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Heavily pretreated adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (B-ALL) achieved a high and durable response rate with the CAR T-cell therapy brexucabtagene autoleucel (Tecartus), according to results from the .

At a median follow-up of 16.4 months, 71% of patients achieved a complete response (CR) or CR with incomplete hematological recovery (CRi), with a majority of the responses associated with undetectable minimal residual disease (MRD), reported Bijal Shah, MD, of the Moffit Cancer Center in Tampa, Florida.

The efficacy and manageable safety profile, "support the promising role of [brexucabtagene autoleucel] to provide long-term clinical benefit in adult patients with relapsed B-cell ALL," said Shah, during a presentation at the American Society of Clinical Oncology virtual meeting. Results of ZUMA-3 were published simultaneously in the .

According to a release from Kite, the agent's manufacturer, the FDA has granted for its use in the treatment of adult patients with relapsed or refractory B-cell precursor ALL.

Shah noted that approximately 40%-50% of adults with B-ALL experience a relapse after treatment, and subsequently have an overall poor prognosis. The 1-year overall survival (OS) rate for patients with relapsed/refractory B-ALL is just 26% after first salvage, and decreases with additional lines of therapy.

The autologous anti-CD19 CAR T-cell therapy brexucabtagene autoleucel received last year for relapsed/refractory mantle cell lymphoma. ZUMA-3 is designed to evaluate the drug in adults in the refractory/relapsed B-ALL setting.

In phase I of the trial, brexucabtagene autoleucel achieved an overall CR/CRi of 83%, with a manageable safety profile, and at a recommended dose established as 1x10⁶ CAR T cells/kg.

In phase II of the study, 71 patients with relapsed/refractory disease were enrolled. Of the 55 patients treated with brexucabtagene autoleucel, 47% had been heavily pretreated (three or more previous therapies).

"The primary endpoint was met, with a CR/CRi rate of 70.9%, including a true CR rate of 56.4%," Shah reported.

In addition, results from the study showed that the MRD negativity rate was 97% among responders and that the median time to CR/CRi was 1.1 month. Ten patients went on to allogeneic stem cell transplantation, including 9 with CR/CRi.

"Responses were largely consistent among subgroups, including those who were older, those who were more heavily pretreated, and those with prior allogeneic transplant, blinatumomab, inotuzumab, and those were considered primary refractory," Shah pointed out, adding that the only group to show a lower response rate were those with a bone marrow blast burden of >75%.

Median OS in the study population was 18.2 months, and not reached among responders. Median relapse-free survival was 11.6 months, and 14.2 months among responders.

"Toxicity was largely consistent with our phase I experience," Shah said, with the most common grade ≥3 adverse events (AEs) of anemia or fever. Grade ≥3 cytokine release syndrome and neurologic AEs occurred in 24% and 25% of patients, respectively, and were generally reversed with treatment. Ten grade 5 events were reported, two of which were related to brexucabtagene autoleucel.

"Longer-term data will be required to determine whether [brexucabtagene autoleucel] therapy will induce long-term durable responses frequently enough to consider it definitive therapy," wrote Marcela Maus, MD, PhD, of Massachusetts General Hospital in Boston, in an accompanying . "But it seems to have a clear place in the management of relapsed or refractory acute lymphoblastic leukemia in adults."