EMA Reviews Bristol Myers Squibb’s Application to Expand Breyanzi as Second-Line Therapy for Relapsed or Refractory Large B-Cell Lymphoma

Compiled by Fan Dongdong

Recently, Bristol-Myers Squibb announced that the Type II variation application for Breyanzi has been validated by the European Medicines Agency (EMA), and the EMA has initiated the centralized review process.

This application primarily aims to expand the indications for Breyanzi (lisocabtagene maraleucel) to include adult patients with diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBCL), primary mediastinal large B-cell lymphoma (PMBCL), and grade 3B follicular lymphoma (FL3B). These patients are either refractory or have relapsed within 12 months of initial treatment and are candidates for hematopoietic stem cell transplantation (HSCT).

Anne Kerber, Senior Vice President of Cell Therapy Development at Bristol-Myers Squibb, stated that the incidence of relapsed or refractory large B-cell lymphoma after first-line treatment is very high, and few patients benefit from stem cell transplantation, which has become the standard second-line treatment for this disease over the past 30 years. Kerber noted that Bristol-Myers Squibb looks forward to collaborating with the European EMA, aiming to establish Breyanzi as a new second-line care standard for patients with relapsed or refractory large B-cell lymphoma, and ultimately bring the therapeutic potential of cell therapy to more such patients.

This Type II variation application was supported by data from the pivotal Phase 3 TRANSFORM study, which evaluated Breyanzi as a second-line treatment for adult patients with relapsed or refractory LBCL compared to the standard regimen consisting of salvage chemotherapy, high-dose chemotherapy, and HSCT.

The trial results showed that Breyanzi significantly improved event-free survival (EFS) and demonstrated clinically and statistically significant improvements in complete response rate and progression-free survival. Breyanzi also exhibited a well-established safety profile, with very low incidences of severe cytokine release syndrome (CRS) and neurological events. No new safety signals were observed in this second-line treatment, consistent with the safety profile observed with Breyanzi in third-line treatment.

LBCL is an aggressive hematologic malignancy and one of the most common types of non-Hodgkin lymphoma. Approximately 40% of patients will develop refractory or relapsed disease after first-line treatment. High-dose chemotherapy followed by autologous stem cell transplantation has been the mainstay of second-line treatment and historically has been almost the only treatment option for patients after the failure of first-line therapy.

Although an estimated 50% of patients with primary refractory or relapsed disease are considered candidates for stem cell transplantation, only about 25% of these patients eventually receive stem cell transplantation. Breyanzi is a differentiated CD-19 directed CAR-T cell therapy, which has been approved in the EU for the treatment of adult patients with relapsed or refractory (R/R) diffuse DLBCL, primary mediastinal large B-cell lymphoma PMBCL, and FL3B after two or more lines of systemic therapy.

The supplemental Biologics License Application for Breyanzi for the treatment of relapsed or refractory LBCL after failure of first-line therapy is currently under priority review by the U.S. FDA, with a Prescription Drug User Fee Act (PDUFA) target date previously set by the regulatory agency for June 24, 2022. In addition, Japan's Ministry of Health, Labour and Welfare is also reviewing a new drug application for Breyanzi for second-line treatment of patients with relapsed or refractory LBCL. However, to date, Breyanzi has not been approved for second-line treatment of LBCL in any country or region.

Reference Source: European Medicines Agency Validates Bristol Myers Squibb's Application for CAR T Cell Therapy Breyanzi in Relapsed or Refractory Large B-cell Lymphoma After First-Line Therapy