Chronic lymphocytic leukemia and small lymphocytic lymphoma are considered incurable, and patients whose disease has outlasted the standard drugs have had few options. On March 14, 2024 the US Food and Drug Administration gave accelerated approval to lisocabtagene maraleucel, sold as Breyanzi, a CD19-directed CAR T-cell therapy made by Bristol Myers Squibb.
It is cleared for adults whose CLL or SLL has returned or stopped responding after two or more earlier regimens, among them a Bruton tyrosine kinase inhibitor and a BCL2 inhibitor. HealthDay described it as the first CAR T product for these patients.
What the trial found
The approval rests on TRANSCEND CLL 004, a phase 1/2 open-label, single-arm study. It was the first pivotal multicenter study to test a CAR T product against these relapsed or refractory cancers. Among 89 patients treated, the complete response rate was 20%. The overall response rate was 45%, and responders held their response for a median of 35.3 months.
For people who reached a complete response, the median had not been reached when the data were cut off. Tests for minimal residual disease came back undetectable in 100% of those patients’ blood and 92.3% of their bone marrow.
Tanya Siddiqi of City of Hope National Medical Center, the lead investigator, called the approval “a remarkable breakthrough.” She said it moves treatment away from continuous drugs given one regimen after another and toward a single personalized T-cell approach that could bring complete, lasting remission.
How it is given, and the risks
Treatment ends in one infusion of 90 to 110 x 106 viable T cells carrying the CAR. The label carries boxed warnings for cytokine release syndrome, neurologic toxicities and secondary hematologic malignancies.
Side effects in the trial were mostly low-grade. Any-grade cytokine release syndrome hit 83% of patients; grade 3 hit 9%, and no grade 4 or 5 events. Neurologic events of any grade appeared in 46% of patients, grade 3 in 20%, with one grade 4 case and no grade 5.
The approval is conditional. Keeping the indication may hinge on confirmatory trials that verify clinical benefit.
Sources
- Accelerated Approval Granted to First CAR T-Cell Therapy for Relapsed or Refractory CLL/SLL (The ASCO Post)
- FDA Approves First CAR T-Cell Therapy for Adults With Leukemia or Lymphoma (HealthDay)
