Haivas, Claudia-Denise

Background. The use of immune checkpoint inhibitors (ICIs) in kidney transplant recipients (KTR) for cancer treatment is limited by concerns of allograft rejection and uncertain oncologic efficacy. Methods. We conducted a single-center retrospective study of KTR with unresectable or metastatic malignancies treated between 2018 and 2025. The primary study cohort included 33 patients treated with ICI, whose outcomes were compared with 20 matched KTR treated with non-ICI systemic chemotherapy (SC). Results. KTR treated with ICI achieved an objective response rate of 36.4% (12/33) versus 30.0% (6/20) with SC, and a clinical benefit rate of 54.5% (18/33) versus 35.0% (7/20); neither difference was statistically significant (objective response rate P = 0.77; clinical benefit rate P = 0.27). Disease progression occurred in 81.8% of ICI-treated patients and 95.0% of SC-treated patients ( P = 0.23), and death because of cancer progression occurred in 63.6% and 75.0%, respectively ( P = 0.58). Median progression-free survival was 7.3 mo (95% confidence interval [CI], 4.3-10.8 mo) in the ICI group versus 4.1 mo (95% CI, 2.8-6.3 mo) in the SC group (log-rank P = 0.156). Median overall survival was 15.1 mo (95% CI, 7.6-37.3 mo) with ICI versus 8.7 mo (95% CI, 4.9-14.8 mo) with SC (log-rank P = 0.079). Posttreatment allograft rejection occurred in 12.1% of ICI-treated patients and 0.0% of SC-treated patients ( P = 0.29), with irreversible graft loss in 3.0%. Grade ≥2 immune-related adverse events occurred in 12.1% of ICI-treated patients, and no treatment-related deaths were observed. Conclusions. ICI therapy was associated with a trend toward longer overall survival when compared with SC and with a low rate of rejection and allograft loss.

Abstract Background: Kidney transplant recipients (KTRs) have a markedly elevated risk of aggressive malignancies, yet the use of immune checkpoint inhibitors (ICIs) in this population remains limited by concerns for allograft rejection and the absence of prospective evidence. We evaluated real-world antitumor activity, graft safety, and immunosuppression-related outcomes of ICI therapy in KTRs with advanced cancers. Methods: We retrospectively analyzed 57 KTRs with locally advanced unresectable or metastatic malignancies treated between 2018-2025 at a single tertiary center. Thirty-three received ICIs and 24 received non-ICI systemic therapy. Outcomes included objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS), overall survival from diagnosis (OSd), overall survival from treatment initiation (OSt), acute allograft rejection, and immune-related adverse events (irAEs). Tumor response was assessed by RECIST v1.1. Results: ICI-treated patients achieved higher ORR (40.0% vs 26.1%) and CBR (60.0% vs 33.3%) compared with non-ICI therapy. Median OSd was 35.8 vs 23.3 months, and median PFS was 4.3 vs 3.5 months (both not statistically significant). Median OSt was significantly longer with ICIs (15.1 vs 7.9 months; p=0.012). Acute rejection occurred in 12.1% of ICI-treated patients (3% irreversible) versus 4.2% with systemic therapy; rejection events were heterogeneous in timing (3 weeks-14 months) and largely responsive to pulse-dose corticosteroids. IrAEs occurred in 27.3% of ICI patients, with grade ≥2 events in 12.1%, and no treatment-related deaths. In the cutaneous squamous cell carcinoma (cSCC) subgroup (n=33), ICI therapy produced an ORR of 47.4% and CBR of 63.2%, with trends toward improved survival relative to controls. Conclusions: ICIs produced clinically meaningful antitumor activity in KTRs, particularly in cSCC, with a manageable rate of allograft rejection under carefully tailored immunosuppression. Despite higher historical concerns, irreversible graft loss was uncommon. These findings support the feasibility of ICI therapy in selected transplant recipients and highlight the importance of immunosuppression strategy in balancing antitumor efficacy and graft safety. Prospective, biomarker-integrated studies are needed to define optimal immunosuppression during PD-1 blockade in this high-risk population. Citation Format: Ali Rezazadeh Roudkoli, Elena Barbir, Shahin Kavousi, Mohamed A. Aboelatta, Claudia-Denise Haivas, Byron H. Smith, Aleksandra Kukla, Arkadiusz Z. Dudek. Immune checkpoint inhibitor therapy in kidney transplant recipients: Real-world outcomes of antitumor activity and graft rejection risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6544.