Clinical benefit and toxicity of nivolumab plus ipilimumab in patients with advanced melanoma previously treated with checkpoint blockade inhibitors.

Abstract

100 Background: The combination of nivolumab and ipilimumab (nivo+ipi) prolongs progression-free survival in treatment-naïve patients (pts) with advanced melanoma. However, the efficacy and tolerability of nivo+ipi in pts previously treated with checkpoint blockade inhibitors (CPI) are unknown. Methods: 19 pts previously treated with CPI (ipi or anti-PD-1 as single agents) were treated with nivo+ipi at MSKCC. Ipi (3mg/kg) and nivo (1mg/kg) were administered q3 weeks for 4 doses with the option to continue anti-PD1 maintenance. Pts were followed for time to treatment failure (TTF), defined as the time from the date of first nivo+ipi infusion to the date of one of the following: clinical progression, new locally-directed treatment (ie surgery or radiotherapy), new systemic treatment other than anti-PD-1 monotherapy, or death. Results: 15 pts (79%) had stage M1c disease and 12 (63%) had a cutaneous primary. Pts had received a median of 2 prior systemic treatments (range 1-7). 10 pts (53%) had received prior ipi and 17 pts (89%) had received prior anti-PD-1 treatment; 8 pts (42%) had received both. The median time between anti-PD-1 monotherapy and nivo+ipi was 51 days (range 20-385). Pts received a median of 3 doses of combination therapy; 9 of 19 pts (47%) received all 4 doses. With a median follow-up time of 210 days, 8 pts (42.1%) remained on combination immune therapy, 9 pts (47%) switched systemic treatments or had a local procedure and 6 pts (31.6%) died. Median time on immunotherapy for those still alive and without treatment failure was 105 days (range 26-343). The median TTF was 78 days (range 42-220). The most common systemic treatment after nivo+ipi failure was BRAF-targeted therapy (5/9 or 56.3%). The median number of immune related adverse events (irAEs) was 1 (range 0-3). Rash (26%), Hepatitis (16%) and Colitis (16%) were the most common irAEs. Conclusions: With a short median follow-up, administration of nivo+ipi in CPI-experienced patients with advanced melanoma was associated with a short TTF. 58% of patients died or had treatment failure within the follow-up period. More research is needed to guide the utilization of combination immunotherapy in this setting.