FDA Accepts sBLA for Liso-Cel in Relapsed or Refractory CLL/SLL


The application for lisocabtagene maraleucel in relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma has been accepted by the FDA, following positive results from the TRANSCEND CLL 004 study.

  • TRANSCEND CLL 004 (NCT03331198) is the first pivotal, multicenter, trial to show clinical benefit with a CD19-directed chimeric antigen receptor (CAR) T-cell therapy in this patient population.

  • Regardless of prior progression on Bruton’s tyrosine kinase (BTK) inhibition or absence of clinical benefit with venetoclax (Venclexta), lisocabtagene maraleucel (liso-cel; Breyanzi) demonstrated durable responses in the phase 1/2 study.

  • The FDA has set a Prescription Drug User Fee Act (PDUFA) date of March 14, 2024.

The FDA has accepted the supplemental biologics license application (sBLA) for liso-cel to expand its current indication to include the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who received a prior BTK inhibitor (BTKi) and B-cell lymphoma 2 inhibitor (BCL2i).1

Findings from the primary analysis of the phase 1/2 TRANSCEND CLL 004 study support this regulatory decision as liso-cel demonstrated encouraging responses among patients with relapsed/refractory CLL/SLL.2 At a median follow-up of 21.0 months (95% CI, 17.5-26.6), the complete response (CR) rate/CR with incomplete hematologic recovery (CRi) rate as assessed by independent review committee (IRC) was 18% (95% CI, 11%-28%) in the 87 patients given liso-cel at dose level 2.

In this group, the IRC-assessed objective response rate (ORR) was 47% (95% CI, 36%-58%), and the rate of undetectable minimal residual disease (uMRD) in the blood was 64% (95% CI, 53%-74%).

“This FDA acceptance brings us one step closer to offering these patients, for the first time, a personalized, T-cell-based treatment option. We’re proud to further our commitment to bring the potential of CAR T-cell therapy to more patients, building on [liso-cel’s] foundation as a differentiated treatment option that has shown clinical benefit in the broadest array of B-cell malignancies,” said Anne Kerber, senior vice president and head, late clinical development, hematology, oncology, cell therapy, Bristol Myers Squibb, in a press release.1

Red blood cells: © vipman4 - stock.adobe.com

Red blood cells: © vipman4 - stock.adobe.com

In additional findings from this population, the uMRD rate in marrow was 59% (95% CI, 48%-69%), the best overall response included CR/CRis (18%), partial responses (PR)/non-confirmed PR (29%), stable disease (39%), and progressive disease (7%).2 Further, 6 patients (7%) were not evaluable. In the full study population, the median time to first response was 1.5 months (range, 0.8-17.4) and the median time to first CR/CRi was 4.4 months (range, 1.1-17.9), according to findings presented at the 2023 ASCO Annual Meeting.

With these data, the FDA has granted the application priority review and set a PDUFA goal date of March 14, 2024.1

“Currently, there is no standard of care for people living with relapsed or refractory CLL or SLL after treatment with BTKi- and BCL2i-based regimens, leaving a critical unmet need for a treatment option that provides deep and lasting responses,” explained Kerber.

TRANSCEND CLL 004 is an open-label, multicenter study evaluating liso-cel for the treatment of patients with relapsed or refractory CLL or SLL. In the phase 1 dose-escalation portion of the study, the safety and recommended dose of liso-cel to be studied in phase 2 were evaluated. In the subsequent phase 2 expansion portion, liso-cel is being examined at the recommended dose as determined from the phase 1 monotherapy arm. The primary end point in phase 2 portion was CR rate, including CRi with bone marrow recovery.

Patients at least 18 years of age and older with relapsed/refractory CLL/SLL who had previously progressed on or were ineligible for BTK inhibition were eligible for inclusion in the study.3 The trial required patients to be at high or standard risk. This was defined by absence of efficacy with at least 2 or at least 3 prior lines of treatment, respectively. Additionally, patients were required to have an ECOG performance status of 0 or 1, adequate bone marrow, organ, and cardiac function, and absence of Richter transformation and active central nervous system involvement by malignancy.

This pivotal, multicenter, phase 1/2 study is the first to demonstrate a clinical benefit with a CD19-directed CAR T-cell therapy in patients with relapsed or refractory CLL after progression following treatment with a BTKi and BCL2i.1 If granted approval by the FDA, liso-cel would be the first CAR T-cell therapy available for this patient population.

  1. U.S. food and drug administration accepts for priority review Bristol Myers Squibb’s application for breyanzi (lisocabtagene maraleucel) for relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). News release. Bristol Myers Squibb. November 9, 2023. Accessed November 9, 2023. https://tinyurl.com/434347ka
  2. Siddiqi T, Maloney DG, Kenderian S, 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. 2023;41(suppl 16):7501. doi:10.1200/JCO.2023.41.16_suppl.7501
  3. Study evaluating safety and efficacy of JCAR017 in subjects with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). ClinicalTrials.gov. Updated August 29, 2023. Accessed November 9, 2023. https://clinicaltrials.gov/study/NCT03331198
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