Katja Schindler

Monoclonal antibodies (mAb) targeting immune checkpoint pathways such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1) may confer durable disease control in several malignancies. In some patients, immune checkpoint mAbs cause cutaneous immune-related adverse events. Although the most commonly reported cutaneous toxicities are mild, a subset may persist despite therapy and can lead to severe or life-threatening toxicity. Autoimmune blistering disorders are not commonly associated with immune checkpoint mAb therapy. We report a case series of patients who developed bullous pemphigoid (BP), an autoimmune process classically attributed to pathologic autoantibody formation and complement deposition. Three patients were identified. Two patients developed BP while receiving the anti-PD-1 mAb nivolumab, and one while receiving the anti-PD-L1 mAb durvalumab. The clinicopathologic features of each patient and rash, and corresponding radiologic findings at the development of the rash and after its treatment, are described. Patients receiving an anti-PD-1/PD-L1 mAb may develop immune-related BP. This may be related to both T-cell- and B-cell-mediated responses. Referral to a dermatologist for accurate diagnosis and management is recommended. Cancer Immunol Res; 4(5); 383-9. ©2016 AACR.

9096 Background: Ipilimumab (ipi) has shown significant improvements in overall survival (OS) for patients (pts) with advanced melanoma in randomized phase III trials. Easily obtainable pre- or on-treatment biomarkers would be helpful to optimize this therapy. In a prior analysis, IL-17 levels correlated with immune-related adverse events (irAEs), and IL-17 and eosinophils are immunologically related. In one prior single institution study of 73 ipi-treated pts, an increase in absolute eosinophil count (AEC) was associated with improved OS. Whether this finding correlates with other clinical outcomes such as immune-related adverse events (irAEs) or is reproducible in larger, multicenter analyses remains unknown. Methods: 156 pts with advanced melanoma treated with ipi at the approved standard dose of 3mg/kg in 4 institutions (Medical University of Vienna, University of Zurich, University of Lausanne, and Memorial Sloan-Kettering Cancer Center) between 2010 and 2013 were retrospectively analyzed. Baseline (B/L), week (W) 4 and W7 absolute and relative eosinophil (AEC and REC) counts and occurrence of irAEs were noted. Wilcoxon rank-sum test was performed for analyzing the association of AEC and REC with irAEs. OS was calculated from date of first ipi dose to date of death or last followup. The association between B/L, W4 and W7 levels of AEC and REC and OS was assessed using Cox proportional hazards regression. Results: The change in AEC from B/L to W4 and from B/L to W7 was significantly associated with the occurrence of any irAE (p=0.032 and p=0.007, respectively). As continuous variables at W4, AEC and REC were significantly associated with irAEs (p=0.018 and p=0.275, respectively). At W7 AEC was significantly associated with irAEs (p=0.019) but REC was not (p=0.074). Neither AEC nor REC at B/L was significantly associated with irAEs. Neither the change in AEC nor REC from B/L to W4 was associated with OS. Conclusions: Eosinophils were associated with irAEs but not OS during ipi treatment. Given functional links between IL-17 and eosinophils, and the correlation of both IL-17 and eosinophils with irAEs, further study of the mechanistic role of this pathway in pts with irAEs is warranted.