Long-term mortality outcomes among immunotherapy recipients treated with dupilumab for the management of cutaneous immune-related adverse events.

BACKGROUND

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.

METHODS

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.

RESULTS

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).

CONCLUSIONS

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.