Retrospective analysis of the safety and efficacy of immune checkpoint inhibitors (CPI) among patients (pts) with pre-existing autoimmune disorders (AD) and renal cell carcinoma (RCC) or urothelial carcinoma (UC).

person Nieves Martinez Chanza Jules Bordet Institute, Brussels, Belgium info_outline Nieves Martinez Chanza, Wanling Xie, Majd Issa, Hannah Elizabeth Dzimitrowicz, Abhishek Tripathi, Benoit Beuselinck, Elaine Tat Lam, Yousef Zakharia, Rana R. McKay, Sumit Shah, Amir Mortazavi, Michael Roger Harrison, Toni K. Choueiri, Lauren Christine Harshman

Authors person Nieves Martinez Chanza Jules Bordet Institute, Brussels, Belgium info_outline Nieves Martinez Chanza, Wanling Xie, Majd Issa, Hannah Elizabeth Dzimitrowicz, Abhishek Tripathi, Benoit Beuselinck, Elaine Tat Lam, Yousef Zakharia, Rana R. McKay, Sumit Shah, Amir Mortazavi, Michael Roger Harrison, Toni K. Choueiri, Lauren Christine Harshman Organizations Jules Bordet Institute, Brussels, Belgium, Dana-Farber Cancer Institute, Boston, MA, Ohio State University - James Cancer Hospital Solove Research Institute, Columbus, OH, Yale School of Medicine, New Haven, CT, University of Oklahoma, Stephenson Cancer Center, Oklahoma City, OK, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium, University of Colorado Cancer Center, Denver, CO, University of Iowa Holden Comprehensive Cancer Center, Iowa City, IA, University of California, San Diego, San Diego, CA, Stanford Univ, San Francisco, CA, Arthur G. James Cancer Hospital, Ohio State University Wexner Medical Center, Columbus, OH, Duke Cancer Institute, Duke University Medical Center, Durham, NC, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA Abstract Disclosures Research Funding Other Background: RCC and UC pts with clinically significant AD were generally excluded from CPI trials due to potential AD exacerbation. Thus, the safety and clinical activity of CPI in AD pts are not well characterized. Methods: We retrospectively collected data from RCC and UC pts with AD treated with CPI at 9 centers. Adverse events (AEs) were assessed using CTCAEv5 criteria. Objective response rate (ORR) was assessed by RECIST principles. Overall survival (OS) was estimated by Kaplan Meier. Results: Of 103 pts (57 RCC & 46 UC) with a broad spectrum of AD such as psoriasis (22%), thyroiditis (20%), rheumatoid arthritis (13%), polymyalgia rheumatica (8%), inflammatory bowel disease (6%), multiple sclerosis (3%) and lupus (3%), most received CPI as 1 st or 2 nd line (77% RCC, 93% UC) and anti-PD-1/L1 monotherapy (65% RCC, 98% UC). At CPI start, 36 had clinically active AD (all grade 1-2) and 4(11%) requiring systemic immunosuppression. AD exacerbations occurred in 37% (n = 38); most frequent: arthritis (12% RCC, 24% UC), rash (11% RCC, 9% UC). New onset immune related (ir) AEs occurred in 36% (n = 37); most frequent: colitis (12% RCC, 4% UC), rash (11% RCC, 9% UC), hypothyroid (each 7%), nephritis (7% UC). Table details timing and management. Median followup was 12.5 (1-52) mos for RCC and 14.5 (1-53) mos for UC. Median time on CPI was 6 mos (1-36) RCC and 4 mos (0.5-40) UC. At data cutoff, 39 RCC & 36 UC had discontinued CPI; 16% for toxicity. ORR was 31% for RCC and 35% for UC. 1 yr-OS rate was 74% (95%CI 58-84) for RCC and 60% (95%CI 43-74) for UC. Conclusions: AD exacerbations or new irAEs occurred in 37% and 36% respectively and were generally manageable. Only a minority required CPI cessation due to toxicity. AD EXACERBATIONS NEW irAEs RCC N = 57 UC N = 46 RCC N = 57 UC N = 46 N (%) 18 (32) 20 (43) 21 (37) 16 (35) 38 (37) 37 (36) Grade (n, %) 1/2 13(23) 14(30) 14(25) 9(20) 3/4 2(4) 4(9) 7(12) 5(11) Unkn 3(5) 2(4) - 2(4) Med Time CPI to AE, days (range) 69 (25-315) 32 (3-368) 48 (2-305) 120 (12-443) Systemic steroid (n, %) 5 (28) 12 (60) 11 (52) 9 (56) DMARDs (n, %) 1 (6) 2 (10) 0 (0) 0(0) CPI stopped for irAE (n, %) Temporary 3 (17) 5 (25) 8 (38) 6 (36) Permanent 2 (11) 4 (20) 3 (14) 3 (19)