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Neelapu Hopeful FDA Will Approve Axicabtagene Ciloleucel for NHL

Danielle Bucco
Published: Monday, May 08, 2017

Sattva S. Neelapu, MD

Sattva S. Neelapu, MD

Last month, a biologics license application (BLA) was submitted to the FDA for the CAR T-cell therapy axicabtagene ciloleucel (axi-cel; KTE-C19) as a potential treatment for transplant ineligible patients with relapsed or refractory aggressive non-Hodgkin lymphoma (NHL)

The BLA was based on findings from the phase II ZUMA-1 study, in which axi-cel demonstrated an objective response rate (ORR) of 82% and a complete response (CR) rate of 54% for patients with NHL.

“We are hoping that this [data] will lead to an FDA approval of this product. This is the first anti-CD19 CAR T-cell therapy trial that has shown significant clinical benefits in patients with chemotherapy refractory aggressive B-cell NHL,” said Sattva S. Neelapu, MD, an author on the ZUMA-1 trial.

In an interview with OncLive at the 2017 AACR Annual Meeting, Neelapu, associate professor, The University of Texas MD Anderson Cancer Center, discussed the ZUMA-1 trial and the potential impact of these results on patients with non-Hodgkin lymphoma.

OncLive: Can you provide some background on the objectives ZUMA-1?

Neelapu: ZUMA-1 is the first multicenter trial of anti-CD19 CAR T-cell therapy—specifically axicabtagene ciloleucel, also known as axi-cel or KTE-C19—in patients with refractory aggressive B-cell NHL.

To be eligible for this trial, patients had to have either diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma, or transformed follicular lymphoma. They also had to have chemotherapy refractory disease, which is defined as stable disease or progressive disease to the last line of therapy or relapsed within 12 months after prior autotransplant.

The primary objective for the trial was ORR.

How was the trial designed?

This single-arm study had 2 cohorts. Cohort 1 included patients with DLBCL. Cohort 2 included patients with primary mediastinal B-cell lymphoma and transformed follicular lymphoma.

Following enrollment, the patients underwent leukapheresis and once the product had been manufactured, they resumed conditioning chemotherapy with cyclophosphamide and fludarabine for 3 days. Two days later, patients received an autologous CD19 CAR T-cell therapy particle, axi-cel, at a dose of 2 million cells/kg of body weight.

What were the significant findings from this study?

We enrolled a total of 101 patients at 22 different sites. Of these 101 patients in the primary analysis, we discovered the best ORR was 82% and the CR rate was 54%. The study met its primary endpoint at this analysis with a P value of less than .0001.

At the median follow-up of 8.7 months, 44% of patients had ongoing responses and 39% had ongoing complete remissions. This compares very favorably to historical data where in a similar refractory population, the ORR with existing therapy is 26% and the CR rate is only 8%. The median survival for these patients with the current therapies is 6 and a half months. This study had a median follow-up of 8.7 months, with the majority of the patients still alive. In fact, at just 6 months, 80% of the patients were still alive.

What were the toxicities associated with this treatment?

There are 2 toxicities observed with axi-cel. In this particular study, it was determined that 13% of the patients had cytokine release syndrome of grade 3 or higher and 28% of the patients had neurological toxicities of grade 3 or higher. The cytokine release syndrome is usually manifested as a fever, or perhaps hypertension or hypoxia. However, the majority of the side effects were reversible.

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Oncology Consultations®: The Advancing Role of CAR T-Cell Therapies in Hematologic MalignanciesApr 30, 20191.5
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