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.”

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