Khattab Sara, Wan Guihong, Xu Suzanne, Moseley Cameron, Tran Matthew, Beagles Emma, Lin Chuck, Leung Bonnie W, Azin Marjan, Hao Ninghui, Reynolds Kerry L, Demehri Shadmehr, LeBoeuf Nicole R, Semenov Yevgeniy R
Dermatology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, USA.
J Immunother Cancer. 2025 May 12;13(5):e010638. doi: 10.1136/jitc-2024-010638.
Dupilumab has been added to National Cancer Comprehensive Network guidelines as a therapeutic strategy for managing certain cutaneous immune-related adverse events (cirAEs) from immune checkpoint blockade (ICB). However, little is known about the implications of dupilumab for cancer outcomes in this population. In this multi-institutional study, we evaluate the impact of dupilumab treatment on survival among ICB recipients.
We conducted a multi-institutional retrospective cohort study of ICB recipients from the Mass General Brigham Healthcare System and Dana-Farber Cancer Institute. The dupilumab group was compared with two control groups who did not receive dupilumab: with and without cirAEs (control groups 1 and 2, respectively) that were 1:2 matched on sex, race, age at ICB initiation, Charlson Comorbidity Score, year of ICB initiation, and ICB type. Manual chart review was performed to obtain cirAE characteristics, systemic glucocorticoid use, dupilumab treatment, vital status, and last contact date. Time-varying multivariable Cox proportional hazards regressions were used to evaluate the impact of dupilumab on overall survival, adjusted for sex, race, age at ICB initiation, ICB type, Charlson Comorbidity Index score, cancer type, cancer stage at ICB initiation, and systemic glucocorticoid use.
A total of 53 cirAE patients treated with dupilumab were compared with two control groups of 106 patients each. Most patients receiving dupilumab demonstrated either complete or partial resolution of their cirAE (88.7%). In multivariable modeling, the overall survival of the dupilumab group was not significantly different from control group 1 (HR=0.74, 95% CI: 0.35 to 1.60, p=0.5) or control group 2 (HR=0.70, 95% CI: 0.32 to 1.51, p=0.4). However, the use of systemic glucocorticoids within 2 years after ICB initiation was associated with poorer overall survival when comparing the dupilumab group to control group 1 (HR=2.03, 95% CI: 1.04 to 3.96, p=0.039) and control group 2 (HR=2.21, 95% CI: 1.25 to 3.91, p=0.006).
This study suggests that dupilumab is an effective therapy for recalcitrant cirAEs and does not adversely impact mortality. Due to the observed detrimental effects of systemic glucocorticoid therapy, this study suggests the need to shift away from systemic glucocorticoid immunosuppression and toward targeted immune modulators for irAE management, though prospective randomized trials are necessary to investigate this.
度普利尤单抗已被纳入美国国立综合癌症网络指南，作为治疗免疫检查点阻断（ICB）引发的某些皮肤免疫相关不良事件（cirAE）的一种治疗策略。然而，对于度普利尤单抗对该人群癌症预后的影响知之甚少。在这项多机构研究中，我们评估了度普利尤单抗治疗对接受ICB治疗患者生存情况的影响。
我们对来自麻省总医院布莱根医疗系统和丹娜 - 法伯癌症研究所的ICB治疗患者进行了一项多机构回顾性队列研究。将度普利尤单抗组与两个未接受度普利尤单抗的对照组进行比较：有和没有cirAE的对照组（分别为对照组1和对照组2），两组在性别、种族、开始ICB治疗时的年龄、查尔森合并症评分、开始ICB治疗的年份和ICB类型方面按1:2进行匹配。通过人工查阅病历获取cirAE特征、全身糖皮质激素使用情况、度普利尤单抗治疗情况、生命状态和最后联系日期。使用时变多变量Cox比例风险回归评估度普利尤单抗对总生存的影响，并对性别、种族、开始ICB治疗时的年龄、ICB类型、查尔森合并症指数评分、癌症类型、开始ICB治疗时的癌症分期和全身糖皮质激素使用情况进行了调整。
共有53例接受度普利尤单抗治疗的cirAE患者与两个各有106例患者的对照组进行比较。大多数接受度普利尤单抗治疗的患者cirAE表现为完全或部分缓解（88.7%）。在多变量模型中，度普利尤单抗组的总生存与对照组1（风险比[HR]=0.74，95%置信区间[CI]：0.35至1.60，p = 0.5）或对照组2（HR = 0.70，95% CI：0.32至1.51，p = 0.4）相比无显著差异。然而，与对照组1（HR = 2.03，95% CI：1.04至3.96，p = 0.039）和对照组2（HR = 2.21，95% CI：1.25至3.91，p = 0.006）相比，在开始ICB治疗后2年内使用全身糖皮质激素与较差的总生存相关。
本研究表明度普利尤单抗是治疗顽固性cirAE的有效疗法，且不会对死亡率产生不利影响。由于观察到全身糖皮质激素治疗的有害作用，本研究提示需要从全身糖皮质激素免疫抑制转向针对irAE管理的靶向免疫调节剂，不过这需要前瞻性随机试验来进行研究。
