Understanding the Effects of Post-irAE Treatments With Immunosuppressant Agents in Cancer Immunotherapy

Authors: Pierre-Louis Cariou, Cédric Pobel, Jean-Marie Michot, François-Xavier Danlos, Benjamin Besse, Franck Carbonnel, Xavier Mariette, Aurélien Marabelle, Sabine Messayke, Caroline Robert, Emilie Routier, Nicolas Noël, Olivier Lambotte

Accepted to be published in the European Journal of Cancer, on April 2024

Introduction:

Immune checkpoint blockers (ICBs) have revolutionized cancer treatment, but their use can lead to serious immune-related adverse events (irAEs). Management of irAEs often involves the use of steroids and/or immunosuppressant (IS) agents, which raises concerns about potentially reducing the effectiveness of ICBs. This study aimed to investigate the relationship between the use of steroids and/or ISs and overall survival (OS) and progression-free survival (PFS) among ICB-treated patients with an irAE.

Design/Methods:

In this study conducted by Gustave Roussy Cancer Center, researchers utilized the REISAMIC registry to prospectively analyze the impact of immune checkpoint blockade (ICB) therapy on patients with solid tumors or lymphoma between June 2014 and June 2020. The cohort was divided into three groups based on their post-immune-related adverse event (irAE) treatment: Group A(n=57) received no steroids or immunosuppressants, Group B  (n=107) received only steroids, and Group C(n=20)  received immunosuppressants, possibly combined with steroids. Key outcomes measured were overall survival, progression-free survival, and a safety profile that included hospital admissions and infections. Data was collected on various parameters such as demographic characteristics, type of cancer, immunotherapy specifics, and adverse event grades. Statistical analyses, including survival analysis and multivariate testing, were conducted using R software, with the primary focus on determining differences in survival outcomes and the safety profile across the three groups.

What We Learned:

The median OS was significantly shorter for patients in Group B (25.2 months) compared to Groups A (63 months) and C (53.4 months) (p<0.001). Similarly, the median PFS was significantly shorter for Group B (17.0 months) compared to Groups A (33.9 months) and C (41.1 months) (p=0.006). These findings persisted even after adjusting for potential confounders such as ECOG performance status, irAE grade, and cancer type.

Key Highlights:

• The use of immunosuppressant agents (e.g., infliximab, methotrexate) was not associated with worse OS or PFS, in contrast with the use of steroids alone for the management of irAEs.
• There were no significant differences in hospital admission and infection rates among the three groups.
• 9 irAE-related deaths were due to immune-related pneumonitis, all occurring in Group B (steroids alone).

Key Takeaway Messages:

• In this prospective cohort, the use of IS was not associated with worse outcomes, suggesting that it may be a safe and effective option for managing irAEs.
• The use of steroids alone for irAE management was associated with shorter OS and PFS, highlighting the need for careful consideration of steroid use and potential alternatives, such as IS agents.
• Further research is needed to confirm these findings and optimize the management of irAEs to improve outcomes for cancer patients treated with ICBs.

Summary by Amalya Sargsyan, MD

Impact of immunosuppressive agents on the management of immune-related adverse events of immune checkpoint blockers

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