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
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.”
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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®.
