Severe Immune-Related Adverse Events Associated with Durable Antitumor Responses Following Immune Checkpoint Inhibitor Therapy: Two Case Reports.

Abstract

Background: Immune checkpoint inhibitors (ICIs) have achieved remarkable success in treating advanced cancers, yet the accompanying immune-related adverse events (irAEs) pose a major challenge to their clinical application. Growing evidence suggests an association between irAEs and improved clinical outcomes; however, the heterogeneity in this relationship warrants further exploration.

Case presentation: This article reports two cases of patients with advanced cancer who achieved long-term disease control after experiencing severe irAEs. Case one involved a patient with heavily pretreated Luminal B1 advanced breast cancer who developed Grade 3 immune-related arrhythmia and heart failure following treatment with Toripalimab combined with chemotherapy. Case two involved a patient with ROS1-fusion advanced lung adenocarcinoma who, after developing resistance to Crizotinib, received chemotherapy and Tislelizumab, leading to Grade 3 immune-related hypopituitarism, adrenal insufficiency, and cutaneous toxicity. Both patients were managed with corticosteroids with or without immunosuppressants and discontinued all antitumor therapies. Despite this, they have achieved a partial response (PR) with a duration of response (DoR) of 22 and 37 months, respectively, and both responses are ongoing at the time of this report.

Conclusion: In this series, two patients with advanced solid tumors achieved durable tumor responses after developing severe irAEs and discontinuing treatment, suggesting that severe irAEs may herald the establishment of long-term immune memory. However, the association between irAEs and efficacy is not straightforward, as the type and severity of irAEs and the use of immunosuppressive intervention all influence the ultimate clinical benefit. In the absence of reliable predictive biomarkers, clinical decisions should not equate irAEs directly with efficacy markers; rather, the benefits and risks of immune activation should be carefully weighed.