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. 2024 Jan 19:15:105-114.
doi: 10.1016/j.jdin.2023.11.014. eCollection 2024 Jun.

Benefit, recurrence pattern, and toxicity to adjuvant anti-PD-1 monotherapy varies by ethnicity and melanoma subtype: An international multicenter cohort study

Xue Bai  1   2 , Aleigha R Lawless  2 , Juliane A Czapla  2 , Stefanie C Gerstberger  2 , Benjamin C Park  3 , Seungyeon Jung  3 , Rebecca Johnson  4 , Naoya Yamazaki  5 , Dai Ogata  5 , Yoshiyasu Umeda  6 , Caili Li  1 , Jun Guo  1 , Keith T Flaherty  2 , Yasuhiro Nakamura  6 , Kenjiro Namikawa  5 , Georgina V Long  4 , Alexander M Menzies  4 , Douglas B Johnson  3 , Ryan J Sullivan  2 , Genevieve M Boland  7 , Lu Si  1
Affiliations

Benefit, recurrence pattern, and toxicity to adjuvant anti-PD-1 monotherapy varies by ethnicity and melanoma subtype: An international multicenter cohort study

Xue Bai et al. JAAD Int. .

Abstract

Background: Anti-Program-Death-1 (PD-1) is a standard adjuvant therapy for patients with resected melanoma. We hypothesized that there are discrepancies in survival, recurrence pattern and toxicity to adjuvant PD-1 between different ethnicities and melanoma subtypes.

Objective: We performed a multicenter cohort study incorporating 6 independent institutions in Australia, China, Japan, and the United States. The primary outcomes were recurrence free survival (RFS) and overall survival (OS). Secondary outcomes were disease recurrence patterns and toxicities.

Results: In total 534 patients were included. East-Asian/Hispanic/African reported significantly poorer RFS/OS. Nonacral cutaneous or melanoma of unknown primary reported the best RFS/OS, followed by acral, and mucosal was the poorest. Within the nonacral cutaneous or melanoma of unknown primary subtypes, East-Asian/Hispanic/African reported significantly poorer RFS/OS than Caucasian. In the multivariate analysis incorporating ethnicity/melanoma-subtype/age/sex/stage/lactate dehydrogenase/BRAF (v-Raf murine sarcoma viral oncogene homolog B)-mutation/adjuvant radiotherapy, East-Asian/Hispanic/African had independently significantly poorer outcomes (RFS: HR, 1.71; 95% CI, 1.19-2.44 and OS: HR, 2.34; 95% CI, 1.39-3.95), as was mucosal subtype (RFS: HR, 3.25; 95% CI, 2.04-5.17 and OS: HR, 3.20; 95% CI, 1.68-6.08). Mucosal melanoma was an independent risk factor for distant metastasis, especially liver metastasis. East-Asian/Hispanic/African had significantly lower incidence of gastrointestinal/musculoskeletal/respiratory/other-rare-type-toxicities; but higher incidences of liver toxicities.

Limitations: A retrospective study.

Conclusions: Ethnicity and melanoma subtype are associated with survival and recurrence pattern in melanoma patients treated with adjuvant anti-PD-1. Toxicity profile differs by ethnicity and may require a precision toxicity surveillance strategy.

Keywords: adjuvant PD-1; efficacy; ethnicity; melanoma subtype; toxicity.

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Conflict of interest statement

Dr Yamazaki has received honoraria from Ono pharmaceutical, 10.13039/100002491Bristol-Myers Squibb, MSD, 10.13039/100004336Novartis, and Maruho; has received research grant from Ono pharmaceutical, 10.13039/100002491Bristol-Myers Squibb, 10.13039/100004336Novartis, and 10.13039/100002429Amgen. Dr Ogata has received honoraria from MSD, Novartis, Ono pharmaceutical, and Bristol-Myers Squibb. Dr Nakamura serves on a scientific advisory board and educational steering committee for 10.13039/100004336Novartis, has received honoraria from BMS, Kyowa-Kirin, Maruho, MSD, 10.13039/100004336Novartis, Ono Pharma, and Tanabe-Mitsubishi Pharma, and received institutional grants from Kaken Pharma, Ono, Pola Pharma, and Torii. Dr Namikawa has received honoraria from Ono pharmaceutical, Novartis, Bristol-Myers Squibb, and MSD; serves as an advisory role for Novartis and MSD. Dr Guo serves as consultant or is on advisory boards for MSD, Roche, Pfizer, Bayer, Novartis, Simcere Pharmaceutical Group, Shanghai Junshi Biosciences, and Oriengene. Dr Flaherty serves on the Board of Directors of Clovis Oncology, Strata Oncology, Vivid Biosciences, and Scorpion Therapeutics;Scientific Advisory Boards of PIC Therapeutics, Apricity, Tvardi, ALX Oncology, xCures, Monopteros, Vibliome, and Soley Therapeutics; consultant to Takeda, Novartis and Transcode Therapeutics. Dr Long serves as a consultant advisor for Agenus, Amgen, Array Biopharma, AstraZeneca, Boehringer Ingelheim, BMS, Evaxion, Hexal AG (Sandoz Company), Highlight Therapeutics S.L., Innovent Biologics, MSD, Novartis, OncoSec, PHMR Ltd, Pierre-Fabre, Provectus, Qbiotics, Regeneron. Dr Menzies serves as a consultant for BMS, MSD, Novartis, Roche, Pierre-Fabre and QBiotics. Dr D.B. Johnson has served on advisory boards or as a consultant for BMS, Catalyst Biopharma, Iovance, Jansen, Mallinckrodt, Merck, Mosaic ImmunoEngineering, Novartis, Oncosec, Pfizer, Targovax, and Teiko, has received research funding from BMS and Incyte. Dr Sullivan serves as consultant for Amgen, Asana Biosciences, BMS, Merck, Novartis, Array BioPharma, Compugen, and Replimune; he receives research support from Amgen and Merck. Dr Boland has a sponsored research agreements with Takeda Oncology, Palleon Pharmaceuticals, InterVenn Biosciences, and Olink Proteomics; serves as a consultant for 10.13039/100004334Merck, InterVenn Biosciences, and Ankyra Therapeutics; served as a speaker for Novartis; and served on a scientific advisory board and steering committee for Nektar Therapeutics. Dr Si has received speakers’ honoraria from MSD, Roche, Novartis, Shanghai Junshi Biosciences and Oriengene. Drs Bai, Gerstberger, Park, Umeda and Authors Lawless, Czapla, Jung, R. Johnson, Li have no conflicts of interest to declare.

Figures

Fig 1
Fig 1
Flow chart.
Fig 2
Fig 2
RFS and OS across different ethnicities and melanoma subtypes. A, RFS across different ethnicities (n = 532). B, RFS across different melanoma subtypes (n = 534). C, OS across different ethnicities (n = 532). D, RFS across different melanoma subtypes (n = 534).
Fig 3
Fig 3
IrAE incidence by ethnicity (n =531, ∗with statistical significance).
See this image and copyright information in PMC

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