News from the FDA/CDC

FDA approves first CAR T-cell for adult ALL: For patients with R/R B-cell disease


 

The U.S. Food and Drug Administration has approved brexucabtagene autoleucel (Tecartus) for the treatment of adult patients (18 years and older) with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

The therapy is the first chimeric antigen receptor (CAR) T-cell treatment approved for adults with ALL.

This is a “meaningful advance,” because “roughly half of all adults with B-ALL will relapse on currently available therapies,” said Bijal Shah, MD, of Moffitt Cancer Center, Tampa, Fla., in a press statement from the manufacturer, Kite.

“A single infusion of Tecartus has demonstrated durable responses, suggesting the potential for long-term remission and a new approach to care,” he added.

“Roughly half of 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 at the Leukemia & Lymphoma Society, in the statement. The median overall survival (OS) is only about 8 months in this setting with current treatments, according to the company.

The new FDA approval, which is the fourth indication for brexucabtagene autoleucel, is based on results from ZUMA-3, a multicenter, single-arm study of 71 patients, with 54 efficacy-evaluable patients.

Efficacy was established on the basis of complete remission (CR) rate within 3 months after infusion and the duration of CR (DOCR). Twenty-eight (51.9%) of evaluable patients achieved CR, with a median follow-up for responders of 7.1 months. The median DOCR was not reached.

The median time to CR was 56 days. All 54 efficacy-evaluable patients had potential follow-up for 10 or more months with a median actual follow-up time of 12.3 months.

Among the 54 patients, the median time from leukapheresis to product delivery was 16 days and the median time from leukapheresis to infusion was 29 days.

Of the 17 study patients who did reach efficacy evaluation, 6 did not receive the agent because of manufacturing failure, 8 were not treated because of adverse events following leukapheresis, 2 underwent leukapheresis and received lymphodepleting chemotherapy but were not treated with the drug, and 1 treated patient was not evaluable for efficacy, per the prescribing information.

Among all patients treated with brexucabtagene autoleucel at its target dose, grade 3 or higher cytokine release syndrome (CRS) and neurologic events occurred in 26% and 35% of patients, respectively, and were generally well managed, according to the company.

The most common adverse reactions (≥20%) among ALL patients are fever, CRS, hypotension, encephalopathy, tachycardia, nausea, chills, headache, fatigue, febrile neutropenia, diarrhea, musculoskeletal pain, hypoxia, rash, edema, tremor, infection with pathogen unspecified, constipation, decreased appetite, and vomiting.

The prescribing information includes a boxed warning about the risks of CRS and neurologic toxicities; the drug is approved with a Risk Evaluation and Mitigation Strategy (REMS) because of these risks.

A version of this article first appeared on Medscape.com.

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