No Significant Reduction of CRS or ICANS Seen With Sobi's Anakinra in Patient's Receiving Liso-Cel for LBCL
The data, which comes from a phase 2 trial, were presented at the 2025 Tandem Meetings.
This article originally appeared on our sister site, OncLive®.
Sobi's anakinra (marketed as Kineret) did not significantly reduce the incidence or severity of cytokine release syndrome (CRS) or immune effector cell–associated neurotoxicity syndrome (ICANS) in patients receiving Bristol Myers Squibb's chimeric antigen receptor T-cell (CAR-T) therapy lisocabtagene maraleucel (liso-cel; marketed as Breyanzi) for the treatment of large B-cell lymphoma (LBCL). These results come from a phase 2 clinical trial (NCT04359784), data from which were presented at the 2025 Tandem Meetings |Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, held in Honolulu, Hawaii, February 12 to 15, 2025.
The trial's primary end point, which constituted a lowering of CRS rates, was not met. Although, anakinra was noted to have been well-tolerated in the study.
Furthermore, even though intravenous (IV) administration of anakinra appeared to cut down the duration of ICANS, the drug was not able to prevent toxicity progression and was associated with lower complete response (CR) rates.
“We observed that prophylactic anakinra, including IV dosing with up-titration, was feasible and safe," Emily Liang, MD, of Fred Hutch Cancer Center, said in the oral presentation of the findings given at the conference. "However, our primary end point of reducing any-grade CRS to 15% was not met. This end point was based on a benchmark from a clinical trial, where conditions may not exactly match real-world settings. In fact, in our non-trial patient cohort receiving liso-cel alone, we observed a CRS rate of 63% compared with 40% in the TRANSCEND study [NCT02631044].”
The phase 2 trial enrolled 25 patients with LBCL receiving liso-cel.
Participants in the trial, which included 25 patients receiving liso-cel for LBCL, were given anakinra either subcutaneously (SC; n = 15) or via IV infusion (n = 10) at a dose of 200 mg daily from Day 0 through Day 13 following infusion. Step-up dosing was allowed in the patients receiving anakinra through IV infusion in cases of worsening CRS or ICANS:
- 8 mg/kg/day IV in 3 divided doses
- 1 mg/kg/hour continuous infusion for 72 hours
ASTCT criteria were utilized to monitor for CRS and ICANS. ICANS severity, hospitalization rates, steroid use, and overall response rates served as secondary end points for the trial. A retrospective comparison to outcomes for 72 patients who had received liso-cel alone at the same institution was also included as part of the study.
Although the trial screened 32 patients in total, only 25 were treated with liso-cel and anakinra. It was noted that the group that received anakinra and the control group had comparable baseline disease burdens, histologic subtypes, and pretreatment inflammatory markers.
No interruptions of the planned dosing regimen occurred in the patients receiving anakinra. With regard to safety, there were no adverse events deemed related to anakinra. Although, in the SC cohort, 2 cases of mild Clostridium difficile infections were reported, and in the IV cohort 1 case of cytomegalovirus reactivation was recorded.
Key Findings
Seventeen patients (68%) treated with anakinra (SC: 53%; IV: 90%) experienced cases of CRS. On the other hand, 47 (63%) of the patients from the retrospective cohort who received liso-cel alone experienced cases of CRS. Furthermore, 9 patients (36%) who received anakinra experienced cases of ICANS, whereas 25 patients (34%) in the control group experienced ICANS cases. Cases of grade 2 or higher CRS and grade 3 or higher ICANS appeared at similar rates across the groups.
“Of note, no patients who received IV and anakinra developed grade 3 or higher ICANS, despite having the highest rate of CRS at 90%, though we acknowledge the small numbers in this group,” Liang added.
IV dosing was associated with lower ICANS severity and shorter duration at a median of 2 days vs 5 days in controls. Although, step-up dosing did not prevent CRS progression from grade 1 to grade 2 in patients requiring escalation.
A total of 8 patients developed CRS. Two patients required up-titration to step-up dose number 1 only, and 5 patients required up-titration to step-up dose number 2. For all cases of CRS, up-titration to step-up dose number 2 did not prevent progression from grade 1 to grade 2.
While the need for tocilizumab and steroids was similar across groups, anakinra-treated patients required lower cumulative dexamethasone doses (10 vs 27) and shorter steroid courses at a median of 3 days (IQR, 2-5.5 days) vs 6 days (IQR 3-11 days) with liso-cel alone. Nine patients in the liso-cel plus SC or IV anakinra arm required tocilizumab vs 22 patients in the liso-cel only arm.
In addition, anakinra was linked to lower CR rates. Overall response rates (ORR) were 74% in the anakinra cohort vs 80% in the liso-cel alone group, and CR rates were 42% in anakinra-treated patients vs 51% in the control group. In the IV cohort, CR rates were lowest at just 38%.
“Our primary end point of any grade CRS reduction to 15% was not met. However, our end point was based on a benchmark from a clinical trial where conditions may not exactly match real-world conditions. In fact, in our non-trial patient cohort of liso-cel only, we observed a CRS rate of 63% compared with 40% in the TRANSCEND study,” added Liang.
Implications and Next Steps
While anakinra prophylaxis was well-tolerated and did not lead to treatment-related adverse events, it failed to reduce CRS or ICANS incidence. The finding that IV anakinra was associated with lower CR rates raises concerns about its potential impact on CAR T-cell function and persistence.
Researchers are now focusing on correlative studies to understand anakinra’s effects on CAR T-cell kinetics and inflammatory pathways. These findings highlight the need for alternative strategies to mitigate CAR T-cell toxicities, particularly for high-risk patients. Future research will also explore other immune-modulating agents and refined patient selection criteria for toxicity prevention.
“Further studies are needed to assess whether there might be greater benefit of prophylactic anakinra in patients with a higher risk of toxicities,” concluded Liang.
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