Dr Kamdar on the Safety Profile of Liso-Cel Across Patient Subgroups in MCL

Manali Kamdar, MD, associate professor, medicine, hematology-oncology; clinical director, Lymphoma Services, University of Colorado Anschutz School of Medicine, discusses common toxicities associated with lisocabtagene maraleucel (liso-cel; Breyanzi) across patient subgroups from a post-hoc subgroup analysis of the mantle cell lymphoma (MCL) cohort of the phase 1 TRANSCEND NHL 001 trial (NCT02631044). She also discusses proposed next steps for evaluating the clinical utility of liso-cel in relapsed/refractory MCL.

Results from this analysis, which assessed responses to liso-cel in patients with MCL based on prior lines of therapy and previous exposure to BTK inhibitors, were presented at the 2024 EHA Congress. Liso-cel demonstrated clinically meaningful activity across all subgroups, with response rates comparable with those seen in the overall population of 88 patients, indicating consistent efficacy in a variety of clinical backgrounds.

Notably, safety was also favorable across subgroups, which provided added reassurance, particularly with respect to treatment-emergent adverse effects associated with CAR T-cell therapy. Cytopenia was more prevalent in patients who had received over 5 prior lines of treatment, underscoring the impact of cumulative therapy on blood counts. However, unique CAR T-related toxicities, such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, were consistent across lines of treatment and showed no differences based on BTK inhibitor refractoriness.

This durable response profile was especially encouraging for patients who had progressed on two or more prior lines of MCL treatment, achieving robust and sustained responses without an increased risk of severe toxicity. Importantly, these results extended across age cohorts, adding confidence in the treatment's safety for both older and younger patients alike. Looking forward, continued follow-up of these patients will be essential to assess the long-term durability of responses. Additionally, these findings support the potential to investigate liso-cel in earlier treatment lines, which could expand its use and possibly improve outcomes for patients at initial stages of MCL.