Follow-up Trial Results Reinforce Yescarta as Relapsed Non-Hodgkin’s Lymphoma Therapy

Follow-up Trial Results Reinforce Yescarta as Relapsed Non-Hodgkin’s Lymphoma Therapy

More than two years after receiving treatment with Yescarta (axicabtagene ciloleucel), 51% of non-Hodgkin’s lymphoma patients included in the ZUMA-1 Phase 1/2 clinical trial are still alive, and 39% are still responding to the CAR T-cell therapy, a follow-up analysis shows.

The findings continue to demonstrate the benefits of Kite Pharma‘s Yescarta in B-cell lymphoma patients who received at least two prior therapies — for whom it is approved in the U.S. and Europe — a population that lives only a median of 6.6 months with other available therapies.

The updated ZUMA-1 (NCT02348216) results were presented recently during the American Society of Hematology (ASH) 2018 Meeting, in San Diego, in a poster titled, “2-Year Follow-up and High-Risk Subset Analysis of Zuma-1, the Pivotal Study of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Refractory Large B Cell Lymphoma.” They were simultaneously published in The Lancet Oncology journal.

Like most CAR T-cell therapies, Yescarta uses a patient’s own immune T-cells, which are collected and genetically modified in a lab to produce a chimeric antigen receptor, or CAR. The receptor targets CD19, a protein found at the surface of most leukemia and lymphoma cells, priming T-cells to seek out and destroy these cells.

Yescarta was the second CAR T-cell product to be approved anywhere in the world, and is indicated in the U.S. since October 2017 for diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), high-grade B-cell lymphoma, and transformed follicular lymphoma.

The approval was based on ZUMA-1 results, which showed high response rates after a single infusion of Yescarta. Of the 101 patients treated with CAR T-cell product, 72% responded to therapy and 51% were in complete remission after a median follow-up of 7.9 months.

A recent analysis, conducted after a median of 27.1 months, shows that more patients responded to the treatment after the initial analysis, with 83% of patients experiencing a reduction in tumor burden, and 58% achieving a complete response.

Overall, responses lasted a median of 11.1 months, but at the time of the analysis 39% of patients — including 37% with complete response — had ongoing responses.

Patients in ZUMA-1 lived a median of 5.9 months without their disease worsening. However, 72% of patients who had achieved a complete response at three months lived past the two-year mark without signs of disease progression.

To date, more than half the patients are still alive, and researchers estimate the two-year overall survival at 50.5%.

Safety was largely similar to that of prior Yescarta reports, researchers said. All patients experienced some sort of adverse side effect, and most (98%) were severe or worse.

Cytokine release syndrome (CRS), a severe systemic immune reaction that causes high fever and flu-like symptoms and is often life-threatening, was experienced by 11% of patients in the study, but no new cases were reported since the one-year follow-up analysis. Yescarta also caused severe neurological events in one-third of participants.

Researchers also examined CAR T-cell persistence and B-cell recovery — because Yescarta also targets healthy B-cells — in patients with an ongoing response. At two years. 66% of patients still had CAR gene-marked cells, and 75% had measurable B-cells in their blood.

“This two-year assessment demonstrates that axi-cel [Yescarta] can induce durable remissions in a substantial proportion of patients with an acceptable long-term safety profile,” Sattva Neelapu, MD, said in a press release. Neelapu is professor of lymphoma and myeloma at The University of Texas MD Anderson Cancer Center, who co-led the study. “There also is evidence of gradual B-cell recovery in most patients with refractory large B-cell lymphoma who otherwise have limited treatment options.”

A subsequent assessment of patients who were treated with Yescarta at 17 academic centers across the U.S. showed that response rates in the “real-world” closely match those seen in ZUMA-1’s first analysis.

The study included 274 patients, half of whom would not be eligible to enter ZUMA-1. But after a median follow-up of four months, 81% of patients responded to Yescarta, and 58% had no traces of cancer.

The findings also were presented at the ASH 2018 Meeting, in a poster titled “Axicabtagene Ciloleucel (Axi-cel) CD19 Chimeric Antigen Receptor (CAR) T-Cell Therapy for Relapsed/Refractory Large B-Cell Lymphoma: Real World Experience.

“Although limited by a relatively short follow up, [four-month] responses in the real-world setting are comparable to the best responses observed in the pivotal ZUMA-1 clinical trial,” said senior author Loretta Nastoupil, MD, assistant professor of lymphoma and myeloma. “Importantly, safety appears comparable to the ZUMA-1 trial despite nearly half of patients failing to meet ZUMA-1 eligibility criteria.”

Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.

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