Management of early melanoma recurrence despite adjuvant anti-PD-1 antibody therapy ☆ .

Background: Anti-programmed cell death protein 1 (PD-1) antibodies (PD1) prolong recurrence-free survival in high-risk resected melanoma; however, approximately 25%-30% of patients recur within 1 year. This study describes the pattern of recurrence, management and outcomes of patients who recur with adjuvant PD1 therapy.
Patients and Methods: Consecutive patients from 16 centres who recurred having received adjuvant PD1 therapy for resected stage III/IV melanoma were studied. Recurrence characteristics, management and outcomes were examined; patients with mucosal melanoma were analysed separately.
Results: Melanoma recurrence occurred in 147 (17%) of ∼850 patients treated with adjuvant PD1. In those with cutaneous melanoma (n = 136), median time to recurrence was 4.6 months (range 0.3-35.7); 104 (76%) recurred during (ON) adjuvant PD1 after a median 3.2 months and 32 (24%) following (OFF) treatment cessation after a median 12.5 months, including in 21 (15%) who ceased early for toxicity. Fifty-nine (43%) recurred with locoregional disease only and 77 (57%) with distant disease. Of those who recurred locally, 22/59 (37%) subsequently recurred distantly. Eighty-nine (65%) patients received systemic therapy after recurrence. Of those who recurred ON adjuvant PD1, none (0/6) responded to PD1 alone; 8/33 assessable patients (24%) responded to ipilimumab (alone or in combination with PD1) and 18/23 (78%) responded to BRAF/MEK inhibitors. Of those who recurred OFF adjuvant PD1, two out of five (40%) responded to PD1 monotherapy, two out of five (40%) responded to ipilimumab-based therapy and 9/10 (90%) responded to BRAF/MEK inhibitors.
Conclusions: Most patients who recur early despite adjuvant PD1 develop distant metastases. In those who recur ON adjuvant PD1, there is minimal activity of further PD1 monotherapy, but ipilimumab (alone or in combination with PD1) and BRAF/MEK inhibitors have clinical utility. Retreatment with PD1 may have activity in select patients who recur OFF PD1.
Competing Interests: Disclosure CNO reports non-financial support from Merck Sharp Dohme (MSD), outside the submitted work. ANS reports grants and personal fees from Bristol-Myers Squibb (BMS), during the conduct of the study; grants and personal fees from Immunocore, grants from Xcovery, grants, personal fees and non-financial support from Castle Biosciences, outside the submitted work. DC reports personal fees from BMS, personal fees from Novartis, outside the submitted work. JM reports other from Merck/Pfizer, other from MSD, other from Pierre Fabre, grants and other from Ultrasun, L'Oreal, Pierre Fabre, MSD, BMS, outside the submitted work. VA reports personal fees and non-financial support from BMS, personal fees from MSD, personal fees from Novartis, personal fees and non-financial support from Pierre Fabre, personal fees from Merck Serono, personal fees from Roche, non-financial support from Onco-sec, outside the submitted work. AY reports grants from National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number R38HL143619. CH reports personal fees from Amgen, personal fees from BMS, personal fees from Incyte, personal fees from MSD, personal fees from Novartis, personal fees from Pierre Fabre, personal fees from Roche, outside the submitted work. RD has intermittent, project focused consulting and/or advisory relationships with Novartis, MSD, BMS, Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome outside the submitted work. MM reports personal fees and non-financial support from MSD, personal fees and non-financial support from BMS, personal fees and non-financial support from AstraZeneca, personal fees and non-financial support from Roche, personal fees from Novartis, outside the submitted work. SPP reports personal fees from Merck & Co, Incyte, Castle Biosciences and Cardinal Health, and institutional clinical trial support from Provectus, Ideaya and BMS outside the submitted work. AH reports personal fees from BMS, personal fees from Pierre Fabre, personal fees from Merck, outside the submitted work. DBJ reports other from Array Biopharma, grants and other from BMS, grants and other from Incyte, other from Merck, other from Novartis, other from Genentech, outside the submitted work. CUB reports personal fees from BMS, MSD, GSK, Lilly, Roche, Novartis, Pfizer, GenMab, AZ, Pierre Fabre, grants from BMS, NanoString, Novartis, outside the submitted work; and stockownership Unitit Cars, Neon Therapeutics. SS reports grants and other from MSD, grants and other from BMS, grants from Amgen, grants from Endocyte, grants from Astra Zeneca, other from Roche, outside the submitted work. MSC reports personal fees from BMS, personal fees from MSD, personal fees from Novartis, personal fees from Roche, personal fees from Amgen, personal fees from Pierre Fabre, personal fees from Ideaya, outside the submitted work. JMGL reports grants and personal fees from Achilles therapeutics, personal fees from AstraZeneca, personal fees from Boston Biomedical, grants and personal fees from BMS, personal fees from Eisai, personal fees from EUSA Pharma, personal fees from GSK, personal fees from Ipsen, personal fees from Imugene, personal fees from Incyte, personal fees from iOnctura, personal fees from Kymab, personal fees from Merck Sorono, grants and personal fees from MSD, grants and personal fees from Nektar, grants and personal fees from Novartis, personal fees from Pierre Fabre, grants and personal fees from Pfizer, grants and personal fees from Roche/Genetech, personal fees from Secarna, personal fees from Vitaccess, personal fees from Covance, grants and personal fees from Immunocore, grants from Aveo, grants from Pharmacyclics, outside the submitted work. AMM reports personal fees from BMS, personal fees from MSD, personal fees from Novartis, personal fees from Roche, personal fees from Pierre Fabre, outside the submitted work. GVL is a Consultant Advisor and reports the following outside of the submitted work; personal fees from Aduro, personal fees from Amgen, personal fees from Array, personal fees from BMS, personal fees from MSD, personal fees from Novartis, personal fees from Pierre Fabre, personal fees from Oncosec, personal fees from Roche, personal fees from Sandoz. All other authors have declared no conflicts of interest.
(Copyright © 2020 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)