Combined programmed cell death protein 1 and cytotoxic T-lymphocyte associated protein 4 blockade in an international cohort of patients with acral lentiginous melanoma.
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McGillivray Erin, Ashouri Karam, Chatziioannou Eftychia, Gallegos Jesús Antonio Ocejo, Zarka Jabra, Kechter Jacob, Hwang Angelina S, Zhang Kevin, Barros Milton, Yeh Justin, Okazaki Ian, Crocker Andrew B, Maeda Takuya, Park Soo J, Choi Jacob, Andreoli Mia, Darwish Tarneem, Savage David J, Kim Kevin B, Gupta Jayant, Shen James, Shirai Keisuke, Choi April, Pai Lori, Vazquez Vinicius de Lima, Moser Justin, Amaral Teresa, Hernandez Aya Leonel F, Lutzky Jose, Najjar Yana G, Costello Collin M, Mangold Aaron R, Bhatia Shailender, Gibney Geoffrey T, Farma Jeffrey M, Daniels Gregory A, Sosman Jeffrey, Chandra Sunandana, Mangla Ankit, Bollin Kathryn, Possik Patrícia Abrão, Robles-Espinoza Carla Daniela, Ito Fumito, In Gino K
Аннотация
OBJECTIVES: To determine the efficacy of combination immune checkpoint blockade targeting PD-1 and CTLA-4 in a diverse, real-world population of patients with ALM.
METHODS: This multi-institutional retrospective study analysed patients with histologically confirmed ALM treated with a combination of PD-1 and CTLA-4 inhibitors between 2010 and 2022. The primary objective of the study was the objective response rate (ORR) as per the RECIST criteria. The secondary objectives were progression-free survival (PFS) and overall survival (OS).
RESULTS: In total, 109 patients with advanced ALM treated with combined PD-1 and CTLA-4 blockade in any line of treatment were included. The majority of patients had stage IV disease (n = 81; 74.3%). The ORR for the entire cohort was 18.3% [95% confidence interval (CI) 11.6-26.9], with 9 (8.3%) complete and 11 (10.1%) partial responses. A further 22 patients (20.2%) had stable disease, and the disease control rate was 38.5%. Median PFS was 4.2 months (95% CI 3.25-5.62), while median OS was 17 months (95% CI 12.4-23.1). Ninety-five patients (87.2%) had a treatment-related adverse event, with 40.4% (n = 44/109) experiencing at least one grade 3 or 4 toxicity. Elevated lactate dehydrogenase (P = 0.04), ≥ 2 lines of prior treatment (P = 0.03) and Asian ethnicity (P = 0.04) were associated with worse OS, while Hispanic/Latino ethnicity was associated with better OS (P = 0.02).
CONCLUSIONS: Combination PD-1 and CTLA-4 blockade is less effective for ALM than for CM, despite similar toxicity. In particular, Asian patients appear to derive less benefit from this regimen. Novel treatment approaches are needed for this rare melanoma subtype.