Comprehensive real-world and clinical trial data demonstrate that lisocabtagene maraleucel (liso-cel; Breyanzi) maintains a favorable safety profile across blood cancer settings, with most severe adverse events occurring within a predictable timeframe and resolving without intensive interventions, according to findings presented at the 2025 American Society of Clinical Oncology Annual Meeting.
The analysis pooled data from 702 patients enrolled in five clinical trials and 877 patients treated in real-world settings through the Center for International Blood and Marrow Transplant Research Registry, representing one of the largest safety datasets for this CD19-directed CAR-T therapy.
Predictable Timing of Adverse Events
In the clinical trial population, 60% of patients experienced cytokine release syndrome (CRS) or neurological events (NEs), with 96% of these events occurring within 15 days following liso-cel infusion. Among the 18 patients who experienced CRS or NE onset after day 15, all events were grade 1/2 severity only.
Real-world data from the CIBMTR Registry showed similar patterns, with 53% of patients experiencing CRS or immune effector cell-associated neurotoxicity syndrome (ICANS), and 96% of events occurring within 15 days after infusion. Of 18 patients with late-onset events after day 15, most were grade 2, with only 2 patients experiencing grade 3 or higher events.
The median time to onset was consistent across settings. In clinical trials, CRS occurred at a median of 5 days (range, 1-63) and NEs at 8 days (range, 1-63). Real-world data showed CRS onset at a median of 4 days (range, 1-554) and ICANS at 6 days (range, 1-30).
Manageable Late-Onset Events
For patients experiencing late-onset adverse events, management was typically straightforward. In the clinical trial setting, 71% of patients with CRS onset after day 15 required standard hospitalization, with none needing intensive care unit-level care. The most common interventions included tocilizumab (57%) and corticosteroids (29%).
Among patients with late-onset neurological events in clinical trials, 93% (25 of 27 patients) had their toxicities managed in the outpatient setting without hospitalization, with corticosteroids serving as the primary intervention in 26% of cases.
Real-world data showed even more favorable outcomes for late-onset events. All evaluable cases of CRS after day 15 resolved without hospitalization, and no grade 4/5 events occurred in this timeframe. For patients with late-onset ICANS in the real-world setting, 50% required management with corticosteroids.
Consistent Safety Across Indications
The study included patients with relapsed/refractory large B-cell lymphoma, chronic lymphocytic leukemia, small lymphocytic lymphoma, follicular lymphoma, and mantle cell lymphoma. The median patient age was 65.0 years in clinical trials and 70.6 years in the real-world population.
"Data from the liso-cel pivotal clinical trials and the real-world standard-of-care setting from the CIBMTR Registry were consistent and demonstrated that most CRS/ICANS/NEs occurred within 15 days after liso-cel infusion and were not severe," wrote lead study author Manali Kamdar, MD, MBBS, from the University of Colorado Cancer Center, with coauthors.
Implications for Clinical Practice
The researchers noted that no grade 5 neurological events or CRS occurred in the clinical trial setting. In the CIBMTR Registry, 11 patients had grade 5 CRS and/or ICANS, but all occurred within 15 days after infusion, reinforcing the predictable timing of severe events.
The findings have important implications for optimizing patient monitoring strategies. "These results reinforce the established safety profile of liso-cel across indications and can inform optimal monitoring requirements after infusion to suit patient needs and improve access to treatment, without compromising safety," the authors concluded.
The data support the potential for tailored monitoring approaches that could reduce healthcare resource utilization while maintaining patient safety, particularly for managing patients beyond the critical first two weeks post-infusion when severe events are most likely to occur.
