The phase 2 clinical trial investigating Sobi's anakinra (Kineret) as a preventive measure against CAR T-cell therapy complications has yielded disappointing results, failing to meet its primary endpoint of reducing cytokine release syndrome (CRS) in patients with large B-cell lymphoma (LBCL).
Trial Design and Implementation
The study, presented at the 2025 Tandem Meetings in Honolulu, enrolled 25 LBCL patients receiving lisocabtagene maraleucel (liso-cel, Breyanzi). Participants received anakinra either subcutaneously (15 patients) or intravenously (10 patients) at 200 mg daily for 14 days post-infusion. The IV group had access to step-up dosing options of 8 mg/kg/day in divided doses or 1 mg/kg/hour continuous infusion for 72 hours if toxicities worsened.
Key Efficacy Findings
The results showed that 68% of anakinra-treated patients developed CRS, with 90% occurrence in the IV group and 53% in the subcutaneous group. This compared unfavorably to the historical control group, where 63% of patients receiving liso-cel alone experienced CRS. ICANS occurred in 36% of anakinra-treated patients versus 34% in the control group.
"Our primary end point of reducing any-grade CRS to 15% was not met," stated Dr. Emily Liang from Fred Hutch Cancer Center during her presentation. She noted that real-world CRS rates were higher than those observed in the TRANSCEND trial, which had reported a 40% incidence.
Safety and Secondary Outcomes
Anakinra demonstrated a favorable safety profile with no treatment-related adverse events. However, researchers observed some infections: two cases of mild Clostridium difficile in the subcutaneous group and one case of cytomegalovirus reactivation in the IV group.
The study revealed some positive secondary findings: anakinra-treated patients required lower cumulative dexamethasone doses (10 vs 27) and shorter steroid courses (median 3 days vs 6 days) compared to liso-cel alone. However, the need for tocilizumab remained similar between groups.
Impact on Treatment Response
A concerning finding emerged regarding treatment efficacy. The overall response rate in the anakinra cohort was 74% compared to 80% in the liso-cel alone group. Complete response rates were notably lower with anakinra (42% vs 51%), with the IV cohort showing the lowest CR rate at 38%. These results raise questions about anakinra's potential interference with CAR T-cell functionality.
Future Directions
Despite the disappointing primary outcome, Dr. Liang emphasized the importance of further research: "Further studies are needed to assess whether there might be greater benefit of prophylactic anakinra in patients with a higher risk of toxicities."
Researchers are now conducting correlative studies to understand anakinra's effects on CAR T-cell kinetics and inflammatory pathways. The findings underscore the ongoing challenge of managing CAR T-cell therapy complications while maintaining treatment efficacy.
