FDA Grants Priority Review to Liso-Cel in Relapsed/Refractory CLL/SLL


The FDA acceptance marks the first step in addressing the unmet need for a lasting treatment option for patients with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma.

The FDA has granted priority review to a supplemental biologics license application for lisocabtagene maraleucel (liso-cel; Breyanzi) as a treatment for adult patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) previously treated with a Bruton tyrosine kinase (BTK) inhibitor and a BCL2 inhibitor, according to a press release from Bristol Myers Squibb.1

Supporting data for the application came from the primary analysis of the phase 1/2 TRANSCEND CLL 004 study (NCT03331198). According to findings presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, the investigator-assessed complete response (CR)/CR with incomplete hematologic recovery (CRi) rate was 18% (95% CI, 11%-28%) among all patients who received liso-cel at a dose of 100x106 CAR-positive T cells (dose level 2; n = 87).2 The corresponding rate was 18% (95% CI, 9%-32%; P = .0006) in a subset of patients who experienced disease progression on BTK inhibitors or venetoclax (Venclexta; n = 49).

Data also highlighted an objective response rate (ORR) of 47% (95% CI, 36%-58%) per independent review committee assessment and an undetectable minimal residual disease (MRD) rate of 64% (95% CI, 53%-74%) in the entire study population. The corresponding rates in patients who had progressed on BTK inhibitors/venetoclax were 43% (95% CI, 29%-58%; P = .3931) and 63% (95% CI, 48%-77%). Patients included in the full study population also experienced a median time to first response of 1.5 months (range, 0.8-17.4) and a median time to first CR/CRi of 4.4 months (95% CI, 1.1-17.9).

Investigators reported that the most frequent grade 3 or higher treatment-emergent adverse effects (TEAEs) included neutropenia (61%), anemia (52%), and thrombocytopenia (41%). Other AEs of special interest were prolonged cytopenia (54%), grade 3 or higher infections (17%), and tumor lysis syndrome (11%).

“Currently, there is no standard of care for people living with relapsed or refractory CLL or SLL after treatment with BTK [inhibitor]- and BCL2 [inhibitor]-based regimens, leaving a critical unmet need for a treatment option that provides deep and lasting responses,” Anne Kerber, senior vice president and head of Late Clinical Development, Hematology, Oncology, Cell Therapy at Bristol Myers Squibb, said in the press release.1 “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.”

In the open-label, multi-center TRANSCEND CLL 004 study, all patients underwent lymphodepletion with fludarabine at 30 mg/m2 plus cyclophosphamide at 300 mg/m2 for 3 days prior to receiving liso-cel. Patients received liso-cel 2 to 7 days following lymphodepletion at 50x106 CAR-positive T cells (dose level 1) and dose level 2 in phase 1 and at dose level 2 in phase 2.

The trial’s primary end point was CR/CRi rate based on International Workshop on CLL 2018 criteria. ORR and undetectable MRD in blood were key secondary end points. Other secondary end points included duration of response, progression-free survival, overall survival, and safety.

Patients 18 years and older with relapsed/refractory CLL/SLL who experienced progression on or were ineligible for treatment with BTK inhibitors were able to enroll on the trial. Additional eligibility criteria included having an ECOG performance status of 0 or 1; adequate bone marrow, organ, and cardiac function; and no Richter transformation nor active central nervous system involvement.

This article originally appeared in CancerNetwork.

  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://shorturl.at/pJMS6
  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
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