CAR T-cell Therapy Approved for Certain Blood Cancers
Lisocabtagene maraleucel was approved for some patients with advanced CLL or SLL.
The U.S. Food and Drug Administration (FDA) has granted accelerated approval to lisocabtagene maraleucel (Breyanzi) for the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in patients who have received at least two prior lines of therapy, including inhibitors of Bruton tyrosine kinase (BTK) and BCL-2.
Lisocabtagene maraleucel is a chimeric antigen receptor (CAR) T-cell therapy, a form of immunotherapy in which a patient’s own T cells (a type of immune cell) are extracted, genetically engineered in the lab to endow cancer-fighting ability, and then reinfused into the patient. Lisocabtagene maraleucel is designed to target the CD19 protein that is highly expressed by malignant B cells, including those that make up CLL and SLL.
Lisocabtagene maraleucel was previously approved for certain large B-cell lymphomas that relapsed or were refractory to other treatments.
The latest approval was based on results from TRANSCEND CLL 004, an open-label, multicenter, single-arm phase I/II clinical trial that enrolled adult patients with relapsed or refractory CLL or SLL who had been treated with at least two prior lines of therapy, including an inhibitor of BTK; many patients had also received an inhibitor of BCL-2.
Of 65 evaluable patients, 25% experienced partial responses, which endured for at least 12 months in 60.3% of patients and for at least 18 months in 46.9% of patients. Thirteen patients experienced a complete response, with a 12-month response rate of 100% and an 18-month response rate of 87.5%.
The recommended dosage for lisocabtagene maraleucel is 90×106 to 110×106 CAR-positive viable T cells, which should be administered intravenously for two to seven days after pretreatment with chemotherapy to deplete the patient’s existing immune cells.
The prescribing information for lisocabtagene maraleucel includes a boxed warning for life-threatening reactions, including cytokine release syndrome, neurologic toxicities, and secondary blood cancers.
CLL and SLL are blood cancers characterized by the overproduction of B cells, which are a type of immune cell. The location of the cancer cells determines whether the disease is CLL (cancer cells in the blood and bone marrow) or SLL (cancer cells in the lymph nodes and spleen). According to federal statistics, it was estimated that 20,700 individuals would be diagnosed with CLL and 4,440 patients would die of the disease in the United States in 2024.
The FDA rendered its decision on March 14, 2024. Accelerated approval means that continued approval may be contingent upon a confirmatory trial.
