Study Suggests Link Between Complement, ICANS in B-Cell Non-Hodgkin Lymphomas

A retrospective study’s findings suggest that in patients with B-cell non-Hodgkin lymphoma who have undergone chimeric antigen receptor (CAR) T-cell therapy, there is an association between post-CAR-T terminal complement complex levels, namely sC5b-9, and immune effector cell-associated neurotoxicity syndrome (ICANS) experienced after CAR-T. These findings were presented at the 2024 ASCO® Annual Meeting.

Complement activation is proposed to be behind the endothelial dysfunction, which leads to ICANS, and the investigators mentioned complement as a potential therapeutic target.

The study cohort was 42 patients with B-cell non-Hodgkin lymphomas, 36 who had been treated with axicabtagene ciloleucel and six with brexucabtagene autoleucel from March 2022 to September 2023. The researchers collected data on these patients’ pre lymphodepletion, pre-CAR-T, and post-CAR-T infusion sC5b-9 levels. They defined clinically significant ICANS as having a peak grade of 2 or higher.

Regarding ICANS occurrence in the cohort following CAR-T, 57% did not experience ICANS, while 10% of patients had ICANS of peak grade 4, 5% had peak grade 3, 14% had peak grade 2, and 14% had peak grade 1. The median time from CAR-T to ICANS peak was six days.

The investigators then examined the pre lymphodepletion, pre-CAR-T, and post-CAR-T sC5b-9 levels on record for all the patients, and compared the figures from the patients who had ICANS of peak grade 2 or higher against those from patients with ICANS of peak grade 1 or who did not experience ICANS.

Between these two patient groups, the investigators found no statistical difference in pre lymphodepletion or pre-CAR-T sC5b-9 levels, but post-CAR-T sC5b-9 levels were significantly higher.

“We found that the post-CAR-T sC5b-9 levels were significantly higher among [patients] who had ICANS [of peak grade 2 or higher].”

Over the course of the study the investigators had also measured pre lymphodepletion lactate dehydrogenase, post-CAR-T ferritin, and post-CAR-T fibrinogen, and found no statistically significant difference between the two patient groups.

Regarding cytokine release syndrome (CRS) occurrence among the patients following CAR-T, 38% had a peak grade of 2, 52% had a peak grade of 1, and 10% did not experience CRS.

Reference

Durisek G, Zhao Q, Voorhees T, et al. Association between post-CART terminal complement complex (TCC) levels and clinically significant immune effector cell–associated neurotoxicity syndrome (ICANS). Abstract #7036. Presented at the 2024 ASCO® Annual Meeting; May 31-June 4, 2024; Chicago, Illinois