FDA OKs First CAR T-Cell Therapy for Adult ALL

The FDA approved brexucabtagene autoleucel (Tecartus) late on Friday for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

Approval of brexucabtagene autoleucel represents the first chimeric antigen receptor (CAR) T-cell therapy for an adult ALL population, and was based on results from the single-arm multicenter ZUMA-3 study.

“Adults with ALL face a significantly poorer prognosis compared to children, and roughly half of all adults with B-ALL will relapse on currently available therapies,” said investigator Bijal Shah, MD, of the Moffitt Cancer Center in Tampa, Florida, in a press release from manufacturer Kite Pharma. “We now have a new meaningful advancement in treatment for these patients. A single infusion of Tecartus has demonstrated durable responses, suggesting the potential for long-term remission and a new approach to care.”

Patients in ZUMA-3 received a single infusion of the CD19-directed product following completion of lymphodepleting chemotherapy. The outcome measures that led to the approval were complete response (CR) achieved within 3 months from infusion and duration of CR. Of 54 evaluable patients, 52% achieved a CR within 3 months. With a median follow-up of 7.1 months for responders, the median duration of CR was not reached, and was estimated to exceed 12 months for more than half of patients.

“Roughly half of all ALL cases actually occur in adults, and unlike pediatric ALL, adult ALL has historically had a poor prognosis,” said Lee Greenberger, PhD, chief scientific officer of the Leukemia & Lymphoma Society (LLS), in the press release. “Developing new therapies that would be life-changing for people with cancer has been a dream of LLS. We are proud to see the potential of CAR T realized for even more people with this approval for brexucabtagene autoleucel.”

Prescribing information for the drug includes a boxed warning for the risks of cytokine release syndrome (CRS) and neurologic toxicities.

ZUMA-3 investigators found that CRS occurred in 92% (grade ≥3 in 26%) of patients, and neurologic toxicities occurred in 87% (grade ≥3 in 35%).

The most common non-laboratory adverse reactions included fever, CRS, hypotension, encephalopathy, tachycardias, nausea, chills, headache, fatigue, febrile neutropenia, diarrhea, musculoskeletal pain, hypoxia, rash, edema, tremor, infection with an unspecified pathogen, constipation, decreased appetite, and vomiting.

Brexucabtagene autoleucel is also approved for mantle cell lymphoma.