FDA Approves Lisocabtagene Maraleucel for Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

On March 14th, 2024, the US Food and Drug Administration (FDA) granted accelerated approval to lisocabtagene maraleucel, a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, for adult patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least 2 prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor.

This regulatory decision was based on results from the phase 1/2 open-label, single-arm TRANSCEND CLL 004 study, the first pivotal multicenter trial to evaluate a CAR T-cell therapy in patients with relapsed or refractory CLL or SLL. The main outcome measures were response rate and duration of response.

The complete response (CR) rate associated with lisocabtagene maraleucel was 20% (95% confidence interval [CI], 11.1 to 31.8). Among the patient population that achieved a CR, the median duration of response was not reached (95% CI, 15 months to not reached [NR]) at the time of data cutoff. Among all responders (overall response rate [ORR], 45%; 95% CI, 32.3 to 57.5), the median duration of response was 35.3 months (95% CI, 12.4 to NR). Additionally, high rates of minimal residual disease (MRD) negative status were observed among patients treated with lisocabtagene maraleucel who achieved a CR, with an MRD-negativity rate of 100% in the blood (95% CI, 75.3 to 100) and 92.3% in the bone marrow (95% CI, 64 to 99.8). 

Occurrences of cytokine release syndrome (CRS) and neurologic events were mostly low grade among the study participants treated with lisocabtagene maraleucel. Furthermore, any grade of CRS occurred in 83% of patients, with grade 3 CRS occurring in 9% of patients. There were no grade 4/5 CRS events reported. Any grade neurologic events were reported in 46% of patients, with grade 3 NEs reported in 20% of patients and 1 case of grade 4 neurologic event. There were no grade 5 neurologic events reported.

Tanya Siddiqi, MD, lead study investigator and associate professor, City of Hope National Medical Center, Duarte, California, concluded, “The FDA approval of [lisocabtagene maraleucel] in relapsed or refractory CLL and SLL after treatment with a prior BTKi and BCL2i…shift[s] the treatment paradigm from continuous therapy with sequential regimens to overcome drug resistence, to a one-time personalized T-cell based approach that has the potential to offer patients complete and lasting remission.”

Source:

U.S. FDA approves Bristol Myers Squibb’s Breyanzi ® as the first and only CAR T cell therapy for adults with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Published online March 14, 2024. https://news.bms.com/news/corporate-financial/2024/U.S.-FDA-Approves-Bristol-Myers-Squibbs-Breyanzi--as-the-First-and-Only-CAR-T-Cell-Therapy-for-Adults-with-Relapsed-or-Refractory-Chronic-Lymphocytic-Leukemia-CLL-or-Small-Lymphocytic-Lymphoma-SLL/default.aspx