The IL-1 inhibitor anakinra can prevent severe cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in patients with relapsed or refractory lymphoma receiving chimeric antigen receptor (CAR) T-cell therapy, a phase 2 study suggests.
“Our study … validates that IL-1 is an important and valid target to prevent severe CRS and ICANS related to CD19 CAR T cells,” said Jae Park, MD, of Memorial Sloan Kettering Cancer Center in New York, New York.
Dr Park presented results from the study (ClinicalTrials.gov Identifier: NCT04148430) at the 2021 American Society of Hematology (ASH) Annual Meeting.
Dr Park and colleagues tested anakinra in 31 patients with relapsed or refractory lymphoma who received commercially available CD19 CAR-T cells. The patients’ median age was 62 years (range, 25-77 years).
The patients had diffuse large B-cell lymphoma (DBCL, n=68), transformed follicular lymphoma (n=16), mantle cell lymphoma (MCL, n=13), and primary mediastinal B-cell lymphoma (n=3).
For CAR T-cell therapy, 74% of patients received axicabtagene, 13% received tisagenlecleucel, and 13% received brexucabtagene.
The patients also received anakinra at 100 mg subcutaneously every 12 hours starting either on day 2 of CAR T-cell infusion of after 2 consecutive fevers. Anakinra was continued at least until day 10. Doses could be increased to 100 mg every 6 hours, and the duration of treatment could continue beyond day 10.
Patients could receive tocilizumab and/or corticosteroids if they had persistent or worsening CRS and neurotoxicity.
The rate of any-grade CRS was 74% overall, 78% in axicabtagene recipients, 75% in brexucabtagene recipients, and 50% in tisagenlecleucel recipients.
There was 1 case of grade 3 CRS, 1 case of grade 4 CRS, and no cases of grade 5 CRS. Grade 3 CRS was reported in a patient who had received axicabtagene, and grade 4 CRS was seen in a patient who received brexucabtagene.
The rate of any-grade ICANS was 19% overall, 33% in brexucabtagene recipients, 22% in axicabtagene recipients, and 0% in tisagenlecleucel recipients.
There were no cases of grade 4 or 5 ICANS. Grade 3 ICANS was observed in 2 patients who received axicabtagene and 1 patient who received brexucabtagene.
In all, 29% of patients received tocilizumab (n=9), and 19% received corticosteroids (n=6). Dr Park noted this these percentages are lower than those seen in prior trials.
Dr Park also noted that response rates in this trial were comparable to those in other trials of CD19 CAR T-cell products. The objective response rate (ORR) was 78% overall, and 68% of patients had a complete response (CR) as their best response. At month 3, the CR rate was 58%.
Among patients with DLBCL, the ORR was 74%, and the CR rate was 63%. Among patients with MCL, the CR rate was 100%.
“We believe that anakinra represents an attractive toxicity prevention and mitigation strategy, especially for high-risk patients,” Dr Park concluded.
Disclosures: This study was sponsored by Memorial Sloan Kettering Cancer Center. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
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Park JH, Sauter CS, Palomba L, 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 ASH 2021; December 11-14, 2021. Abstract 96.