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CAR-T Brexucabtagene Autoleucel Induces Long-Term Response in Patients with MCL

CAR-T

Long-term follow-up data from the ZUMA-2 trial found that brexucabtagene autoleucel resulted in an objective response rate (ORR) of 91% (95% CI, 81.8-96.7) in patients with relapsed/refractory mantle cell lymphoma (MCL). The results were presented at the 2022 ASCO Annual Meeting.

Brexucabtagene autoleucel is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy that is approved for the treatment of patients with relapsed/refractory MCL. Earlier data from the pivotal, single-arm, multicenter, phase II ZUMA-2 trial observed a 93% ORR, including a 67% complete response (CR) rate, after a median of 12.3 months of follow-up in 60 evaluable patients.

The study included adult patients with relapsed/refractory MCL who received one to five prior regimens, including anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 monoclonal antibody, and a Bruton’s tyrosine kinase inhibitor. Patients (n=68) underwent leukapheresis and conditioning chemotherapy, followed by a single infusion of brexucabtagene autoleucel.

As of July 24, 2021 (data cutoff), following a median follow-up of 35.6 months (range, 25.9-56.3 months), the updated ZUMA-2 trial results revealed a 68% CR rate (n=46; 95% CI, 55.2-78.5) and a median duration of response (DOR) of 28.2 months (95% CI, 13.5-47.1) among responders. More than a third of patients had ongoing response at data cutoff.

Median progression-free survival (PFS) and overall survival (OS) were 25.8 months (95% CI, 9.6-47.6) and 46.6 months (95% CI, 24.9-not estimable), respectively. Three patients experienced late relapse (defined as more than 24 months post-infusion).

Twenty-nine patients were evaluable for minimal residual disease (MRD); 24 were MRD-negative at month one, and 15 of 19 evaluable patients remained MRD-negative at month six.

Among the 15 MRD-negative patients at six months, median DOR, PFS, and OS were all not reached, and the ORR was 100%. Comparatively, among four MRD-positive patients, median DOR, PFS, and OS were 6.1 months, 7.1 months, and 27.0 months, respectively.

MRD-negative status at months one, three, and six was associated with durable response, with 55%, 71%, and 69%, respectively, of MRD-negative patients remaining in ongoing CR at data cutoff. The study found that circulating tumor DNA analysis of MRD at months three and six was predictive of relapse.

The most common grade ≥3 adverse events was neutropenia; seven events (10%) were grade 4. Two patients had treatment-related grade 3 serious infections, including pneumonia, upper respiratory tract infection, and influenza. During follow-up, no new cases of cytokine release syndrome occurred; one new serious grade 3 case of encephalopathy (13.0 months post-infusion) occurred, which was not considered related to study treatment, according to the authors.

Three new grade 5 adverse events occurred, none of which were considered related to study treatment: Salmonella bacteremia (24.9 months post-infusion), myelodysplastic syndromes (25.2 months post-infusion), and acute myeloid leukemia (37.5 months post-infusion).

“Collectively, these findings confirm the durable benefits of [brexucabtagene autoleucel] and support future investigations of CD19-directed CAR T-cell therapy in patients with high-risk MCL in earlier treatment lines,” the authors concluded.

The study was funded by Kite Pharma.

Reference

Wang M, Munoz J, Goy A, et al. Three-year follow-up of outcomes with KTE-X19 in patients with relapsed/refractory mantle cell lymphoma in ZUMA-2. Abstract #7518. Presented at the 2022 American Society of Clinical Oncology Annual Meeting, June 3-7, 2022.

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