FDA Alert

FDA Grants Accelerated Approval for First CAR-T Cell Treatment for Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

Anthony Calabro, MA

On March 14, the FDA granted accelerated approval to lisocabtagene maraleucel (liso-cel), a CD19-directed chimeric antigen receptor (CAR)-T cell therapy, for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least two prior lines of therapy, including Bruton tyrosine kinase (BTK) and B-cell lymphoma 2 (BCL-2) inhibitors.1,2

The FDA previously approved liso-cel as a second-line treatment option for adult patients with large B-cell lymphoma in June 2022.1

The accelerated approval was granted based on the results from the phase 1/2 open-label, single-arm, TRANSCEND CLL 004 study, which evaluated the safety and efficacy of liso-cel at the recommended phase 1 dosages in patients with relapsed or refractory CLL or SLL. Participants in the study received an intravenous infusion of liso-cel at one of two dose levels: 50 × 106 or 100 × 106.3 The main outcome measures of the study were complete response or remission.

“A single infusion of liso-cel was shown to induce complete response or remission (including with incomplete marrow recovery) in patients with relapsed or refractory CLL or SLL, including patients who had experienced disease progression on a previous BTK inhibitor and venetoclax failure,” the authors wrote in their study.3

The results showed that the complete response (CR) rate associated with liso-cel treatment was 20% (95% CI, 11.1% to 31.8%). Among those who achieved a CR, median duration of response was not reached (95% CI, 15 months to not reached [NR]) at the time of data cutoff. The overall response rate was 45% among all responders (95% CI, 32.3% to 57.5%) and median duration of response was 35.3 months (95% CI, 12.4 to NR).2

For patients treated with liso-cel who achieved a CR, high rates of minimal residual disease (MRD) negative status were observed. Indeed, the results showed a 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%).2

Low-grade occurrences of cytokine release syndrome (CRS) and neurologic events (NEs) were found among those treated with liso-cel. Any grade CRS occurred in 83% of patients, Grade 3 CRS occurred in 9% of patients, and no Grade 4/5 CRS events were reported. Any grade NEs were reported in 46% of patients, Grade 3 NEs occurred in 20% of patients, and one patient had a Grade 4 NE. No Grade 5 NEs were reported.2



  1. Fashoyin-Aje L. Supplemental Approval. US Food and Drug Administration. Published March 21, 2024. Accessed April 1, 2024.
  2. 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). News release. Bristol Myers Squibb; Published online March 14, 2024. Accessed March 27, 2024.
  3. Siddiqi T, Maloney DG, Kenderian SS, et al. Lisocabtagene maraleucel in chronic lymphocytic leukaemia and small lymphocytic lymphoma (TRANSCEND CLL 004): a multicentre, open-label, single-arm, phase 1-2 study. Lancet. 2023;402(10402):641-654. doi:10.1016/s0140-6736(23001052-8.