproliferative disorder (PTLD). Evidence on cancer risk and other outcomes with BEL is limited.
We used linked US transplant and cancer registry data on KTRs treated with BEL (n=1,705) or tacrolimus (TAC, n=42,756). KTRs were followed from transplant until earliest of first cancer diagnosis, death, or graft failure/retransplantation (GF/RT) during 2011-19. We fit multivariable Cox regression models to compare cancer incidence between BEL and TAC users. We also assessed risk of basal cell carcinoma (BCC), skin squamous cell carcinoma (SCC), PTLD, death and GF/RT using the US transplant registry data (2,715 BEL, 68,626 TAC users).
Overall cancer incidence was 11.66 and 11.55 per 1000 person-years in BEL and TAC users, respectively. We did not find increased risk with BEL use for cancer overall (hazard ratio [HR] 1.03, 95%CI 0.78-1.36) and 11 individual cancer types, or death (1.10, 0.98-1.24) (see Table). BEL was associated with increased risk of stomach cancer (HR 4.73, 95%CI 1.30-17.18) and colorectal cancer (2.87, 1.16-7.07), based on small numbers (Table). BEL was not associated with risk of SCC, BCC, PTLD, or mortality overall and was associated with decreased risk of GF/RT (HR 0.88, 95%CI 0.76-1.02). Notably, BEL was associated with increased all-cause mortality in EBV-seronegative KTRs (HR 1.92, 95% 1.21-3.04).
This large study provides reassurance that BEL does not increase overall cancer risk compared to TAC among KTRs. The findings for stomach and colorectal cancers require further study. We observed a benefit in terms of GF/RT overall but an adverse association of BEL with death in EBV-seronegative KTRs, for whom this medication is contraindicated.
