FDA Approves Lisocabtagene Maraleucel For Treatment of Relapsed or Refractory CLL, SLL

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The approval was based on data from the phase 1/2 TRANSCEND CLL 004 study, in which the CAR T cell therapy demonstrated statistically significant complete response rates.

Lisocabtagene maraleucel (Breyanzi; liso-cel) has received accelerated approval from the FDA for the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in adult patients who have received at least 2 prior lines of therapy, Bristol Myers Squibb announced in a release.1

Lisocabtagene maraleucel demonstrated statistically significant complete response rates in a primary efficacy analysis / Postmodern Studio - stock.adobe.com

Lisocabtagene maraleucel demonstrated statistically significant complete response rates in a primary efficacy analysis / Postmodern Studio - stock.adobe.com

The approval was based on data from the phase 1/2 TRANSCEND CLL 004 (NCT03331198) study, in which lisocabtagene maraleucel demonstrated statistically significant complete response rates (CR) in a primary efficacy analysis, with no disease progression or deaths among the patients who achieved CR.

About TRANSCEND CLL 004

Trial Name: Study Evaluating Safety and Efficacy of JCAR017 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)

ClinicalTrials.gov Identifier: NCT03331198

Sponsor: Juno Therapeutics

Summary: This is a Phase 1/2, open-label, multicenter study to determine the efficacy and safety of JCAR017 in adult subjects with relapsed or refractory CLL or SLL. The study will include a Phase 1 part to determine the recommended dose of JCAR017 monotherapy in subjects with relapsed or refractory CLL or SLL, followed by a Phase 2 part to further assess the efficacy and safety of JCAR017 monotherapy treatment at the recommended dose. A separate Phase 1 cohort will assess the combination of JCAR017 and concurrent ibrutinib. Another separate Phase 1 cohort will assess the combination of JCAR017 and concurrent venetoclax. In all subjects, the safety, efficacy, and pharmacokinetics (PK) of JCAR017 will be evaluated.

“CAR T cell therapies represent a transformative treatment option for patients with certain types of blood cancers,” Bryan Campbell, senior vice president and head of Commercial of Cell Therapy at Bristol Myers Squibb, said in a release.1 “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.”

TRANSCEND CLL 004 in an open-label, single-arm, phase 1/2 study evaluating lisocabtagene maraleucel in adult patients with relapsed or refractory CLL or SLL. The study included 117 adult participants who underwent leukapheresis between January 2018 and June 2022 at 27 sites in the United States. All participants had previously received treatment with Bruton’s tyrosine kinase (BTK) inhibitors that failed, with a median of 5 previous lines of therapy.

READ MORE: FDA Grants Accelerated Approval to Zanubrutinib for R/R Follicular Lymphoma

Of the participants, the median age was 65 years, 32% were female, 68% were male, 85% were White, 4% were Black or African American, 2% were other races, and 11% were unknown race. All participants received a single intravenous infusion of lisocabtagene maraleucel at 1 of 2 dose levels: 50×106 or 100×106 chimeric antigen receptor-positive T cells.

For the primary efficacy analysis, the study found that, of 49 patients who received the 100×106dose, the rate of CR or remission was 18%. Among patients who responded to treatment, the median duration of response was 35.3 months. There was an observed minimal residual disease negative status of 100% in the blood and 92.3% in the bone marrow. Of patients treated with lisocabtagene maraleucel, 9% experienced grade 3 cytokine release syndrome and 18% experienced grade 3 neurological events. There were 51 deaths in the study, with 43 occurring after infusion with lisocabtagene maraleucel.2

“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 in the Division of Lymphoma at the City of Hope National Medical Center, said in a release.1 “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.”

Due to the accelerated approval given by the FDA, continued approval of lisocabtagene maraleucel for the current indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

READ MORE: Oncology Resource Center

References
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 15, 2024. https://news.bms.com/news/corporate-financial/2024/U.S.-FDA-Approves-Bristol-Myers-Squibbs-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/default.aspx
2. 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(23)01052-8
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