ONCOmmunity

Benefit and Toxicity to PD-1 Blockade Varies by Ethnicity in Patients with Advanced Melanoma: An International Multicenter Observational Study.

By: Xue Bai, Alexander N Shoushtari, Allison Betof Warner, Lu Si, Bixia Tang, Chuanliang Cui, Xiaoling Yang, Xiaoting Wei, Henry T Quach, Christopher G Cann, Michael Z Zhang, Lalit Pallan, Catriona Harvey, Michelle S Kim, Gyulnara Kasumova, Tatyana Sharova, Justine V Cohen, Donald P Lawrence, Christine Freedman, Riley M Fadden, Krista M Rubin, Dennie T Frederick, Keith T Flaherty, Georgina V Long, Alexander M Menzies, Ryan J Sullivan, Genevieve M Boland, Douglas B Johnson, Jun Guo

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Institute, Beijing, CHN.
2022-02-20; doi: 10.1111/bjd.21241

Abstract

Background

Programmed cell death receptor-1 (PD-1) monotherapy is a standard treatment for advanced cutaneous melanoma, but its efficacy and toxicity are defined in Caucasians and remain poorly characterized in other ethnic groups, such as East-Asians/Hispanics/Africans.

Methods

Clinical data for patients with unresectable or advanced melanoma treated with anti-PD-1 monotherapy between 2009 and 2019 was collected retrospectively from five independent institutions in the US, Australia and China. Tumor response, survival, and immune-related adverse events (irAEs) were compared by ethnicity (Caucasian versus East-Asian/Hispanic/African) across different melanoma subtypes (non-acral-cutaneous[NAC]/unknown primary[UP] and acral/mucosal/uveal).

Results

In total 1,135 patients were included. Caucasians had significantly higher ORR (54% [95% CI 50-57%] versus 20% [95% CI 13-28%], adjusted P=2*10^-12 ) and longer PFS (14.2 [95% CI 10.7-20.3] versus 5.4 months [95% CI 4.5-7.0], adjusted P=2*10^-9 ) than East-Asians/Hispanics/Africans in NAC/UP subtypes. Caucasian ethnicity remained independently associated with higher ORR (OR 4.10, 95% CI 2.48-6.81, adjusted P=2*10^-7 ) and longer PFS (HR 0.58, 95% CI 0.46-0.74, adjusted P=4*10^-5 ) in multivariate analyses after adjustment for age, sex, primary anatomic location, M stage, baseline lactate dehydrogenase (LDH) level, mutational status, and prior systemic treatment. Whereas Caucasians and East-Asian/Hispanics/Africans shared similar ORR/PFS in acral/mucosal/uveal melanomas. Similar melanoma-subtype-specific ethnic discrepancies were observed in complete response rate and overall survival. Caucasians had higher rates of GI but lower rates of endocrine/liver/other-rare-types of irAEs. These differences in irAEs by ethnicity were not attributable to varying melanoma subtypes.

Conclusions

Ethinic discrepancy in clinical benefit is melanoma subtype-specific, East-Asians/Hispanics/Africans with NAC/UP melanomas have poorer clinical benefits than previously recognized. Ethinic discrepancy in toxicity observed across different melanoma subtypes warrants an ethinicity-based irAE surveillance strategy. More research is needed to elucidate the molecular and immunologic determinants of these differences.