The concepts of rechallenge and retreatment with immune checkpoint blockade in melanoma patients
- PMID: 34392069
- DOI: 10.1016/j.ejca.2021.07.002
The concepts of rechallenge and retreatment with immune checkpoint blockade in melanoma patients
Abstract
Forty to 60% of patients with advanced or metastatic melanoma respond to first-line immune checkpoint inhibitors (ICI) and half of all patients in the metastatic setting eventually progress. This review evaluated the latest long-term data from clinical trials. It also considered data from recent retrospective studies, as these address important questions for clinical practice. 'Retreatment' defined as 'repeated treatment with the same therapeutic class following relapse after adjuvant treatment has ended' and showed activity in selected patients with recurrence after regular completion of adjuvant PD-1 treatment. In melanoma patients with adjuvant PD-1 monotherapy who recur during adjuvant treatment, further treatment with PD-1 monotherapy seems to have no clinical utility, indicating the need for a therapy switch or escalation in these patients. Targeted therapy with BRAF/MEK inhibitors and ipilimumab-based therapy (alone or combined with PD-1 blockade) show clinical activity in patients who recur during and after adjuvant treatment. 'Rechallenge', defined as 'repeated treatment with the same therapeutic class following disease progression in patients who had clinical benefit with prior treatment for unresectable or metastatic disease', with pembrolizumab at progression in the advanced setting achieving additional disease control. If possible, 'escalation' (PD-1 inhibitors combined with additional agents) should be preferred to PD-1 inhibitor monotherapy rechallenge as higher response rates were demonstrated. The combination of PD-1 plus CTLA-4 was found to be more effective but not more toxic than CTLA-4 alone. Promising antitumor activity was observed for escalation to lenvatinib plus pembrolizumab, entinostat plus pembrolizumab, and relatlimab plus nivolumab. Retreatment, rechallenge and escalation are available options for patients with melanoma who relapse in the adjuvant or advanced setting.
Keywords: Escalation; Immunotherapy; Melanoma; Rechallenge; Retreatment.
Copyright © 2021 Elsevier Ltd. All rights reserved.
Conflict of interest statement
Conflict of interest statement AZ reports receiving travel support from Novartis, Sanofi Genzyme, and Bristol-Myers Squibb, outside the submitted work. AMME reports a consultant or advisor role for Ellipses Pharma, GlaxoSmithKline, ISA Pharmaceuticals, MSD, Novartis, Pfizer, Sellas Life Sciences, Skyline Diagnostics, BioInvent, IO Biotech, CatalYm and Nektar, serving on the speaker's bureau for MSD and BIOCAD, receiving travel funding from Bristol Myers Squibb and received honoraria from Ellipses Pharma, GlaxoSmithKline, ISA Pharmaceuticals, MSD, Novartis, Pfizer, Sellas Life Sciences, Skyline Diagnostics, BIOCAD, CatalYm, BioInvent, IO Biotech, and Nektar, providing expert testimony for Novartis and having stock and other ownership interest with RiverD, Skyline Diagnostics, and Theranovir, all outside the submitted work. CR reports participation in advisory boards for Roche; Pierre Fabre; Merck; Novartis; Amgen; Bristol-MyersSquibb; Novartis; Merck Sharp & Dohme Corp., asubsidiary of Merck & Co., Inc., Kenilworth, NJ, U.S.A. (MSD); and Sanofi. RD reports having intermittent, project focused consulting and/or advisory relationships with Novartis, Merck Sharp & Dhome (MSD), Bristol-Myers Squibb (BMS), Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, Alligator, T3 Pharma, MaxiVAX SA and touchIME outside the submitted work. 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 and Merck Sharp & Dohme. EL reports serving as a consultant and/or receiving honoraria from Amgen, Actelion, Roche, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Janssen, Medac, Sanofi, Sunpharma and travel support from Amgen, Merck Sharp & Dohme, Bristol-Myers Squibb, Amgen, Pierre Fabre, Sunpharma and Novartis, outside the submitted work. PAA reports a consultant/advisory role for Bristol Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, Array, Merck Serono, Pierre-Fabre, Incyte, Medimmune, AstraZeneca, Syndax, Sun Pharma, Sanofi, Idera, Ultimovacs, Sandoz, Immunocore, 4SC, Alkermes, Italfarmaco, Nektar, Boehringer-Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore, Seagen, and iTeos. He also reports receiving research funding from Bristol Myers Squibb, Roche-Genentech, Array, and Sanofi and travel support from MSD. GVL reports being a consultant advisor for Aduro Biotech Inc, Amgen Inc, Array Biopharma Inc., Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Hexel AG, Highlight Therapeutics S.L., Merck Sharpe & Dohme, Novartis Pharma AG, OncoSec, Pierre Fabre, QBiotics Group Limited, Regeneron Pharmaceuticals Inc, SkylineDX B.V., and Specialised Therapeutics Australia Pty Ltd. DS reports personal fees and non-financial support from Roche/Genentech, grants, personal fees, non-financial support and other from BMS, personal fees from Merck Sharp & Dohme, personal fees and non-financial support from Merck Serono, grant, personal fees and non-financial support from Amgen, personal fees from Immunocore, personal fees from Incyte, personal fees from 4SC, personal fees from Pierre Fabre, personal fees and non-financial support from Sanofi/Regeneron, personal fees from Array BioPharma, personal fees from Pfizer, personal fees from Philogen, personal fees from Regeneron, personal fees from Nektar, personal fees from Sandoz, grants, personal fees and non-financial support from Novartis, and personal fees and non-financial support from SunPharma, Replimune, Helsinn, OncoSec and InFlaRx outside the submitted work. LZ reports being a consultant and/or receiving honoraria from Roche, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre-Fabre, Sunpharma and Sanofi; research funding to institution from Novartis; and travel support from Merck Sharp & Dohme, Bristol-Myers Squibb, Amgen, Pierre-Fabre, Sanofi, Sunpharma and Novartis, outside the submitted work.
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