Lisocabtagene maraleucel (liso-cel; Breyanzi), a CD19-directed CAR T-cell therapy, continues to demonstrate substantial efficacy across multiple lymphoma subtypes, with new data highlighting its potential for expanded use in earlier treatment lines.
Strong Activity in Mantle Cell Lymphoma
Data from the mantle cell lymphoma (MCL) cohort of the phase 1 TRANSCEND NHL 001 trial, presented at the 2024 EHA Congress, showed encouraging results in heavily pretreated patients. Among 26 patients who received 5 to 11 prior lines of therapy, liso-cel achieved a median duration of response of 6.7 months (95% CI, 2.4-15.8), a median progression-free survival of 7.4 months (95% CI, 3.3-12.3), and a median overall survival of 13.5 months (95% CI, 9.5-17.1).
"Responses in this subgroup were comparable with those seen in the overall population (n = 83); clinically meaningful activity with liso-cel was observed across all subgroups," noted Dr. Manali Kamdar, associate professor of medicine in hematology-oncology and clinical director of Lymphoma Services at the University of Colorado Anschutz School of Medicine.
Exceptional Results in Follicular Lymphoma
The therapy has shown particularly impressive outcomes in follicular lymphoma patients. "Especially with follicular lymphoma, the response rates are just stellar. The median follow up is a little under 3 years right now, but at this point in time, the median duration of response and responders [are great]," Dr. Kamdar explained.
She emphasized the durability of responses, stating, "Personally, for the people I enrolled on the trials, they're all in a complete remission, they've gone back to life, they have not relapsed. They're young patients and older patients across all age groups."
Current Approval and Treatment Landscape
Liso-cel is currently approved for second- and third-line treatment of diffuse large B-cell lymphoma (DLBCL) and third-line treatment for follicular lymphoma and MCL. The approval is based on data from the phase 3 TRANSFORM and TRANSCEND trials, which demonstrated the therapy's superiority over standard of care in relapsed/refractory large B-cell lymphoma.
Updated 3-year data from the TRANSFORM trial was presented at the 2024 ASCO Annual Meeting, continuing to show deep and durable responses in patients with relapsed/refractory large B-cell lymphoma.
Potential for Earlier Treatment Lines
Dr. Kamdar advocates for exploring liso-cel's use in earlier treatment settings, particularly given that less heavily pretreated patients may have better-preserved T-cell health. For DLBCL, she specifically highlights high-risk subgroups that could benefit from earlier intervention.
"In the context of DLBCL, particularly among high-risk subgroups—such as patients with high-grade B-cell lymphomas, double-hit lymphomas, or those who achieve only a partial remission on interim PET scans in combination with high-risk cytogenetics—liso-cel should be considered for use in earlier lines of treatment," Dr. Kamdar emphasized.
Addressing Unmet Needs in Mantle Cell Lymphoma
For MCL, Dr. Kamdar noted that significant unmet medical needs persist, especially for aggressive cases. "In MCL, an unmet need persists for effective treatments, especially for cases with aggressive features, such as those proliferative in nature, those enriched with TP53 mutations, or those with blastoid and pleomorphic phenotypes," she explained.
She believes expanding CAR T-cell therapy use beyond third-line treatment could yield exceptional results. "Expanding the use of CAR T-cell therapy, including liso-cel, beyond the third line and into the second-line setting may yield exceptional response rates and durability of remission," Dr. Kamdar said.
The manageable toxicity profile of liso-cel in earlier treatment lines makes this an exciting area for continued exploration in MCL therapy, according to Dr. Kamdar's assessment.
