Evaluating Survival After Hospitalization Due to Immune-Related Adverse Events From Checkpoint Inhibitors

Abstract

Background: As immune checkpoint inhibitors (CPI) are increasingly approved for cancer treatment, hospitalizations related to severe immune-related adverse events (irAE) will increase. Here, we identify patients hospitalized due to irAEs and describe survival outcomes across irAE, CPI, and cancer type.

Methods: We identified patients hospitalized at our institution from January 2012 to December 2020 due to irAEs. Survival was analyzed using Kaplan-Meier survival curves with log-rank tests.

Results: Of 3137 patients treated with CPIs, 114 (3.6%) were hospitalized for irAEs, resulting in 124 hospitalizations. Gastrointestinal (GI)/hepatic, endocrine, and pulmonary irAEs were the most common causes of irAE-related hospitalization. After CPI initiation, the average time to hospitalization was 141 days. Median survival from hospital admission was 980 days. Patients hospitalized due to GI/hepatic and endocrine irAEs had longer median survival than patients with pulmonary irAEs (795 and 949 days vs. 83 days [P < .001]). Patients with melanoma and renal cell carcinoma had longer median survival than patients with lung cancer (2792 days and not reached vs. 159 days [P < .001]). There was longer median survival in the combination group compared to the PD-(L)1 group (1471 vs. 529 days [P = .04]).

Conclusions: As CPI use increases, irAE-related hospitalizations will as well. These findings suggest that among patients hospitalized for irAEs, survival differs by irAE and cancer type, with worse survival for patients with irAE pneumonitis or lung cancer. This real-world data contributes to research pertaining to hospitalization due to severe irAEs, which may inform patient counseling and treatment decision-making.

Keywords: cancer; hospitalization; immune checkpoint inhibitors; immunotherapy; irAE.

Figure 1.

Inclusion criteria for the study cohort.

Figure 2.

(A) Distribution of cancer type for patients hospitalized for immune-related adverse events (irAEs). (B) Distribution of Hospitalized irAEs. In parenthesis, the number per irAE describes the total number of hospitalizations combining hospitalizations for single-system irAE with multisystem irAEs. For example, for cardiovascular there were 4 hospitalizations for cardiac irAE alone and 10 hospitalizations with cardiac irAEs combined with other system irAEs. A hospitalization within 1 system could have multiple specific irAEs within that system in 1 hospitalization. Number of hospitalizations in italics describe irAE hospitalizations with only that system.

Figure 3.

(A) Overall survival from time of hospitalization of the entire cohort. (B) Overall survival of immune-related adverse event (irAE)-related hospitalizations by irAE type. (C) Overall survival for irAE-related hospitalizations by cancer type. (D) Overall survival of patients hospitalized for irAE by checkpoint inhibitor type. A sensitivity analysis was performed with the same models but excluded patients with non-metastatic disease which had similar results to the overall cohort (Supplementary Figs. 4A–4D).