Immune Checkpoint Inhibitors in Kidney Transplant Recipients: A French Multicenter Retrospective Cohort Study

Abstract

Background: Kidney transplant recipients (KTRs) are at elevated risk of malignancy. Data on the safety and efficacy of immune checkpoint inhibitors (ICIs) in this population remain limited. We aimed to reassess the benefit-risk profile of ICI therapy in KTRs using a multicenter cohort, in the recent era.

Methods: We conducted a retrospective cohort study of all KTRs treated with ICIs for advanced or metastatic cancer, across 6 transplant centers. We evaluated cancer response, acute rejection (AR) incidence, graft survival, and patient survival.

Results: From 2015 to 2024, 34 KTRs were analyzed. The most common cancers were cutaneous (56%) and non-small cell lung cancer (32%). Pembrolizumab was the most used ICI (53%). The objective response rate was 38%, with a median progression-free survival of 5.5 mo and an overall survival of 10.7 mo. Biopsy-proven AR occurred in 26.5% of patients, at a median time of 52 d after ICI start. All rejection episodes involved T cells, and one-third showed additional humoral features. No clinical predictors of AR were identified. Among all patients, 29% had a favorable outcome (tumor response without ICI-induced graft loss), 12% experienced a tumor response with graft loss, 59% had progression disease without graft loss, and 3% experienced the worst outcome (progression disease with graft loss).

Conclusions: Our study suggests that ICI therapy is a viable option for KTRs with poor-prognosis cancers, demonstrating a 38% tumor response rate and a lower incidence of graft loss (15%) compared with previously reported rates. Prospective studies are needed to optimize the use of ICI in KTRs.

FIGURE 1.

Evolution of immunosuppression at 3 different times: cancer diagnosis, ICI initiation, and last follow-up. Results are expressed as percentage of patients under each immunosuppressive treatment. Patients who lost their renal transplant after ICI therapy were not included in the analysis of immunosuppression at last follow-up. CNI, calcineurin inhibitor; ICI, immune checkpoint inhibitor; LFU, last follow-up; mTORi, mammalian target of rapamycin inhibitor.

FIGURE 2.

Overall survival of the cohort (A) and cancer-specific survival (B) of ICI-treated KTRs. PFS (C) and cancer-specific PFS (D) of ICI-treated KTRs. ICI, immune checkpoint inhibitor; KTR, kidney transplant recipient; PFS, progression-free survival.

FIGURE 3.

Death-censored graft survival (A) and overall patient and graft survival (B) of ICI-treated KTRs. Impact of acute rejection on death-censored graft survival (C) and overall patient and graft survival (D) after ICI. ICI, immune checkpoint inhibitor; KTR, kidney transplant recipient.

FIGURE 4.

renal allograft and cancer outcomes after ICI therapy in the present cohort study. Adapted from Ferrándiz-Pulido et al. CR, complete response; ICI, immune checkpoint inhibitor; PD, progression disease; PR, partial response.