Nykaza Ian, Moy Andrea, Dusza Stephen W, Moskowitz Alison, Iyer Gopa, Iqbal Afsheen, Motzer Robert, Ilson David H, O'Cearbhaill Roisin E, Kazi Rashek, Defazio Jennifer, Gordon Allison, Markova Alina
Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States.
Department of Dermatology, Weill Cornell Medical College, New York, NY 10021, United States.
Oncologist. 2025 Sep 1;30(9). doi: 10.1093/oncolo/oyaf208.
Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy but are associated with treatment-limiting immune-related cutaneous adverse events (irCAEs). Immune checkpoint inhibitor-related bullous pemphigoid (irBP), a severe, blistering irCAE occurs in 0.3%-1.5% of patients receiving ICI therapy. While systemic steroids can be effective, they are associated with significant toxicity and may mitigate -immunotherapy antitumor efficacy. Consequently, steroid-sparing therapies are needed. Dupilumab, an IL-4 and IL-13 receptor antagonist, has demonstrated efficacy in non-ICI-related BP and appears promising for managing irBP.
We conducted a retrospective review of patients treated with dupilumab for irBP from April 2020 to April 2024. Clinical data, outcomes, and adverse events were assessed. Inhibitor-related bullous pemphigoid response was categorized as complete response (CR), partial response (PR), or no response (NR).
In all, 17 patients (59% male, 82% non-Hispanic White; mean age 72.7 years) developed irBP while receiving PD-1/PDL-1 inhibitors. Sixteen patients (94%) received dupilumab for active irBP and one (6%) for prevention of recurrence. Dupilumab achieved CR of irBP for 12 patients (75%) and PR for 2 (12%) patients with active irBP. Ten (62%) achieved CR with dupilumab systemic monotherapy. Median time to first response was 19.5 days (range = 3-50). Most patients with CR (58%) failed prior oral corticosteroid therapy. The patient treated prophylactically experienced no irBP recurrence. Dupilumab was well-tolerated, with no adverse events.
Dupilumab is a promising steroid-sparing option for irBP, achieving initial response in under 20 days for most cases. Dupilumab is a valuable tool to manage this challenging irCAE while minimizing risk related to systemic steroid treatment.
免疫检查点抑制剂(ICIs)彻底改变了癌症治疗方式,但与限制治疗的免疫相关皮肤不良事件(irCAEs)有关。免疫检查点抑制剂相关的大疱性类天疱疮(irBP)是一种严重的水疱性irCAE,在接受ICI治疗的患者中发生率为0.3%-1.5%。虽然全身用类固醇可能有效,但它们具有显著的毒性,并且可能会降低免疫治疗的抗肿瘤疗效。因此,需要采用节省类固醇的疗法。度普利尤单抗是一种白细胞介素-4和白细胞介素-13受体拮抗剂,已在非ICI相关的类天疱疮中显示出疗效,并且在治疗irBP方面似乎很有前景。
我们对2020年4月至2024年4月期间接受度普利尤单抗治疗irBP的患者进行了回顾性研究。评估了临床数据、治疗结果和不良事件。将抑制剂相关的大疱性类天疱疮反应分为完全缓解(CR)、部分缓解(PR)或无反应(NR)。
共有17名患者(59%为男性,82%为非西班牙裔白人;平均年龄72.7岁)在接受PD-1/PDL-1抑制剂治疗时发生了irBP。16名患者(94%)因活动性irBP接受了度普利尤单抗治疗,1名患者(6%)接受度普利尤单抗以预防复发。度普利尤单抗使12名活动性irBP患者(75%)的irBP达到CR,2名患者(12%)达到PR。10名患者(62%)通过度普利尤单抗全身单一疗法达到CR。首次缓解的中位时间为19.5天(范围=3-50天)。大多数达到CR的患者(58%)先前口服皮质类固醇治疗无效。接受预防性治疗的患者未出现irBP复发。度普利尤单抗耐受性良好,未出现不良事件。
度普利尤单抗是一种很有前景的用于治疗irBP的节省类固醇的选择,大多数病例在20天内即可获得初始缓解。度普利尤单抗是管理这种具有挑战性的irCAE的宝贵工具,同时将与全身类固醇治疗相关的风险降至最低。