Efficacy of anti-PD-1 rechallenge in metastatic melanoma: A retrospective analysis.

Abstract

e21544 Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of metastatic melanoma, but a subset of patients experiences disease progression after initial response. The concept of immunotherapy rechallenge—reintroducing ICIs in patients who previously responded and later relapsed—has gained attention as a potential therapeutic strategy, though its safety and efficacy remain unclear. Methods: We conducted from 2019 to 2023 a monocentric retrospective analysis of melanoma patients who underwent anti-PD-1 rechallenge following disease progression after initial treatment. Patients included in the study had either an initial response to immunotherapy (nivolumab, pembrolizumab, or nivolumab plus ipilimumab) followed by disease progression, and were rechallenged with anti-PD-1. All pts signed informed consent. Survival rates were analyzed using the Kaplan-Meier method. Hazard Ratios (HR) and their 95% confidence intervals (CI) were estimated using a Cox regression model. Results: A total of 84 patients were included in the analysis. The median total PFS following rechallenge was 19.4 months , with a median OS of 34,4 months. Forty-two pts (50%) performed combination nivolumab and ipilimumab as first line, of which 38% were treated with B-RAF/MEK inhibitors at first disease progression as mutated and then rechallenged with anti-PD-1 after a median time of 12,2 months from the last immunotherapy. The remain 12% were enrolled in clinical trial with other combinations and received rechallenge with anti-PD-1 after a median time of 6 months. The other forty-two pts (50%) were treated with anti-PD-1 monotherapy as first line and rechallenged with anti-PD-1 with a median time of 9,7 months. Overall response rate was 21% in both groups. Rechallenge in pts treated with the sequence anti-PD-1 alone/ ipi or target/anti-PD-1 showed better OS (42,1 vs 23,8 months , HR0,29 CI 0,10-0,84, p = 0,02) and PFS ( 27,6 vs 6,7 months, HR 0.35 (CI 0.27-0.89), p = 0.01. The safety profile was consistent with prior immunotherapy experiences. Conclusions: Rechallenge with anti-PD-1 in metastatic melanoma patients who have experienced progression after initial benefit appears to offer clinical benefit for some patients, with manageable safety risks. Further prospective studies are needed to define optimal rechallenge strategies and identify biomarkers predictive of response.