Prophylactic Anakinra Prevents CRS, ICANS in Patients With LBCL Receiving CAR T-cells

A phase 2 study of prophylactic anakinra, an IL-1 receptor inhibitor, intended to prevent cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) and mantle cell lymphoma (MCL) who receive commercial CD19 chimeric antigen receptor (CAR) T-cells.

“CD19 CAR T-cells have demonstrated high response rates in R/R lymphoma, but these therapies are associated with high rates of CRS and ICANS, often requiring prolonged hospital stays including transfer to the ICU. We have previously reported IL-1 inhibition prevented developments of severe ICANS and CRS in the in vivo preclinical model,” explained Jae Park, MD, Memorial Sloan Kettering Cancer Center, New York, and co-authors.

A total of 31 patients were enrolled to the study. CD19 CAR products included axicabtagene for 23 patients, tisagenlecleucel for 4 patients, and brexucabtagene for 4 patients. Out of all the patients, 17 reported prior exposure to bridging therapy to T-cell infusion. All patients started anakinra at 100mg every 12 hours. Further, dose escalation of anakinra increased to 100mg every 6 hours in 13 patients. The reported median duration of anakinra administration was 10 days.

“CRS of all grades was observed in 21 patients, with severe CRS (grade 3 to 4) in 2 patients. Median CRS duration was 5.5 days. ICANS of all grades was observed in 4 patients, with severe ICANS in 2 patients. No patients experienced grade 5 CRS or ICANS. Tocilizumab and corticosteroids were used in 9 patients and 6 patients, respectively,” continued Dr Park and co-authors.

Three patients required ICU transfer. In 23 patients with LBCL treated with axicabtagene, both severe CRS and ICANS were observed in 4% with tocilizumab and steroid use in 22% and 13%, respectively.

A median follow-up of 104 days (range 21-363) was reported. Overall disease response rate at month 1 was 74% for all patients with a complete response (CR) rate at 1 and 3 months of 58% and 52%, respectively.

“Early use of IL-1 receptor inhibitor anakinra appears to be safe and feasible and reduces the rates of both severe CRS and ICANS with the comparable response rates in patients with R/R LBCL receiving CD19 CAR T-cells. A longer follow-up is needed to assess durability of remission, but the study provides strong support for continued investigation of IL-1 inhibition in prevention of severe ICANs,” concluded Dr Park, et al.—Alexa Stoia

Park J, Sauter C, Palomba M, et al. A Phase II Study of Prophylactic Anakinra to Prevent CRS and Neurotoxicity in Patients Receiving CD19 CAR T Cell Therapy for Relapsed or Refractory Lymphoma. Presented at: the 2021 ASH Annual Meeting; Dec. 11-14; 2021; Abstract 96.