FDA Approves Brexucabtagene Autoleucel for Relapsed/Refractory Mantle Cell Lymphoma

The FDA has granted accelerated approval to brexucabtagene autoleucel (Tecartus), formerly known as KTE-X19, for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL).

Brexucabtagene autoleucel is now the first and only approved CAR T-cell therapy for this patient population. The agent was previously granted priority review and FDA breakthrough therapy designation.

“This approval marks the first CAR T-cell therapy approved for mantle cell lymphoma patients and represents a new frontier in the treatment of this disease,” Meghan Gutierrez, chief executive officer at the Lymphoma Research Foundation, said in a press release. “In the past decade, researchers have made significant progress in our understanding of this disease and we have seen an increase in clinical trials for patients, which we hope will continue to improve treatment strategies and the options available to people with mantle cell lymphoma. Today’s news builds upon this progress and provides hope to mantle cell patients and their loved ones.”

The approval was based on results from the ongoing, single-arm, open-label ZUMA-2 pivotal trial, which enrolled 74 adult patients with relapsed or refractory MCL who had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody therapy, and a Bruton tyrosine kinase inhibitor (ibrutinib or acalabrutinib).

The primary end point was objective response rate (ORR) per the Lugano Classification (2014), defined as the combined rate of complete responses and partial responses as assessed by an Independent Radiologic Review Committee (IRRC).

In total, 60 patients were evaluable for the efficacy analysis. Overall, 87% of patients responded to a single infusion of brexucabtagene autoleucel, including 62% who achieved a complete response. Of the overall study cohort, follow-up was at least 6 months after their first objective response.

Median duration of response has not yet been reached.

Eighty-two patients were evaluable for safety. Eighteen percent of patients experienced grade 3 or higher cytokine release syndrome (CRS) and 37% with neurologic events. Moreover, the most common (≥ 10 percent) grade 3 or higher adverse events observed were anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, pyrexia, hyponatremia, hypertension, infection-pathogen unspecified, pneumonia, hypocalcemia, and lymphopenia.

“Despite promising advances, there are still major gaps in treatment for patients with MCL who progress following initial therapy,” Michael Wang, MD, ZUMA-2 lead investigator and professor in the Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center, said in the release. “Many patients have high-risk disease and are more likely to keep progressing, even after subsequent treatments. The availability of [brexucabtagene autoleucel] as the first-ever cell therapy for patients with relapsed/refractory MCL provides an important option with a response rate of nearly 90 percent and early clinical evidence suggesting durable remissions in later lines of therapy.”

Notably, the FDA approved brexucabtagene autoleucel with a Risk Evaluation and Mitigation Strategy (REMS). The brexucabtagene autoleucel REMS has been combined with the axicabtagene ciloleucel (Yescarta) REMS and is now called the “Yescarta (axicabtagene ciloleucel) and Tecartus (brexucabtagene autoleucel) REMS Program.” The REMS program is intended to inform and educate healthcare professionals about the risks associated with the use of brexucabtagene autoleucel therapy, and training and certification on the REMS program will be an essential part of the final authorization for centers offering brexucabtagene autoleucel.

Reference:

U.S. FDA Approves Kite’s Tecartus™, the First and Only CAR T Treatment for Relapsed or Refractory Mantle Cell Lymphoma [news release]. Santa Monica, California. Published July 24, 2020. businesswire.com/news/home/20200724005428/en/. Accessed July 24, 2020.