Efficacy and safety of immune checkpoint inhibitors in young adults with metastatic melanoma.

Background: The integration of immune checkpoint inhibitors (ICI) for the treatment of melanoma has resulted in remarkable and durable responses. Given the potential role of immunosenescence, age may contribute to differential ICI efficacy and toxicity. While older patients have been studied in detail, outcomes from ICI in young patients (≤40 years) are not well characterised.
Methods: We performed a multi-institutional, retrospective study of patients with advanced melanoma treated with anti-PD-1 monotherapy or ICI combination (ipilimumab and anti-PD-1). Response rates, survival, and toxicities were examined based on age comparing those under 40 years of age with older patients (age 41-70 and ≥ 71 years).
Results: A total of 676 patients were included: 190 patients (28%) aged ≤40 years, 313 (46%) between ages 41-70, and 173 patients (26%) aged ≥71. Patients ≤40 years had higher response rates (53% vs 38%, p = 0.035) and improved progression-free survival (median 13.7 vs 4.0 months, p = 0.032) with combination ICI compared to monotherapy. Progression-free survival was similar among groups while overall survival was inferior in patients >70 years, who had low response rates to combination therapy (28%). ICIs had a similar incidence of severe toxicities, though hepatotoxicity was particularly common in younger patients vs. patients >40 with monotherapy (9% vs. 2%, p = 0.007) or combination ICI (37% vs. 10%, p < 0.001).
Conclusions: ICIs had comparable efficacy between younger and older patients, although outcomes were superior with combination ICI compared to monotherapy in patients aged ≤40 years. Toxicity incidence was similar across age groups, though organs affected were substantially different.
Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: DBJ has served on advisory boards or as a consultant for BMS, Catalyst Biopharma, Iovance, Jansen, Mallinckrodt, Merck, Mosaic ImmunoEngineering, Novartis, Oncosec, Pfizer, and Targovax, and has received research funding from BMS and Incyte. RJS has served on advisory boards or as a consultant for BMS, Eisai, Iovance, Merck, Novartis, Oncosec, and Pfizer, and has received research funding from Merck. GVL is a consultant advisor for Agenus, Amgen, Array Biopharma, Boehringer Ingelheim International, Bristol Myers Squibb, Evaxion, Hexal AG, Highlight Therapeutics, Merck Sharpe & Dohme, Novartis, OncoSec, Pierre Fabre, Provectus, Qbiotics, and Regeneron. MSC is a consultant advisor for Amgen, Bristol-Myers Squibb, Eisai, Ideaya, Merck Sharp and Dohme, Nektar, Novartis, Oncosec, Pierre-Fabre, Qbiotics, Regeneron, and Roche; honoraria: Bristol-Myers Squibb, Merck Sharp and Dohme, Novartis. AMM has served on advisory boards for BMS, MSD, Novartis, Roche, Pierre-Fabre, and QBiotics. IMR has served on advisory boards or as a consultant for Amgen, BMS, GSK, Novartis, MSD, Roche, Celegene, Pierre Fabre, Highlight Therapeutics (formerly Bioncotech), Regeneron, Sanofi, Merck Serono, Astra Zeneca, BiolineRx, and Sun Pharma. EMC has served on advisory boards or as a consultant for Amgen, BMS, GSK, Novartis, MSD, Roche, Celegene, Pierre Fabre, Regeneron, Sanofi, Merck Serono, Astra Zeneca, and Sun Pharma. LZ (MGH) has served on advisory boards or as a consultant for Merck. SU declares research support from Bristol Myers Squibb, and Merck Serono; speakers and advisory board honoraria from Bristol Myers Squibb, Merck Sharp & Dohme, Merck Serono, Novartis, and Roche, and travel support from Bristol Myers Squibb, Merck Sharp & Dohme, and Pierre Fabre; outside the submitted work. LZ (Essen) reports personal fees and other (advisory board participation, travel grants) from Bristol-Meyers-Squibb, MSD, Pierre Fabre, Roche, and Novartis; other (advisory board participation and/or travel grants) from Sanofi and Amgen; all outside the submitted work. EL reports personal fees and other (advisory board participation and/or travel grants) from Amgen, BMS, MSD, Novartis, Roche, and medac; personal fees from Janssen; other fees from Actelion and Pierre-Fabre; all outside the submitted work. DS reports research finding to the institution for clinical studies or research from BMS, MSD, Novartis, Amgen, Array; patient fees to the institution from BMS, MSD, Novartis, Merck-EMD, Philogen, Pfizer, Array, InflarX, OncoSec, Replimune, Neracare, Nektar, SunPharma, Sandoz, and UltimoVacs; reimbursement for travel from BMS, Merck, Novartis, Merck-EMD, Pfizer, Pierre Fabre, InflarX, NeraCare, and Nektar; non-financial support from BMS, MSD, Novartis, Merck-EMD, Pierre-Fabre, InFlarX, Neracare, Nektar, SunPharma, and Sandoz; all outside the submitted work. SMB has served as a consultant for Two River Consulting and Third Rock Ventures and reports equity holdings in Kronos Bio and 76Bio. All remaining authors declare no conflicts of interest.
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