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

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

doi:10.1016/j.jdin.2023.11.014

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

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

Authors

Xue Bai^{1

2}, Aleigha R Lawless², Juliane A Czapla², Stefanie C Gerstberger², Benjamin C Park³, Seungyeon Jung³, Rebecca Johnson⁴, Naoya Yamazaki⁵, Dai Ogata⁵, Yoshiyasu Umeda⁶, Caili Li¹, Jun Guo¹, Keith T Flaherty², Yasuhiro Nakamura⁶, Kenjiro Namikawa⁵, Georgina V Long⁴, Alexander M Menzies⁴, Douglas B Johnson³, Ryan J Sullivan², Genevieve M Boland⁷, Lu Si¹

Affiliations

¹ Department of Melanoma and Sarcoma, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Peking University Cancer Hospital and Institute, Beijing, China.
² Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts.
³ Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
⁴ Melanoma Institute Australia, The University of Sydney, Faculty of Medicine and Health, The University of Sydney, and Department of Medical Oncology, Royal North Shore and Mater Hospitals, Sydney, Australia.
⁵ Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan.
⁶ Department of Skin Oncology/Dermatology, Comprehensive Cancer Center, Saitama Medical University International Medical Center, Saitama, Japan.
⁷ Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Masssachusetts.

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.