肢端雀斑样痣黑色素瘤国际患者队列中程序性细胞死亡蛋白1与细胞毒性T淋巴细胞相关蛋白4联合阻断治疗
Combined programmed cell death protein 1 and cytotoxic T-lymphocyte associated protein 4 blockade in an international cohort of patients with acral lentiginous melanoma.
作者信息
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
机构信息
Department of Medicine, USC Keck School of Medicine, Los Angeles, CA, USA.
Division of Oncology, USC Keck School of Medicine, USC Norris Cancer Hospital, Los Angeles, CA, USA.
出版信息
Br J Dermatol. 2025 Jan 24;192(2):316-326. doi: 10.1093/bjd/ljae401.
BACKGROUND
Combination immune checkpoint blockade targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) leads to high response rates and improved survival in patients with advanced cutaneous melanoma (CM). Less is known about the efficacy of this combination in acral lentiginous melanoma (ALM).
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.
背景
靶向程序性细胞死亡蛋白1（PD-1）和细胞毒性T淋巴细胞相关蛋白4（CTLA-4）的联合免疫检查点阻断疗法可使晚期皮肤黑色素瘤（CM）患者获得高缓解率并改善生存率。关于这种联合疗法在肢端雀斑样痣黑色素瘤（ALM）中的疗效，人们了解较少。
目的
确定在不同的真实世界ALM患者群体中，靶向PD-1和CTLA-4的联合免疫检查点阻断疗法的疗效。
方法
这项多机构回顾性研究分析了2010年至2022年间接受PD-1和CTLA-4抑制剂联合治疗的组织学确诊为ALM的患者。该研究的主要目标是根据RECIST标准的客观缓解率（ORR）。次要目标是无进展生存期（PFS）和总生存期（OS）。
结果
总共纳入了109例在任何治疗线中接受PD-1和CTLA-4联合阻断治疗的晚期ALM患者。大多数患者为IV期疾病（n = 81；74.3%）。整个队列的ORR为18.3%[95%置信区间（CI）11.6 - 26.9]，其中9例（8.3%）完全缓解，11例（10.1%）部分缓解。另有22例患者（20.2%）病情稳定，疾病控制率为38.5%。中位PFS为4.2个月（95%CI 3.25 - 5.62），而中位OS为17个月（95%CI 12.4 - 23.1）。95例患者（87.2%）发生了与治疗相关的不良事件，40.4%（n = 44/109）经历了至少一次3级或4级毒性反应。乳酸脱氢酶升高（P = 0.04）、既往治疗≥2线（P = 0.03）和亚洲人种（P = 0.04）与较差的OS相关，而西班牙裔/拉丁裔人种与较好的OS相关（P = 0.02）。
结论
尽管毒性相似，但PD-1和CTLA-4联合阻断疗法对ALM的疗效低于对CM的疗效。特别是，亚洲患者似乎从该治疗方案中获益较少。这种罕见的黑色素瘤亚型需要新的治疗方法。
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