FDA Approves Liso-Cel (Breyanzi) as First CAR-T for CLL, SLL


Breyanzi was approved for the expanded indication under the accelerated approval pathway.

Tanya Siddiqi, MD

Tanya Siddiqi, MD

The FDA has approved Bristol Myers Squibb’s chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel (liso-cel; Breyanzi) for treating adults with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least 2 prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor, under the accelerated approval pathway.

The approval marks the first CAR T-cell therapy approved for treating CLL or SLL. Breyanzi was previously approved for the second-line treatment of relapsed or refractory large B-cell lymphoma (LBCL) in the US, Japan, and Europe, and for relapsed and refractory LBCL after 2 or more lines of systemic therapy in Japan, Europe, Switzerland, and Canada.

Liso-cel is an autologous CD19-directed CAR T cell therapy with a 4-1BB costimulatory domain designed to enhance the expansion and persistence of the CAR T cells. It will be delivered to patients with CLL or SLL in a one-time infusion with a single dose containing 90 to 110 x 106 CAR-positive viable T cells.

“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, associate professor, Division of Lymphoma, City of Hope National Medical Center, said in a statement.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.”

WATCH NOW: Brian Koffman, MDCM, on Keeping Pace in Chronic Lymphocytic Leukemia Research

Siddiqi served as primary investigator on the TRANSCEND CLL004 study (NCT03331198), which was the first pivotal multicenter trial to evaluate a CAR T cell therapy in patients with relapsed or refractory CLL or SLL. Siddiqi presented the latest data from TRANSCEND CLL004 at the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition, held December 9-12, in San Diego, California.2

In 118 patients with CLL or SLL, the complete response (CR) rate with incomplete marrow recovery (CRi) rate was 20% (95% CI, 10.0-33.7) at dose level 2, with an overall response rate (ORR) of 44% (95% CI, 30.0-58.7). Eight of 9 patients with a best overall response of CR/CRi had ongoing responses as of the last assessment.2

In the safety dataset, cytokine release syndrome (CRS) was reported among 85% of patients (grade 3, 8%) and the rate of neurological events (NEs) was 45% (grade 3, 18%; grade 4, 1%).2

Other adverse events (AE) included prolonged cytopenia (54%), infections of grade 3 or higher (18%), hypogammaglobulinemia (15%), tumor lysis syndrome (11%), second primary malignancy (9%), and macrophage activation syndrome (3%). Overall, 33% (n = 45) of the 137 leukapheresed patients died after liso-cel infusion (disease progression, 20%; AE, 4%; other reasons, 9%).2

The new approval stands to transform the treatment landscape of CLL and SLL, which had previously laid stagnant.

“Many clinicians, and even more people in pharmaceutical industry see CLL as a solved problem. And we are blessed to have incredible therapies, as a patient myself, I can say that I would not be alive today if not for these breakthrough therapies and the clinical trials that I've been in. But CLL is not a solved problem, it's more like 2 strikes and you're out,” Brian Koffman, MDCM, DCFP, FCFP, DABFP, MSEd, cofounder of CLL Society, previously told CGTLive®.

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. 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 (liso-cel) in R/R CLL/SLL: 24-Month Median Follow-up of TRANSCEND CLL 004. Presented at: 2023 ASH Annual Meeting & Exposition, December 9-12; San Diego, California. Abstract 330
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