Liso-cel May Show Benefit in Earlier Therapy Lines for Lymphoma Subgroups

In a conversation with CancerNetwork^® at the 2024 European Hematology Association (EHA) Congress, Manali Kamdar, MD, highlighted the potential next steps for researching lisocabtagene maraleucel (liso-cel; Breyanzi) in subgroups of patients with mantle cell lymphoma (MCL) and other types of lymphoma.

Kamdar, an associate professor of Medicine-Hematology and clinical director of Lymphoma Services at the University of Colorado Anschutz Medical Campus, discussed this possible future research in the context of findings from subgroup analysis findings from the phase 1 TRANSCEND NHL 001 trial (NCT02631044) that she presented as a poster at the meeting. In this analysis, she and her coauthors concluded that the efficacy and safety of liso-cel improved in patients who received fewer than 5 prior lines of therapy as well as those with disease not refractory to prior Bruton tyrosine kinase inhibitor use, supporting the agent’s use in earlier lines of treatment.

Kamdar suggested that future research could focus on the utility of liso-cel in diffuse large B-cell lymphoma (DLBCL) subgroups such as those with high-grade disease or double-hit lymphoma. Additionally, MCL may remain a potential area of focus for the agent among patients with aggressive phenotypes or TP53-mutated disease.

Transcript:

Liso-cel is a CD19 CAR T-cell therapy that has shown good efficacy in some hard-to-treat lymphomas like diffuse large B-cell lymphoma [DLBCL], follicular lymphoma, and mantle cell lymphoma. It’s approved in all those settings. They have all been approved in the third-line or second-line setting.

In the diffuse large B-cell lymphoma space, [liso-cel] probably needs to be tested even in the earlier lines of treatment. Maybe [it can be tested] in a high-risk diffuse large B-cell lymphoma subgroup like high-grade B cell lymphomas, double-hit lymphomas, patients who have a partial remission on an interim PET with high-risk cytogenetics or FISH. Those are the patients who would potentially be better suited for liso-cel in the earlier lines of treatment.

On the other hand, with mantle cell lymphoma, I do believe that the space for liso-cel needs to continue to be explored. Mantle cell lymphoma remains an unmet need, especially if it’s proliferative, enriched with TP53 mutations, [and has] aggressive phenotypes like blastoid and pleomorphic. If CAR T-cell therapy is brought in even beyond the third-line setting—maybe in the second-line setting—I am quite convinced that the durability of responses would be exceptional. I do believe that the toxicity would be manageable.

Reference

Palomba ML, Siddiqi T, Gordon LI, et al. Subgroup analyses in patients with R/R MCL treated with lisocabtagene maraleucel by prior lines of therapy and response to Bruton tyrosine kinase inhibitor from the TRANSCEND NHL 001 MCL cohort. Presented at the European Hematology Association (EHA) 2024 Hybrid Congress; Madrid, Spain; June 13-16, 2024. P1126.