Patients with renal cell carcinoma (RCC) or urothelial carcinoma (UC) with clinically significant autoimmune disorders (AD) are commonly excluded from trials of immune checkpoint inhibitors (CPI) due to potential AD exacerbation. As a result, there are few available data on the safety and clinical mechanism of CPI in patients with AD.
In a retrospective data analysis, researchers, led by Nieves Martinez Chanza, MD, of the Jules Bordet Institute, Brussels, Belgium, collected data from nine centers on patients with RCC and UC with AD who were treated with CPI. Common Terminology Criteria for Adverse Events (version 5.0) (CTCAEv5) criteria were used to assess adverse events (AEs); Response Evaluation Criteria in Solid Tumors (RECIST) principles were used to assess objective response rate (ORR); and Kaplan Meier models were used to estimate overall survival. Results were reported during a poster session at the ASCO 2019 Annual Meeting in a poster titled 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 or Urothelial Carcinoma (UC).
A total of 103 patients (57 with RCC and 46 with UC) exhibited a broad spectrum of AD, including psoriasis (22%), thyroiditis (20%), rheumatoid arthritis (13%), polymyalgia rheumatica (8%), inflammatory bowel disease (6%), multiple sclerosis (3%), and lupus (3%). Most received CPI as first- or second-line (77% of RCC patients; 93% of UC patients) and anti-PD/L1 monotherapy (65% of RCC patients; 98% of UC patients).
At start of CPI therapy, 36 patients had clinically active AD (all grade 1-2) and four required systemic immunosuppression. Thirty-eight patients had AD exacerbations, including arthritis (12% RCC; 24% UC), and rash (11% RCC; 9% UC).
Thirty-seven patients experienced new onset immune-related AEs, including colitis (12% RCC; 4% UC), rash (11% RCC; 9% UC), hypothyroid (7% RCC; 7% UC), and nephritis (7% UC).
Median follow-up was 12.5 months (range, 1-52 months) for RCC and 14.5 months (range, 1-53 months) for UC. Median time on CPI was 6 months (range, 1-36 months) for RCC and 4 months (range, 0.5-40 months) for UC. At time of data cutoff, 39 patients with RCC and 36 with US had discontinued CPI: 16% for toxicity. ORR was 31% for patients with RCC and 35% for patients with UC. The 1-year overall survival rate was 74% (95% confidence interval [CI], 58%-84%) for patients with RCC and 60% (95% CI, 43%-74%) for patients with UC.
“AD exacerbations or new acquired immune related AEs occurred in 37% and 36%, respectively, and were generally manageable. Only a minority required CPI cessation due to toxicity,” the researchers said.
Source: Chanza NM, Xie W, Issa M, et al. 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). Abstract of poster 4571 presented at the American Society of Clinical Oncology 2019 Annual Meeting, June 3, 2019, Chicago, Illinois.