Prophylactic Anakinra Reduces Severe Neurotoxicity to Under 10% in CAR T-Cell Therapy for Lymphoma
A phase 2 trial evaluated prophylactic anakinra, an IL-1 receptor antagonist, in 31 patients receiving commercial anti-CD19 CAR T-cell therapy for relapsed or refractory lymphoma. Severe ICANS occurred in only 9.7% of patients with no grade 4 or 5 events, a marked reduction compared to historical rates, while maintaining a 77% overall response rate with 65% complete responses. These results suggest that IL-1 pathway blockade can meaningfully reduce the most feared neurological complication of CAR T therapy without compromising anti-tumour efficacy.
The original study
CD19 CAR T-cell therapy and prophylactic anakinra in relapsed or refractory lymphoma: phase 2 trial interim results.
- Authors
- Park JH, Nath K, Devlin SM, Sauter CS, Palomba ML, Shah G, et al.
- Journal
- Nature medicine
- Type
- Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
- PMID
- 37400640
Original abstract
In preclinical models, anakinra, an IL-1 receptor antagonist (IL-1Ra), reduced immune effector cell-associated neurotoxicity syndrome (ICANS) without compromising anti-CD19 chimeric antigen receptor (CAR) T-cell efficacy. We initiated a phase 2 clinical trial of anakinra in patients with relapsed/refractory large B-cell lymphoma and mantle cell lymphoma treated with commercial anti-CD19 CAR T-cell therapy. Here we report a non-prespecified interim analysis reporting the final results from cohort 1 in which patients received subcutaneous anakinra from day 2 until at least day 10 post-CAR T-cell infusion. The primary endpoint was the rate of severe (grade ≥3) ICANS. Key secondary endpoints included the rates of all-grade cytokine release syndrome (CRS) and ICANS and overall disease response. Among 31 treated patients, 74% received axicabtagene ciloleucel, 13% received brexucabtagene ciloleucel and 4% received tisagenlecleucel. All-grade ICANS occurred in 19%, and severe ICANS occurred in 9.7% of patients. There were no grade 4 or 5 ICANS events. All-grade CRS occurred in 74%, and severe CRS occurred in 6.4% of patients. The overall disease response rate was 77% with 65% complete response rate. These initial results show that prophylactic anakinra resulted in a low incidence of ICANS in patients with lymphoma receiving anti-CD19 CAR T-cell therapy and support further study of anakinra in immune-related neurotoxicity syndromes.