Clinical outcomes of retreatment or discontinuation after interruption of nivolumab plus ipilimumab due to immune-related adverse events in metastatic renal cell carcinoma patients: A retrospective multicenter study.

[INTRODUCTION] We aimed to investigate clinical outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab plus ipilimumab (Nivo/Ipi) who either resumed or permanently discontinued treatment following immune-related adverse events (irAEs) that necessitated treatment interruption.

[PATIENTS AND METHODS] A database of 129 metastatic renal cell carcinoma (mRCC) patients treated with Nivo/Ipi at 6 Japanese institutions was analyzed, dividing the patients into 3 groups: those without treatment interruption ("no interruption"), those who resumed treatment after irAEs ("retreatment"), and those who permanently discontinued treatment after irAEs ("discontinuation").

[RESULTS] The no interruption, retreatment, and discontinuation group included 58, 35, and 36 patients, respectively. Median time to initial irAE requiring treatment interruption was comparable between the retreatment and discontinuation groups (2.1 vs. 2.6 months, P = 0.53). Although the type and severity of initial irAEs leading to interruption were evenly distributed between the retreatment and discontinuation groups, high-dose glucocorticoids were required less frequently in the retreatment group (7 vs. 16 patients, P = 0.033). Among the 35 patients in the retreatment group, 5 developed new irAEs and 2 experienced recurrences of previous irAEs, with grade 3/4 irAEs occurring in 3 patients. Objective response rates to Nivo/Ipi were 30%, 63%, and 64% in the no interruption, retreatment, and discontinuation groups, respectively. Progression-free survival (PFS) and overall survival (OS) were comparable between the retreatment and discontinuation groups (median PFS: 28.5 vs. 26.0 months, P = 0.60; 3-year OS: 69% vs. 78%, P = 0.70), whereas both were significantly shorter in the no interruption group (median PFS: 4.1 months; 3-year OS: 28%).

[CONCLUSION] Although resuming Nivo after irAEs requiring treatment interruption appears to be safe in carefully selected patients, permanent discontinuation also offers favorable oncological outcomes, indicating it may be a viable alternative.