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

Laura X. Wang, Henry T. Quach, Nikil V. Moodabigil, Elizabeth J. Davis, Jeffrey A. Sosman, Stacie B. Dusetzina, Douglas B. Johnson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Background: 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. Methods: 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. Results: 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). Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)322-328
Number of pages7
Journalcancer
Volume126
Issue number2
DOIs
StatePublished - Jan 15 2020

Funding

Elizabeth J. Davis receives research funding from Incyte, Bristol‐Myers Squibb, Genentech, Five Prime, and Karyopharm. Jeffrey A. Sosman serves on advisory boards for Bristol‐Myers Squibb, Incyte, Genentech, and Curis and reports personal fees from Bristol‐Myers Squibb, MSD, and Array. Douglas B. Johnson serves on advisory boards for Array Biopharma, Bristol‐Myers Squibb, Incyte, Merck, and Novartis; reports travel support from Genentech; and receives research funding from Bristol‐Myers Squibb and Incyte. The other authors made no disclosures. This study was supported by the National Cancer Institute/National Institutes of Health (K23 CA204726 to Douglas B. Johnson), the National Institutes of Health (R01CA227481), the James C. Bradford Jr Melanoma Fund (to Douglas B. Johnson), the American Cancer Society (institutional review grant to Douglas B. Johnson), and the Melanoma Research Foundation (to Douglas B. Johnson).

Keywords

  • death
  • health care utilization
  • immune
  • infliximab
  • ipilimumab
  • nivolumab
  • pembrolizumab
  • steroid
  • toxicity

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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