Safety and efficacy of retreatment with immune checkpoint inhibitors after severe immune-related adverse events

Area of Science:

• Oncology
• Immunology
• Clinical Medicine

Background:

• Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but can cause severe immune-related adverse events (irAEs).
• The safety and effectiveness of re-administering ICIs after severe irAEs are not well-established.

Purpose of the Study:

• To evaluate the safety and efficacy of retreatment with ICIs in patients who previously experienced severe irAEs.
• To assess the incidence and characteristics of irAE recurrence or new-onset irAEs upon ICI retreatment.

Main Methods:

• Retrospective analysis of 1271 cancer patients treated with ICIs from September 2014 to June 2023.
• Evaluation of severe irAEs (grade ≥3) and subsequent ICI retreatment in 46 patients (excluding single endocrinopathies).

Main Results:

• Severe irAEs occurred in 17.5% of patients; 30.4% of those retreated experienced recurrent or new grade ≥2 irAEs.
• Objective response rate to ICI retreatment was 28.3%, with 10.9% complete and 17.4% partial responses.
• At one year post-retreatment, 15.4% discontinued due to irAEs, while 33.4% continued treatment.

Conclusions:

• ICI retreatment after severe irAEs presents a manageable safety profile and encouraging efficacy, even for grade ≥3 events.
• This strategy may be a valuable option for patients with limited alternatives, especially if they responded well to initial ICI therapy.