Multi-institutional analysis of incidence and risks for late-onset immune toxicity in breast cancer.

Immune checkpoint inhibitors (ICI) improve survival in triple-negative breast cancer (TNBC) but cause late-onset toxicity, with unknown incidence in breast cancer. This retrospective study included 700 patients (61%, n = 424 early-stage; 39%, n = 276 metastatic; 77% TNBC) from four NCI-designated centers treated with ICI between 2014-2021. Chart review identified immune toxicities, defined as ICI-related, as noted by the oncology provider or steroid-treated. 61% (n = 430) had toxicity: 37% (n = 257) early (≤90 days after ICI start), 34% (n = 240) delayed (>90 days), 10% (n = 67) both. Of the delayed, 144 (60%) were on-treatment, 56 (23%) off-treatment, 40 (17%) both. Twenty-two (9.2%) had off-treatment toxicity >1 year post-ICI. Median onset: 138 days (range 90-1380) on-treatment; 76 days (21-1144) off-treatment. Risk increased with more ICI cycles, especially >4 (early OR 1.104; metastatic OR 1.06; p < 0.0001) and higher baseline eosinophils (OR 3.46, p = 0.0484). Metastatic disease (OR 0.18, p < 0.0001) and early toxicity (OR 0.53, p = 0.0008) reduced risk. Findings support the need for high clinical suspicion for late toxicity.