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. 2024 Jun;13(12):e7302.
doi: 10.1002/cam4.7302.

Treatment patterns and survival outcomes of patients admitted to the intensive care unit due to immune-related adverse events of immune checkpoint inhibitors

Lishi Lin  1 , Aletta P I Houwink  2 , Jolanda M van Dieren  3 , Esther K Wolthuis  2 , Johannes V van Thienen  4 , Michiel S van der Heijden  4 , John B A G Haanen  4   5   6 , Jos H Beijnen  1   7 , Alwin D R Huitema  1   8   9
Affiliations

Treatment patterns and survival outcomes of patients admitted to the intensive care unit due to immune-related adverse events of immune checkpoint inhibitors

Lishi Lin et al. Cancer Med. 2024 Jun.

Abstract

Introduction: Severe immune-related adverse events (irAEs) due to immune checkpoint inhibitors (ICIs) can lead to admission to the intensive care unit (ICU). In this retrospective study, we determined the incidence, treatment patterns and survival outcomes of this patient population at a comprehensive cancer center.

Methods: All patients admitted to the ICU due to irAEs from ICI treatment between January 2015 and July 2022 were included. Descriptive statistics were reported on patient characteristics and treatment patterns during hospital admission. Overall survival (OS) from the time of ICU discharge to death was estimated using the Kaplan-Meier method.

Results: Over the study period, 5561 patients received at least one ICI administration, of which 32 patients (0.6%) were admitted to the ICU due to irAEs. Twenty patients were treated with anti-PD-1 plus anti-CTLA-4 treatment, whereas 12 patients were treated with ICI monotherapy. The type of irAEs were de novo diabetes-related ketoacidosis (n = 8), immune-related gastrointestinal toxicity (n = 8), myocarditis or myositis (n = 10), nephritis (n = 3), pneumonitis (n = 2), and myelitis (n = 1). The median duration of ICU admission was 3 days (interquartile range: 2-6 days). Three patients died during ICU admission. The median OS of the patients who were discharged from the ICU was 18 months (95% confidence interval, 5.0-NA).

Conclusion: The incidence of irAEs leading to ICU admission in patients treated with ICI was low in this study. ICU mortality due to irAEs was low and a subset of this patient population even had long-term survival.

Keywords: immune checkpoint inhibitors; immune‐related adverse events; intensive care unit; survival.

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Conflict of interest statement

L. Lin, A.P.I. Houwink, J.M. van Dieren, E.K. Wolthuis, J.V. van Thienen and A.D.R. Huitema declare no conflict of interest. M.S. van der Heijden has received research grants (paid to the institute) from BMS, AstraZeneca, Roche and 4SC and has served as an advisor (fees paid to the institute) to Roche, Pfizer, Astellas, Astra Zeneca, Merck Sharp and Dome, BMS, and Janssen. J.B.A.G. Haanen reports an advisory role for AZ, Achilles Therapeutics, BioNTech, Bristol‐Myers Squibb, CureVac, Imcyse, Immunocore, Instil Bio, Iovance Biotherapeutics, Ipsen, Molecular Partners, MSD Oncology, Neogene Therapeutics, Novartis, PokeAcell, Roche/Genentech, Sanofi, Scenic, Third Rock Ventures and T‐Knife; has received research funding (paid to the institute) from Amgen, Asher Biotherapeutics, BioNTech, Bristol‐Myers Squibb, MSD, Neon Therapeutics, Novartis, Sastra Cell Therapy; and is stock owner of Neogene Therapeutics. J.H. Beijnen is a part‐time employee and (indirect) shareholder of Modra Pharmaceuticals BV. He is (partly) patent holder of oral taxane formulations which are clinically developed by Modra Pharmaceuticals BV (a spin‐off company of the Netherlands Cancer Institute), not related to this work.

Figures

FIGURE 1
FIGURE 1
Overview of treatment course of patients administered to the intensive care unit (ICU) due to immune‐related adverse events of immune checkpoint inhibitors (ICIs) in days. One row represents one patient: the x‐axis shows time in days in which the black arrow indicates that the current ICI treatment was initiated longer ago. Previous and current ICI: type of ICI administered including the number of administrations. Atezolizumab (A), durvalumab (DU), ipilimumab (I), nivolumab (N), nivolumab + ipilimumab (NI), pembrolizumab (P). SOFA: SOFA score in the first 24 h of ICU stay (SOFA 24) and highest score during (first) ICU stay (SOFA H). SP: support in the form of mechanical ventilation (V), renal replacement therapy (R), and plasmapheresis (F). FU: follow‐up information including death during ICU stay (D), readmission (RA), and rechallenge with ICI (RC). OS: overall survival of patients discharged from the ICU in months with ‘+’ indicating that the patient was censored.
FIGURE 2
FIGURE 2
Overall survival (OS) of (A) patients from the time of intensive care unit (ICU) discharge till death and (B) patients without de novo diabetes‐related ketoacidosis. CI, confidence interval; NA, not available.
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