FDA Approves Kite’s Yescarta for Relapsed or Refractory Follicular Lymphoma as Third Line Therapy

Rare Daily Staff

The U.S. Food and Drug Administration granted accelerated approval to Gilead Sciences subsidiary Kite’s Yescarta for the treatment of adult patients with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy.

The approval makes Yescarta the first chimeric antigen receptor (CAR) T-cell therapy approved for patients with indolent follicular lymphoma, follows FDA Breakthrough Therapy Designation and a priority review, and marks the third approved indication for a Kite cell therapy.

Follicular lymphoma (FL) is a form of indolent non-Hodgkin lymphoma (iNHL) in which malignant tumors slowly grow but can become more aggressive over time. Although a rare cancer, FL is the most common form of indolent lymphoma and the second most common type of lymphoma globally. It accounts for approximately 22 percent of all lymphomas diagnosed worldwide. Currently, there are limited options for the treatment of relapsed or refractory indolent FL after two or more lines of therapy.

The approval is based on results from ZUMA-5, a single-arm, open-label study in which 91 percent of patients with relapsed or refractory FL responded to Yescarta, including an estimated 74 percent of patients in a continued remission at 18 months (Kaplan-Meier estimate). Among all FL patients, median duration of response was not reached at a median follow-up of 14.5 months. In the safety analysis set, Grade 3 or higher cytokine release syndrome (CRS) and neurologic toxicities occurred in 8 percent and 21 percent of patients, respectively.

“Once a follicular lymphoma patient’s disease relapses, the duration of response to care shortens with each round of therapy,” said Caron Jacobson, medical director, Immune Effector Cell Therapy Program, Dana-Farber Cancer Institute and assistant professor of medicine, Harvard Medical School. “Additionally, for follicular patients in the third line of therapy, the five-year survival rate is only 20 percent, highlighting the urgent need for treatments that offer a real chance for durable remission. Impressively, 91 percent of follicular lymphoma patients in the ZUMA-5 study responded to a single infusion of [Yescarta] axicabtagene ciloleucel, including an estimated 74 percent of patients in a continued remission at 18 months, giving these patients much-needed hope and oncologists an important addition to the treatment armamentarium.”

ZUMA-5 is an ongoing, single-arm, open-label, multicenter trial evaluating 146 adult patients with relapsed or refractory iNHL who received at least two prior lines of systemic therapy, including the combination of an anti-CD20 monoclonal antibody and an alkylating agent. Efficacy was established on the basis of objective response rate (ORR) and duration of response (DoR) as assessed by an independent review committee.

Among the 146 patients evaluable for safety, Grade 3 or higher CRS and neurologic toxicities were observed in 8 percent and 21 percent of patients, respectively. The median time to onset of CRS and neurologic toxicities were four days (range: 1 to 20 days) and six days (range 1 to 79 days), respectively. The most common (≥10 percent) Grade 3 or higher adverse reactions included febrile neutropenia, encephalopathy, and infections with pathogen unspecified.

Yescarta carries a black box warning for the risks of CRS and neurologic toxicities, and is approved with a risk evaluation and mitigation strategy (REMS) due to these risks.

“As we look to bring the hope of survival to more patients in need, today’s FDA decision represents a real step forward in our commitment in hematologic malignancies,” said Christi Shaw, CEO of Kite. “Advancing CAR T therapies for patients across lymphomas remains a cornerstone of our cell therapy development program.”

Photo: Christi Shaw, CEO of Kite