Single-agent anti-PD-1 or combined with ipilimumab in patients with mucosal melanoma: an international, retrospective, cohort study.

BACKGROUND

Mucosal melanoma (MM) is a rare melanoma subtype with distinct biology and poor prognosis. Data on the efficacy of immune checkpoint inhibitors (ICIs) are limited. We determined the efficacy of ICIs in MM, analyzed by primary site and ethnicity/race.

PATIENTS AND METHODS

A retrospective cohort study from 25 cancer centers in Australia, Europe, USA and Asia was carried out. Patients with histologically confirmed MM were treated with anti-programmed cell death protein 1 (PD-1) ± ipilimumab. Primary endpoints were response rate (RR), progression-free survival (PFS), overall survival (OS) by primary site (naso-oral, urogenital, anorectal, other), ethnicity/race (Caucasian, Asian, Other) and treatment. Univariate and multivariate Cox proportional hazards model analyses were conducted.

RESULTS

In total, 545 patients were included: 331 (63%) Caucasian, 176 (33%) Asian and 20 (4%) Other. Primary sites included 113 (21%) anorectal, 178 (32%) urogenital, 206 (38%) naso-oral and 45 (8%) other. Three hundred and forty-eight (64%) patients received anti-PD-1 and 197 (36%) anti-PD-1/ipilimumab. RR, PFS and OS did not differ by primary site, ethnicity/race or treatment. RR for naso-oral was numerically higher for anti-PD-1/ipilimumab [40%, 95% confidence interval (CI) 29% to 54%] compared with anti-PD-1 (29%, 95% CI 21% to 37%). Thirty-five percent of patients who initially responded progressed. The median duration of response (mDoR) was 26 months (95% CI 18 months-not reached). Factors associated with short PFS were Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥3 (P < 0.01), lactate dehydrogenase (LDH) more than the upper limit of normal (ULN) (P = 0.01), lung metastases (P < 0.01) and ≥1 previous treatments (P < 0.01). Factors associated with short OS were ECOG PS ≥1 (P < 0.01), LDH >ULN (P = 0.03), lung metastases (P < 0.01) and ≥1 previous treatments (P < 0.01).

CONCLUSIONS

MM has poor prognosis. Treatment efficacy of anti-PD-1 ± ipilimumab was similar and did not differ by ethnicity/race. Naso-oral primaries had numerically higher response to anti-PD-1/ipilimumab, without difference in survival. The addition of ipilimumab did not show greater benefit over anti-PD-1 for other primary sites. In responders, mDoR was short and acquired resistance was common. Other factors, including site and number of metastases, were associated with survival.

Informations de copyright

Copyright © 2022 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Disclosure FD: receives/received honoraria and travel support from Merck Sharp & Dohme Bristol-Myers Squibb and Sun Pharma. KN: honoraria from Ono Pharmaceutical, Novartis Pharma, Bristol-Myers Squibb and MSD. EIB: has received consulting fees from BMS and Novartis; has research funding paid to the institution from BMS, Merck, Novartis and Genentech. JAS: conference support from MSD. AZ: received travel support from Novartis, Sanofi Grenzyme and Bristol-Myers Squibb, outside the submitted work. MJM: served as a consultant for AstraZeneca, immunai, nektar therapeutics, catalyst pharmaceuticals and istari oncology. YN: consultant/advisory board—MSD, Novartis. Institutional research funding—Kaken, Ono pharma, Pola Pharma, Torii. Honoraria—BMS, Maruho, MSD, Novartis, Ono Pharma, Taisho Toyama, Taiho Pharma. XB: merit award supported by BMS.CA: Travel accommodations—meetings: Roche, BMS, AMGEN. AI: advisory board: Novartis. Honoraria for lectures: BMS, MSD, Novartis, Sanofi, Pierre-Fabre. MF: advisory board—Bayer. KCK: has served as consultant and/or has received honoraria from Amgen, Roche, Bristol Myers Squibb, Merck Sharp and Dohme, Pierre Fabre and Novartis, and received travel support from Amgen, Merck Sharp and Dohme, Bristol Myers Squibb, Amgen, Pierre Fabre, Medac and Novartis. VA: personal fees: Bristol Myers Squibb, Merck Serono, MSD, Novartis, Pierre Fabre, Roche, Oncosec. OK: personal fees from Bristol Myers Squibb and Merck Sharp & Dohme, outside the submitted work. AH: has served on advisory boards for BMS, MSD, Novartis, Pierre Fabre and Q Biotic. RDC: consultant/advisory board—Alkermes, Aura Biosciences, Bristol Myers Squibb, Castle Biosciences, Chimeron, Ideaya, Immunocore, InxMed, Iovance, Merck, Novartis, Oncosec, Pierre Fabre, PureTech Health, Regeneron, Rgenix, Sanofi Genzyme, Sorrento Therapeutics, Trisalus. OH: speaker’s bureau honoraria from BMS, Novartis, Pfizer and Sanofi Regeneron, and is an advisory board member/consultant for Aduro, Akeso Bio, Amgen, Beigene, Bioatla, BMS, Roche Genentech, GSK, Immunocore, Incyte, Janssen, Merck, Nextcure, Novartis, Pfizer, Sanofi Regeneron, Seagen, Tempus and Zelluna. AH: received grants and personal fees from Amgen, BMS, Immunocore, Novartis, MerckSerono, MSD/Merck, Philogen, Pierre Fabre, Regeneron, Replimune, Roche, Sanofi-Genzyme and Sun Pharma, outside the submitted work. MSC: consultant advisor for Amgen, BMS, Eisai, Ideaya, MSD, Nektar, Novartis, Oncosec, Pierre-Fabre, Qbiotics, Regeneron, Roche, Merck and Sanofi, and received honoraria from BMS, MSD and Novartis. MM: received honoraria for participation at advisory boards from Novartis, BMS, MSD, Pierre Fabre, Sanofi, reports lecture from Novartis, BMS, MSD, Pierre Fabre, Sanofi and reports grants from Roche, Novartis. CR: advisor for Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Sanofi, Merck, Roche, AstraZeneca and is scientific founder of Aglaia therapeutics. CL: BMS: research grant, honoraria, consultancy, speaker’s bureau, travel accommodations—meetings, advisory role, serving on an advisory board; MSD: honoraria, consultancy, advisory role, serving on an advisory board, travel accommodations—meetings; Novartis: honoraria, consultancy, speaker’s bureau, advisory role, serving on an advisory board; Amgen: honoraria, consultancy, speaker’s bureau, serving on an advisory board; Roche: research grant, honoraria, consultancy, speaker’s bureau, advisory role, serving on an advisory board; Avantis Medical Systems: board; Pierre-Fabre/Pfizer/Incyte: honoraria. JG: consultant/advisory boards for MSD, Roche, Pfizer, Bayer, Novartis, Simcere Pharmaceutical Group, Shanghai Junshi Biosciences and Oriengene. DBJ: advisory boards for Array Biopharma, Bristol Myers Squibb, Catalyst Biopharma, Iovance Biotherapeutics, Janssen, Merck, Novartis and OncoSec. Research support from Bristol Myers Squibb and Incyte. PAA: has/had a consultant/advisory role for Bristol Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, Merck Serono, Pierre-Fabre, AstraZeneca, Sun Pharma, Sanofi, Idera, Sandoz, Immunocore, 4SC, Italfarmaco, Nektar, Boehringer-Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore, Seagen, iTeos. He also received research funding from Bristol Myers Squibb, Roche-Genentech, Pfizer, Sanofi. ANS: advisory board/personal fees: Bristol-Myers Squibb, Immunocore, Novartis, Castle Biosciences. Institutional trial support: Bristol-Myers Squibb, Immunocore, Novartis, Xcovery, Polaris, Pfizer, Checkmate Pharmaceuticals, Forghorn Therapeutics. RJS: advisory board—BMS, Merck, Novartis, Pfizer; research support from Merck. LZ: served as consultant and/or has received honoraria from Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Sanofi, Sunpharma and travel support from Amgen, Merck Sharp & Dohme, Bristol-Myers Squibb, Pierre Fabre, Sanofi, Sunpharma and Novartis. SS: grants from Novartis, AstraZeneca, Merck Sharp & Dohme and Genentech; and personal fees from AstraZeneca, Merck Sharp & Dohme and Bristol Myers Squibb, outside the submitted work. CUB: personal fees from BMS, MSD, Roche, Novartis, GSK, AZ, Pfizer, Lilly, GenMab, Pierre Fabre, Third Rock Ventures, grants from BMS, Novartis, NanoString, other from Uniti Cars, Forty Seven, Neon Therapeutics, Verastem, other from Immagene B.V. RD: intermittent, project-focused consulting and/or advisory relationships with Novartis, Merck Sharp & Dohme (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. BCS: speaker’s bureau honoraria and personal fees from BMS, Novartis, MDS, Pierre Fabre. AMM: advisory board—BMS, MSD, Novartis, Roche, Pierre-Fabre, QBiotics. GVL: consultant advisor for Aduro Biotech Inc, Amgen Inc, Array Biopharma inc, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Highlight Therapeutics S.L., Merck Sharpe & Dohme, Novartis Pharma AG, Pierre Fabre, QBiotics Group Limited, Regeneron Pharmaceuticals Inc. All other authors have declared no conflicts of interest. Data sharing Availability of data and material: patients’ medical records. All data were anonymized immediately after collection.