Long-term melanoma survival is now attainable with anti-PD-1 regimens. Notably, a subset of patients experience disease progression (PD) during their immunotherapy treatment but still survive >5 years. Factors that contribute to this prolonged survival despite initial PD are of great interest for prognostication and treatment selection.
We conducted a retrospective study of patients who survived >5 years from initial treatment with anti-PD-1 with advanced non-uveal melanoma at two centers. Overall survival (OS) was calculated from 5-years post initial anti-PD-1 treatment. Time to second progression was calculated from the date of initial progression on anti-PD-1 to date of second progression.
Of the 298 patients treated with anti-PD-1 who survived at least 5 years, 102 experienced disease progression. Median patient age was 62 years (range 22-90); 30 had unresectable stage III, 64 M1a, 75 M1b, 98 M1c, and 31 M1d disease. Patients received anti-PD(L)1 monotherapy (176) or nivolumab + ipilimumab (122). The best overall response to initial anti-PD-1 was complete response (150), partial response (92), stable disease (30), or PD (26). Median follow-up among survivors (274) was 79 months (range 60-143). OS at year 6 (1-year post 5-year landmark) was 94.9% (95% CI: 91.4-97.0%). 24 patients died after 5 years post initial anti-PD-1, 10 due to melanoma. In those who survived to 5 years without treatment failure, the probability of remaining treatment failure-free for an additional 2 years was 96.5% (95% CI: 93.4-99.6%). Among the 102 patients that progressed on initial anti-PD-1, 56 progressed at existing sites, 28 at new sites, and 18 at both. 6 patients experienced initial PD after 5 yrs. Probability of remaining free from progression at 5 and 10 years from initial anti-PD-1 was 67.8% (95% CI: 62.2-72.8%) and 64.4% (95% CI: 58.2-69.8%), respectively. 69 patients had a second progression; median time to second progression from initial progression was 36 (95% CI: 21-58) mos.
Patients who progress on initial anti-PD-1-based regimens but survive 5+ years have promising overall survival and low rates of second progression. These data help guide survivorship planning in patients who progress on anti-PD-1 and go on to respond to later lines of therapy.
The authors.
Has not received any funding.
K. Panageas: Financial Interests, Personal, Stocks/Shares: AstraZeneca, Catalyst Biotech, Dynavax Technologies, Pfizer, Sunesis Pharmaceuticals, Viking Therapeutics. D. Johnson: Financial Interests, Personal, Advisory Board: BMS, Catalyst, Iovance, Oncosec, Merck, Mallinckrodt, Pfizer, Novartis, Mosaic, Targovax; Financial Interests, Institutional, Funding: BMS; Financial Interests, Institutional, Invited Speaker: Incyte; Non-Financial Interests, Personal, Other, Guidelines: SITC; Non-Financial Interests, Personal, Other, Guidelines: NCCN. A. Betof Warner: Financial Interests, Personal, Advisory Role: Iovance Biotherapeutics, Novartis, Shanghai Jo'Ann Medical Technology, BluePath Solutions, Pfizer, Instil Bio, Lyell Immunopharma, Bristol-Myers Squibb/Medarex. All other authors have declared no conflicts of interest.