Rechallenge of ipilimumab and nivolumab in advanced melanoma patients after previous ipilimumab-based therapy

Background: Ipilimumab+nivolumab (IPINIVO) can induce durable responses in advanced melanoma, but many patients experience progression at some point. It is currently unknown to what extent these patients benefit from IPINIVO rechallenge. This study describes efficacy and safety of IPINIVO rechallenge. Methods: Data from advanced melanoma patients rechallenged with IPINIVO after previous ipilimumab-containing treatment were retrieved from the nationwide Dutch Melanoma Treatment Registry. Patient characteristics, responses, survival, and safety were analyzed. Results: Among 3.759 patients receiving ipilimumab-containing treatment, 73 received rechallenge IPINIVO. 41 received IPINIVO, 32 ipilimumab monotherapy (IPI) as initial therapy. Objective response to rechallenge IPINIVO was seen in 36.1% (initial IPINIVO) and 40.0% (initial IPI) of patients. Median progression-free survival after rechallenge was 2.8 months (initial IPINIVO) and 5.6 months (initial IPI), but reached 18.4 months for responders to rechallenge therapy. Grade ≥3 immune-related adverse events occurred in 40.5% (initial IPINIVO) and 38.7% (initial IPI) of patients. Objective responses to initial and rechallenge treatment were discordant in 48.6% (initial IPINIVO) and 53.3% (initial IPI) of patients. Fifteen patients (20.5%) responded to rechallenge therapy but not to initial treatment. Conclusions: Rechallenge IPINIVO after previous ipilimumab-based therapy had a considerable response rate, acceptable safety profile, and potential for a durable response.