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FDA approves lisocabtagene maraleucel for R/R CLL or SLL

On March 14th, 2024, the U.S. Food and Drug Administration (FDA) granted accelerated approval to lisocabtagene maraleucel (liso-cel) for adult patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.1

Liso-cel is an autologous, CD19-directed CAR-T cell product with a 4-1BB costimulatory domain, and its approval is based on data from the Phase I/II TRANSCEND-CLL-004 trial (NCT03331198). Among 89 patients treated with liso-cel in this trial, a complete response (CR) rate of 20% (95% CI: 11.1-31.8) was observed. At the time of data cut-off, the median duration of response (DOR) was not yet reached in those who achieved a CR (95% CI: 15 months-NR), and high rates of measurable residual disease (MRD) negativity were observed across these patients.1, 2  

At the 2023 ASH Annual Meeting and Exposition, Tanya Siddiqi, MD, City of Hope, Duarte, CA, shared an update from the TRANSCEND-CLL-004 trial, stating that, “the bottom line is, it’s one treatment of CAR-T cells, and now people are going two/three years without relapsing, which gives them a lot of clinical benefit where they don’t have to be continuously on pills, suffer side effects, frequent doctors’ visits, and things like that.”

Regarding safety, liso-cel includes a warning for cytokine release syndrome (CRS), neurologic toxicities, and secondary hematological malignancies. In this trial, rates of CRS were mostly low grade, with grade 3 CRS occurring in only 9% of patients, and no reports of grade 4 or 5 CRS. Neurologic events (NEs) were reported in 46% of patients, with grade 3 NEs reported in 20% of patients, and only one case of grade 4 NE reported.1

Liso-cel is the first CAR-T cell therapy approved for this indication, and it is hoped to provide a promising new therapeutic option for patients with a critical medical need.

References

  1. Bristol Myers Squibb. 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). Available here. (Last accessed 15/03/2024).
  2. Kharfan-Dabaja MA, Yassine F, Moustafa MA, et al. Lisocabtagene Maraleucel in Relapsed or Refractory Diffuse Large B Cell Lymphoma: What is the Evidence? Hematology/Oncology Stem Cell Therapy. 2022 Dec 23;15(4):168-175.

Written by Anya Dragojlovic Kerkache

Edited by Thomas Southgate