Health care utilization and steroid-refractory toxicities from immune checkpoint inhibitors

Anti-programmed death protein 1 (anti-PD-1) agents have transformed the treatment of advanced melanoma and other cancers, but the rates of steroid-refractory toxicities and health care utilization are not well described. This study assessed these endpoints in patients with melanoma treated with anti-PD-1 with or without ipilimumab.

This study retrospectively evaluated 344 patients with metastatic melanoma treated with anti-PD-1 or a combination of ipilimumab and nivolumab at Vanderbilt University Medical Center from 2009 to 2018. The incidence, types, grades, management, and outcomes of immune-related adverse events (irAEs) and hospitalizations for irAEs and disease progression were assessed.

Patients on combination therapy were more likely to develop irAEs than those on monotherapy (72% vs 37%; P < .001) and were more likely to require systemic steroids (61% vs 20%; P < .001), steroid dose re-escalation (23% vs 6%; P < .001), and second-line immunosuppressive use (17% vs 2%; P < .001) and to suffer high-dose steroid-refractory toxicities (23% vs 3%; P < .001). Combination-treated patients were more likely to have any hospitalization (32% vs 7%; P < .001) or multiple hospitalizations for irAEs (11% vs 3%; P = .001) and had a longer average time of hospitalization (mean, 1.92 vs 0.62 days; P = .002). Among 176 hospitalizations related to disease progression in patients who died during evaluable follow-up, 69% occurred within the 90 days before death. Early hospitalizations for disease-related reasons portended a very poor prognosis (median time from admission to death, 58 days).

Patients treated with a combination of ipilimumab and nivolumab had higher rates of hospitalization and steroid-refractory toxicities than those treated with anti-PD-1 monotherapy. Disease-associated hospitalizations were similar between the 2 groups, portended a poor prognosis, and mostly occurred in the last months of life.