Prognostic significance of immune-related adverse events and immunosuppression in patients with melanoma receiving adjuvant anti-PD-1 therapy.

Abstract

9580 Background: Treatment with anti-Programmed Death-1 (PD-1) therapy reduces the risk of recurrence for patients (PT) with resectable Stage IIB-IV melanoma (MEL). This treatment is associated with the development of immune-related adverse events (irAEs), which may necessitate use of immunosuppressive therapy and treatment discontinuation. This project investigates the impact of irAE and immunosuppressive therapy in survival outcomes of PTs with MEL. Methods: PTs with stage IIB-IV resectable MEL who received adjuvant or neoadjuvant treatment with anti-PD-1 therapy were enrolled from the University of Pittsburgh Melanoma Center biospecimen repository. The association between irAEs/immunosuppressive therapy and recurrence-free survival (RFS) and overall survival (OS) were evaluated by univariate and multivariate Cox proportional hazards regression models. Results: A total of 6059 PT were consented to the repository: stage III = 1,328, stage IIB = 403, and stage IIC = 269 PT. Of these PT, 180 men and 93 women received adjuvant anti-PD-1 therapy. Average age at diagnosis was 61. BRAF mutation present in 94 PTs: V600E = 71 PT, V600K = 11 PT. Documented irAEs occurred in 50.9% of PTs. Cutaneous irAEs were most common (65/139, 46.8%), followed by endocrine (45/139 32.4%), and visceral organ (37/139, 26.6%). Of the 32 visceral organ irAEs, 15 were gastrointestinal, 10 pulmonary, 5 hepatic, and 1 renal. Systemic corticosteroids > 10mg of prednisone equivalent were administered during adjuvant therapy for 24.9% of PT. In the univariate model, development of irAEs was associated with improved OS (HR = 0.38; CI 0.18-0.83, p = 0.015). In a multivariate analysis after adjusting for age and sex, irAE development continued to be associated with improved OS (HR = 0.38; CI 0.17-0.82, p = 0.014). RFS did not differ for patients that developed irAEs (HR = 0.9; CI 0.59-1.4, p = 0.67). Steroid treatment was not associated with a change in OS (HR = 1.04; CI 0.46-2.4, p = 0.93) or RFS (HR = 0.96; CI 0.59-1.56, p = 0.87). Conclusions: Half of stage IIB-IV resectable MEL PT receiving adjuvant anti-PD1 therapy developed irAEs, of which 24% required steroid therapy. Development of irAE was associated with improved OS and corticosteroid use for irAE did not mitigate adjuvant therapy outcome benefits.