Safety and efficacy of restarting immune checkpoint inhibitors (CPI) after immune-related adverse events (irAEs) in metastatic renal cell carcinoma (mRCC).

Abstract

652 Background: CPI can induce a range of irAEs with various degrees of severity. Clinical experience with retreatment following clinically significant irAEs is growing. Methods: We retrospectively reviewed mRCC patients treated with CPI-based regimens who had >1 week therapy delay for irAEs at Dana Farber and Emory to characterize the safety and outcomes of retreatment. Toxicity was graded by CTCAEv5. Patients were divided into retreatment (R) and discontinuation (D) cohorts. Patient characteristics were compared by Fisher’s exact test or Wilcoxon’s rank sum test. ORR, OS and PFS were assessed descriptively. Results: Of 339 treated with CPI, 53 (16%) had irAEs warranting treatment interruption: 24 (45%) in R and 29 (55%) in D. Median (med) time to drug interruption was 2.0 (<0.1-74) months (mos) in D and 3.2 (<0.1-21) mos in R (p=0.89). Prior to irAE onset, 8 (28%) of cohort D and 5 (21%) of cohort R experienced partial responses (PR). While type of irAEs were balanced across D and R, initial irAEs were less severe in R vs D (all p<0.05) with fewer grade (gr) 3-4 events (29% vs 66%), less hospitalizations (25% vs 69%), and lower steroid requirements (>40 mg: 29% vs 79%). The most common irAEs in R were transaminitis, pancreatitis and dermatitis with 7 gr 3/4 events (pancreatitis, colitis, adrenal insufficiency and dermatitis). Median drug break before retreatment was 1.2 (0.3-4.8) mo. Subsequent irAEs occurred in 42% (n=10) after restarting (8 new, 2 recurrent) with 2 discontinuations; 6/10 were gr 3 with no gr 4/5 events. Median interval to irAE recurrence after retreatment was 2.1 (0.5-3.3) mos. Retreatment resulted in 4 (17%) PRs in patients whose disease had not responded prior to irAE (med time to PR from R = 2 mos). Conclusions: Despite a significant rate of irAE recurrence, most patients with prior clinically significant irAEs can be safely retreated. Retreatment can induce responses in an appreciable proportion of patients with no response prior to irAE. Larger studies are warranted to confirm these findings. [Table: see text]