Aims: Cumulative data indicate greater tumor response from the combination of NIVO+IPI in patients with MEL, but with higher frequency of adverse events (AEs) compared with either agent alone. This pooled analysis of 3 studies describes the safety profile of NIVO+IPI utilizing established guidelines for AE management.
Methods: A retrospective safety review was conducted for phase 1–3 trials in which patients received ≥1 dose of the standard regimen, NIVO 1 mg/kg + IPI 3 mg/kg Q3W x 4, then NIVO 3 mg/kg Q2W until progression or unacceptable toxicity. Analyses included AEs, select (immune-related) AEs, time to onset and resolution, use of immune-modulating agents (IMs) for toxicity management, and effect of IMs on outcome.
Results: Among 448 patients, median age was 61 years, and 25% had ECOG PS >0. Median duration of follow-up was 13.2 months. Treatment-related grade 3/4 AEs occurred in 55% of patients and led to discontinuation in 28%. The most frequent treatment-related select AEs of any grade were skin (64%) and gastrointestinal (47%), and of grade 3/4 were hepatic (17%) and gastrointestinal (16%); 30% developed a grade 2–4 select AE in >1 organ category. Median time to onset of grade 3/4 select AEs ranged from 3.1 (skin) to 16.3 weeks (renal). Excluding endocrine AEs, median time to resolution and resolution rates of grade 3/4 select AEs were 1.1 (renal) to 7.3 weeks (pulmonary) and 79–100%, respectively, using IMs. Four (<1%) deaths were attributed to therapy.
Conclusions: The frequency of grade 3/4 treatment-related AEs was higher with NIVO+IPI, and time to onset of select AEs occurred earlier than with either agent alone. Resolution rates of select AEs were similar to those previously reported with IPI monotherapy.