Anakinra Manages ICANS/CRS Toxicity Induced by CAR T-Cell Therapy

Nicolas Gazeau, MS, postdoctoral research scholar at Fred Hutchinson Cancer Center, discusses a retrospective study of anakinra (Kineret) for the management of neurotoxicity and cytokine release syndrome (CRS) in patients who have received chimeric antigen receptor (CAR) T-cell therapy.

Immune effector cell–associated neurotoxicity syndrome (ICANS) and CRS are significant adverse events associated with CAR T-cell therapy, and research into treatments with more efficacy than corticosteroids is ongoing. A retrospective study of patients with B-cell or plasma malignancies investigated 43 patients who received anakinra. Some were given 100 mg to 200 mg per day subcutaneously (SC) and some were given a higher dose of 8 mg/kg per day SC or intravenously (IV).

The study showed faster improvement of ICANS/CRS toxicity in the high-dose group and a lower rate of non-relapse mortality in those who received a high dose of anakinra. Gazeau concluded that anakinra showed efficacy in managing these toxicities, especially with the higher dose.

When reporting on the results for 26 patients in November 2021, investigators observed ICANS/CRS improvement in 73% of patients with a median duration of treatment of 3 days. The response rate based on physician’s evaluation of symptom improvement was 100% in those who received a higher dose versus 46% in the lower-dose group. Anti-tumor response from CAR T-cell therapy was also higher in the high-dose group. A shorter time to initiation of anakinra was associated with CRS/ICANS improvement. Non-relapse mortality at day 30 was also significantly lower in those who received a higher dose at 69% versus 0% with a lower dose (P = .001).

TRANSCRIPTION:

0:08 | We separated the cohort of 43 into 2 different groups. Some patients received low dose-anakinra between 100 mg and 200 mg a day, and some of the patients received a high-dose of anakinra, so we called these groups low and high dose. High dose was around 8 mg/kg a day. We first showed that there was no difference between the peak of CRS and the peak of ICANS between the 2 groups, from time to first anakinra or even a steroid duration. We showed faster resolution of CRS or ICANS in the high-dose group, and we also showed a lower rate of non-relapse mortality in the high-dose group. The result at the end is anakinra seems to have efficacy on ICANS and CRS after CAR T-cell therapy. This efficacy looks more pertinent and more interesting when we treat patients with high dose.