Delayed immune toxicities in patients with breast cancer receiving immune checkpoint inhibitors.

Abstract

e24091 Background: Immune checkpoint inhibitors (ICI) have improved outcomes in patients with breast cancer, however management of immune-related adverse events (irAE) remains a challenge. Delayed irAE after cessation of ICI have been observed. We sought to characterize delayed irAE occurring at our center. Methods: We identified patients with breast cancer who received ICI at UCSF using ICD codes specific to ICI administration between 2012-2018. After IRB approval, charts were reviewed for delayed irAE. Delayed irAE were defined as occurring >60 days after the last ICI dose; events were counted as irAE if provider notes indicated that the toxicity was/possibly was related to ICI. Data were securely stored using RedCap. Results: We reviewed 100 consecutive patients who underwent ICI (56 metastatic, 44 localized) of which 11 (2 (4%) with metastatic disease, 9 (20.5%) with localized disease) developed delayed irAE. Median age was 42. 3 patients had HR+ disease, 8 patients had triple negative disease. 10 patients received ICI on a clinical trial, including 9 on the neoadjuvant ISPY2 trial. 10 patients received pembrolizumab; 1 received durvalumab. Median number of ICI doses was 4, median follow-up time after last ICI infusion was 46 months. 14 incidences of delayed irAEs were identified (Table). 9 patients experienced both delayed and early irAE. 7 patients experienced 2 irAEs: 1) three dermatitis & delayed hypophysitis/adrenal insufficiency (AI) 2) one AI & delayed thyroiditis 3) one dermatitis and delayed colitis 4) one elevated transaminases & delayed colitis 5) one delayed elevated transaminases and delayed thyroiditis. One patient had 3 irAEs (thyroiditis, delayed AI & delayed arthralgia) and one patient had 4 irAE (colitis, dermatitis, delayed elevated transaminases & delayed neutropenia). Of the 9 patients with > 1 irAE, 3 experienced > 1 delayed irAE (thyroiditis + elevated transaminases; arthralgia + AI; elevated transaminases + neutropenia). All irAE either self-resolved, resolved with systemic steroids or indefinite hormone replacement. 6 irAEs required systemic steroids, not including hydrocortisone replacement for AI. Conclusions: Delayed irAE may occur months after ICI cessation and require awareness for identification. Patients who experience irAE may be more likely to develop additional irAE at either a delayed or earlier time point. Most patients with delayed irAE experienced an irAE at an early time point. Future directions include identifying risk factors for early and delayed irAEs to inform treatment decisions. [Table: see text]