FDA Approves Liso-Cel for Relapsed/Refractory CLL/SLL


Patients with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma can now receive lisocabtagene maraleucel after the FDA approved the drug, which was based on the phase 1/2 TRANSCEND CLL trial.


The FDA has approved lisocabtagene maraleucel (liso-cel; Breyanzi) as a treatment for adult patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least 2 prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.1

The approval is based on the data from the phase 1/2 TRANSCEND CLL 004 trial (NCT03331198), which assessed complete responses (CR) and CRs with incomplete hematologic recovery (CRi). Results showed that the CR rate associated with liso-cel was 20% (95% CI, 11.1-31.8), and the median duration of response (DOR) of those who achieved a CR was not reached (95% CI, 15 months-not reached [NR]) at the data cutoff.

The overall response rate was 45% (95% CI, 32.3-57.5), and the overall median DOR was 35.3 months (95% CI, 12.4-NR). The minimal residual disease (MRD)–negativity rate was 100% in the blood (95% CI, 75.3-100) and 92.3% in the bone marrow (95% CI, 64-99.8).

“CLL and SLL are currently considered incurable diseases with few treatment options in the relapsed setting that can confer complete responses, something that has historically been associated with improved long-term outcomes,” Tanya Siddiqi, MD, lead investigator and associate professor, Division of Lymphoma, City of Hope National Medical Center, stated in the news release. “The FDA approval of liso-cel in relapsed or refractory CLL and SLL after treatment with prior BTKi and BCL2i is a remarkable breakthrough, shifting the treatment paradigm from continuous therapy with sequential regimens to overcome drug resistance, to a one-time personalized T-cell based approach that has the potential to offer patients complete and lasting remission.”

This open-label, single-arm study included patients 18 or older with high-risk or standard-risk relapsed/refractory CLL or SLL and at least 2 previous lines of therapy, including a BTK inhibitor. Patients first underwent lymphodepletion, which consisted of 30 mg/m2 of fludarabine and 300 mg/m2 of cyclophosphamide for 3 days, and then received either 50 x 106 chimeric antigen receptor (CAR)+ T cells in dose level 1 and 100 x 106 CAR+ T cells in dose level 2.

A total of 137 patients underwent leukapheresis, 117 received liso-cel, and 96 were evaluable for efficacy; 87 patients were treated at dose level 2. In the subset of patients that were pretreated with a BTK inhibitor or venetoclax (Venclexta), 82 underwent leukapheresis, 70 received liso-cel, and 53 were evaluable for efficacy; 49 patients received liso-cel at dose level 2.

The median age of the patients was 65.0 years (range, 49-82), and patients received a median of 5 prior lines of systemic therapy (range, 2-12).

To be eligible for enrollment, patients needed to have an ECOG performance status of 0 or 1 and adequate bone marrow, organ, and cardiac function. Patients who experienced disease progression or who were not eligible for treatment with BTK inhibitors were eligible to enroll on the study.

Findings presented at the 2023 ASCO Annual Meeting showed that, at a median follow-up of 21.0 months (95% CI, 17.5-26.6), the CR/CRi rate was 18% (95% CI, 11%-28%) among all patients who received liso-cel at dose level 2 (n = 87).2,3 The corresponding rate was 18% (95% CI, 9%-32%; P = .0006) in the subset of patients who experienced disease progression on BTK inhibitors or venetoclax (Venclexta; n = 49).

Findings also showed that liso-cel resulted in an objective response rate (ORR) of 47.1% (95% CI, 36.3%-58.1%) and an undetectable minimal residual disease (MRD) rate of 64.4% (95% CI, 53.4%-74.4%) in the overall patient population. In the subset that progressed on BTK inhibitors or venetoclax, the ORR was 43% (95% CI, 29%-58%; P = .3931), and the MRD rate was 63% (95% CI, 48%-77%).

Median progression-free survival (PFS) was 18.0 months (range, 9.4-30.1) for patients at dose level 2, and median overall survival (OS) was 30.3 months (11.2-NR). In the subset of patients who progressed on BTK inhibitors or venetoclax, the median PFS was 11.9 (5.7-26.2), and the median OS was 30.3 months (11.2-NR).

Regarding safety, the most common adverse effects (AE) that were grade 3 or higher were neutropenia (61%), anemia (52%), and thrombocytopenia (41%). Cytokine release syndrome (CRS) occurred in 83% of patients; 9% of these cases were grade 3, and no grade 4 or 5 instances of CRS were recorded.1

All-grade and grade 3 neurologic toxicities were reported in 46% and 20% of patients; 1 case of grade 4 neurotoxicity was reported.1

A total of 51 deaths occurred during the study, 8 of which occurred before CAR T-cell infusion and 43 of which occurred after. Three and 27 of these deaths were due to disease progression. Of the 16 deaths that occurred without progression after CAR T-cell infusion, 5 were due to AEs, 4 of which were found to be unrelated to treatment with liso-cel.

“CAR T cell therapies represent a transformative treatment option for patients with certain types of blood cancers,” Bryan Campbell, senior vice president, Head of Commercial, Cell Therapy, Bristol Myers Squibb, the developer of liso-cel, stated in the release. “For years, attempts to bring other CAR T cell therapies to patients with relapsed or refractory CLL or SLL met challenges and found little success. With the approval of Breyanzi as the first CAR T for relapsed or refractory CLL or SLL, we are now able to offer these patients a personalized option, while further expanding access across the broadest array of B-cell malignancies, to address this critical unmet need.”


  1. 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. March 14, 2024. Accessed March 14, 2024. https://www.businesswire.com/news/home/20240313169337/en/U.S.-FDA-Approves-Bristol-Myers-Squibb
  2. Siddiqi T, Maloney DG, Kenderian SS, et al. Lisocabtagene maraleucel (liso-cel) in R/R chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): Primary analysis of TRANSCEND CLL 004. J Clin Oncol. 41(suppl 16; abstr 7501). doi:10.1200/JCO.2023.41.16_suppl.7501
  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. The Lancet. Published online June 6, 2023. doi:10.1016/S0140-6736(23)01052-8

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