Real-World Data Show Most CRS, ICANS Cases Happen Within 15 Days of Liso-Cel Infusion

The risk of cytokine release syndrome (CRS) and immune effector cell-mediated neurotoxicity syndrome (ICANS) dropped significantly 15 days following infusion of lisocabtagene maraleucel (liso-cel [Breyanzi; Bristol Myers Squibb]) in a recent study published in Transplantation and Cellular Therapy.¹ The report offers important insights for clinicians and regulators as they consider monitoring requirements for the expanding roster of chimeric antigen receptor (CAR) T-cell therapies.

The risk of neurological events, including CRS or ICANS, in patients receiving CAR T-cell therapies generally means that patients who receive the therapy must receive daily monitoring for several days following infusion and remain within close proximity of a health care facility for weeks.

However, as use of the drug in real-world settings expands, regulators have shown a willingness to reconsider such strictures. In June, the FDA updated the requirements for patients receiving liso-cel and another CAR-T therapy, idecabtagene vicleucel (ide-cel [Abecma; Bristol Myers Squibb]). Among the changes, the agency reduced driving restrictions on patients following treatment and said they only need to stay near a hospital for 2 weeks after infusion instead of 4 weeks.²

The new report supports the timeline change.¹ Corresponding author Bradley D. Hunter, MD, of Intermountain LDS Hospital, and colleagues, sought to use real-world data to look at the onset, grade, and duration of CRS and ICANS/neurological events.¹

The investigators used 2 data sources. First, they used clinical trial data for 702 patients who received liso-cel as a participant in one of 5 clinical trials across various B-cell non-Hodgkin lymphomas. In addition, they used data from the Center for International Blood and Marrow Transplant Research’s (CIBMTR) Registry, which includes 877 patients who received liso-cel for B-cell lymphoma.

The 2 data sources yielded similar results. Fifty-four percent of the clinical trial patients experienced CRS of any grade, and only 1% had grade 3 or above CRS at onset. In the real-world data set, 49% had any grade of CRS, and only 3% hit a maximum grade of 3 or above. However, 98% of patients with CRS in the clinical trial cohort experienced onset within 15 days, similar to the 97% rate in the real-world cohort.

Among clinical trial participants, 31% experienced any-grade neurological events, of which 5% were grade 3 or above at onset. Eighty-eight percent of those participants experienced neurological event onset within 15 days of infusion. In the real-world data set, 27% of patients had any-grade ICANS, and 10% had a maximum grade of 3 or above. Among the 150 patients for whom onset dates were available, 95% of patients had onset within 15 days.

Across the cohorts, median times to resolution ranged from 4 days to 7 days.

“These results support the recent updates from the FDA reducing the requirement for patients to remain close to the health care facility from 4 weeks to 2 weeks after infusion,” Hunter and colleagues wrote.

The findings will not only help patients who are already planning to receive the CAR T-cell therapy, the authors noted; they will also likely enable more patients to receive the therapy.

“The previous monitoring requirements were believed to disadvantage patients of lower socioeconomic status and those who live far from major CAR T-cell therapy treatment centers (I.D. the rural-urban divide) due to the costs and time of travel, lodging, and loss of income due to relocation for infusion,” they wrote.

However, Hunter and colleagues said that clinicians will need to respond to the FDA update—and to the results of this analysis—by updating their own post-infusion monitoring strategies for patients with relapsing or remitting B-cell malignancies who receive liso-cel. Their data suggest that such strategies can be changed without a significant negative impact on patient safety.

References

1. Hunter BD, Lunning M, Shadman M, et al. CRS or ICANS are rare beyond 2 weeks after lisocabtagene maraleucel infusion: data from clinical trials and the real-world setting. Transplant Cell Ther. Published online October 24, 2025. doi:10.1016/j.jtct.2025.10.024
2. U.S. Food and Drug Administration approves streamlined patient monitoring requirements and removal of REMS programs within Bristol Myers Squibb's cell therapy labels. News release. Bristol Myers Squibb. Published June 26, 2025. Accessed November 22, 2025. https://news.bms.com/news/corporate-financial/2025/U-S--Food-and-Drug-Administration-Approves-Streamlined-Patient-Monitoring-Requirements-and-Removal-of-REMS-Programs-within-Bristol-Myers-Squibbs-Cell-Therapy-Labels/default.aspx