Early versus late response to PD-1-based immunotherapy in metastatic melanoma.

BACKGROUND

Immune checkpoint inhibition (ICI) currently is the most effective treatment to induce durable responses in metastatic melanoma. The aims of this study are the characterization of patients with early, late and non-response to ICI and analysis of survival outcomes in a real-world patient cohort.

METHODS

Patients who received PD-1-based immunotherapy for non-resectable stage-IV melanoma in any therapy line were selected from the prospective multicenter real-world DeCOG study ADOREG-TRIM (NCT05750511). Patients showing complete (CR) or partial (PR) response already during the first 3 months of treatment (Early Responders, EarlyR) were compared to patients showing CR/PR at a later time (Late Responders, LateR), a stable disease (SD) and to patients showing progressive disease (Non-Responders, NonR).

RESULTS

Of 522 patients, 8.2 % were EarlyR (n = 43), 19.0 % were LateR (n = 99), 37.0 % had a SD (n = 193) and 35.8 % were NonR (n = 187). EarlyR, LateR and SD patients had comparable baseline characteristics. Multivariate logbinomial regression analyses adjusted for age and sex revealed positive tumor PD-L1 (RR=1.99, 95 %-CI=1.14-3.46, p = 0.015), and normal serum CRP (RR=1.59, 95 %-CI=0.93-2.70, p = 0.036) as independently associated with the achievement of an early response compared to NonR. The median progression-free and overall survival was 46.0 months (95 % CI 19.1; NR) and 47.8 months (95 %-CI 36.9; NR) for EarlyR, NR (95 %-CI NR; NR) for LateR, 8.1 months (7.0; 10.4) and 35.4 months (29.2; NR) for SD, and 2.0 months (95 %-CI 1.9; 2.1) and 6.1 months (95 %-CI 4.6; 8.8) for NonR patients.

CONCLUSION

Less than 10 % of metastatic melanoma patients achieved an early response during the first 3 months of PD-1-based immunotherapy. Early responders were not superior to late responders in terms of response durability and survival.

Informations de copyright

Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest GCL received travel support from Sun Pharma, Pierre Fabre, research funding from Novartis. RH is employee of Helios Kliniken GmbH. PT has received honoraria from Bristol-Myers Squibb, Novartis, Merck Sharp & Dohme, Pierre Fabre, CureVac, Merck Serono, Sanofi, Roche, Kyowa Kirin and Biofrontera; and travel support from Bristol-Myers Squibb and Pierre Fabre. JU received honoraria (speaker honoraria or honoraria as a consultant) and travel support from Bristol-Myers Squibb, Kyowa Kirin, Merck Sharp & Dohme, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi/Regeneron, Sunpharma outside the submitted work. CP received honoraria (speaker honoraria or honoraria as a consultant) and travel support from Novartis, BMS, MSD, Merck Serono, MSD, Celgene, AbbVie, Sunpharma, Pierre Fabre, UCB, Nutricia Milupa, Janssen and LEO, outside the submitted work. JU is on the advisory board or has received honoraria and travel support from Amgen, Bristol Myers Squibb, GSK, Immunocore, LeoPharma, Merck Sharp and Dohme, Novartis, Pierre Fabre, Roche, Sanofi outside the submitted work. AK served as a speaker and/or consultant and/or advisory board for MSD, AbbVie, Boehringer Ingelheim, Janssen, and Sanofi. PM declares research support from Bristol Myers Squibb, Merck Sharp & Dohme and Novartis; speakers and advisory board honoraria from Bristol Myers Squibb, Beiersdorf, Merck Sharp & Dohme, Pierre Fabre, Sun Pharma, Immunocore, Sanofi and Novartis, and travel support from Bristol Myers Squibb, Merck Sharp & Dohme, Sanofi, Sun Pharma, and Pierre Fabre, outside the submitted work. RG received honoraria as speaker from BMS, MSD, Novartis, Amgen, Merck Serono, Almirall Hermal, SUN, Sanofi/Regeneron, Pierre-Fabre, as advisory board member from BMS, Novartis, Almirall Hermal, MSD, Amgen, SUN, Sanofi/Regeneron, Pierre-Fabre, 4SC, MerckSerono, Pfizer, Immunocore, Delcath, for meeting support from SUN, Pierre-Fabre, Boehringer Ingelheim and for research projects (to institution) from Amgen, Merck-Serono, SUN Pharma, Sanofi/Regeneron, Kyowa-Kirin, Almirall-Hermal. FM has received travel support or/and speaker’s fees or/and advisor’s honoraria by Novartis, Roche, BMS, MSD, Pierre Fabre, Sanofi and Immunocore and research funding from Novartis and Roche. MW received grants from Bristol-Myers Squibb and Merck Sharp & Dohme, consulting fees from Merck Sharp & Dohme, Immunocore and Novartis, lecture honoraria from Bristol-Myers Squibb and Merck Sharp & Dohme and Pierre-Fabre, and advisory board honoraria from Merck Sharp & Dohme. AP reports grants from Bristol Myers Squibb (BMS) and Merck Sharp & Dohme (MSD) outside the submitted work. JCB is receiving speaker’s bureau honoraria from Amgen, Pfizer, Recordati and Sanofi, and is a paid consultant/advisory board member/DSMB member for Almirall, Boehringer Ingelheim, InProTher, ICON, MerckSerono, Pfizer, 4SC, and Sanofi/Regeneron. His group received research grants from Bristol-Myers Squibb, Merck Serono, HTG, IQVIA, and Alcedis. EL served as consultant and/or has received honoraria from Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre-Fabre, Sanofi, Sunpharma, Takeda and travel support from Bristol-Myers Squibb, Pierre- Fabre, Sunpharma and Novartis, outside the submitted work. LZ served as consultant and has received honoraria from BMS, MSD, Novartis, Pierre Fabre, Sanofi, and Sunpharma and travel support from MSD, BMS, Pierre Fabre, Sanofi, Sunpharma and Novartis, outside the submitted work. DS reports partial financial support from Bristol Myers Squibb for the conduct of this study and drug supply (nivolumab and ipilimumab) support; grants (or contracts) from Amgen, Array/Pfizer, Bristol-Myers Squibb, MSD, Novartis and Roche; consulting fees from 4SC, Amgen, Array Biopharma, AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Haystick, Immunocore, InFlarX, Innocent, LabCorp, Merck Serono, MSD, Nektar, NeraCare, Novartis, OncoSec, Pfizer, Philogen, Pierre Fabre, Replimune, Roche, Sandoz, Sanofi/Regeneron, Sun Pharma; honoraria from Bristol-Myers Squibb, MSD/Merck, Merck Serono, Novartis, Roche, Sanofi and Sun Pharma; support for attendings meetings or travel support from Bristol-Myers Squibb, MSD, Merck Serono, Novartis, Pierre Fabre and Sanofi; participation on drug safety monitoring or advisory boards for 4SC, Amgen, Array Biopharma, AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Immunocore, InFlarX, Merck Serono, MSD, Nektar, NeraCare, Novartis, OncoSec, Pfizer, Philogen, Pierre Fabre, Replimune, Roche, Sandoz, Sanofi/Regeneron and SunPharma; leadership roles for DeCOG, German Cancer Society, Hiege-Stiftung, Deutsche Hautkrebsstiftung, NVKH e.V. and EuMelaReg. 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, and Novartis; and meeting and travel support from Almirall, Bristol-Myers Squibb, IGEA Clinical Biophysics, Merck Sharp & Dohme, Novartis, Pierre Fabre, and Sun Pharma. All other authors declared no conflict of interest.