Abstract 3945
Background
Immune checkpoint inhibitors (ICI) have demonstrated efficacy in many cancers. Patients can experience immune-related adverse events (irAE) and their management become crucial. Evidence-based guidance regarding the safety of rechallenge remains scarce. This study aims to prospectively investigate the safety of patients rechallenged after irAE.
Methods
Patients rechallenged after irAE grade ≥2 induced by anti-PD(L)1 and referred at the multidisciplinary board committee of immune toxicity (iTOX) of Gustave Roussy between August 2015 and December 2017 were included in this study.
Results
One hundred eighteen patients had a confirmed irAE. Median age was 62. Tumour types were melanoma (25.4%, n = 30), lung carcinoma (22.9%, n = 27), colorectal cancer (8.5%, n = 10), lymphoma (7.6%, n = 9), renal cell carcinoma (7.6%, n = 9), urothelial (6.8%, n = 8) and others (21.2%, n = 25). IrAE distribution was grade 2 (n = 56, 47.5%), grade 3 (n = 44, 37.3%) and grade 4 (n = 18, 15.2%). IrAE toxicities were hepatitis (15.2%, n = 18), skin toxicities (14.4%, n = 17), pneumonitis (13.6%, n = 16), colitis (10.2%, n = 12), arthralgia (8.4%, n = 10), hematologic (7.6%, n = 9) muscular (6.8%, n = 8), neurologic (5.9%, n = 7), ocular (5.1%, n = 6) toxicities, lipase increases (4.2%, n = 5), endocrine (4.2%, n = 5), nephrologic (2.5%, n = 3), cardiac toxicities (0.8%, n = 1) and infused related reaction (0.8%, n = 1). Forty patiens (33.8%) were hold and then rechallenged. Rechallenged and non-rechallenged patients didn't differ in term of age, distributions and grades of toxicity and steroids use. Patients were rechallenged after an irAE grade 2 (n = 18, 45%), grade 3 (n = 17, 42.5%) grade 4 (n = 5, 12.5%). 40% (16/40) had no recurrence, 35% (14/40) had recurrence of the same irAE, 15% (6/40) experienced a new irAE, and 10% (4/43) had multiple irAE. No patient had died after rechallenge. IrAE recurrence rates rates were 3/5 for colitis, 3/6 for arthralgia, 3/5 for hepatitis, 1/5 for pneumonitis, 0/3 for pancreatitis, 2/3 for neutropenia, 3/7 for skin toxicities. Recurrence rates were not different in grade 2 compared to grades 3-4.
Conclusions
The rechallenge of ICI after mild or severe irAE was associated with 60% of irAE grade ≥2 recurrence or new irAE. Toxicity profile was acceptable but required a close monitoring.
Clinical trial identification
Legal entity responsible for the study
Département des Innovations Thérapeutiques et Essais Précoces, Gustave Roussy, Université Paris-Saclay.
Funding
Has not received any funding.
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.
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