The U.S. Food and Drug Administration (FDA) has approved lisocabtagene maraleucel (Breyanzi), developed by Juno Therapeutics, Inc., for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have undergone at least two prior lines of systemic therapy, including a Bruton tyrosine kinase inhibitor (BTKi). This approval marks a significant advancement in the therapeutic landscape for MCL, providing a new option for patients with limited alternatives.
Image Source: Vinoth Khandelwal
Lisocabtagene maraleucel’s approval was facilitated through the FDA’s expedited programs, reflecting its potential to address unmet medical needs. The application received priority review and orphan drug designation, underscoring its significance in treating a rare and serious condition. The regulatory review was supported by the Assessment Aid, a voluntary submission to streamline the FDA’s evaluation process.
Lisocabtagene maraleucel, marketed under the brand name Breyanzi, is a chimeric antigen receptor (CAR) T cell therapy. The recommended dose for patients is 90 to 110 × 10^6 CAR-positive viable T cells, with a balanced ratio of CD4 and CD8 components. This innovative therapy harnesses the patient’s own immune system to target and eliminate malignant cells. The technology behind lisocabtagene maraleucel involves genetically modifying the patient’s T cells to express a CAR that specifically targets the CD19 antigen on the surface of B cells, including malignant MCL cells. Once reintroduced into the patient’s body, these engineered T cells seek out and destroy cancerous cells.
The efficacy and safety of lisocabtagene maraleucel were evaluated in the TRANSCEND-MCL trial (NCT02631044). This open-label, multicenter, single-arm study included adult patients with relapsed or refractory MCL who had previously received at least two lines of therapy, including a BTKi, an alkylating agent, and an anti-CD20 agent. Patients were required to have a PET-positive disease at the study baseline or after bridging therapy, and a minimum ECOG performance status of 1 or less. Adequate bone marrow function for lymphodepleting chemotherapy was a prerequisite for participation. The main efficacy measure was the overall response rate (ORR), defined by the percentage of patients achieving either a complete response (CR) or partial response (PR) post-infusion, as assessed by an independent review committee using the 2014 Lugano classification. The study reported an ORR of 85.3%, with a CR rate of 67.6%. The median duration of response was 13.3 months after a median follow-up of 22.2 months.
Mantle cell lymphoma (MCL) is an aggressive type of non-Hodgkin lymphoma characterized by poor prognosis and limited treatment options upon relapse. Patients often experience frequent relapses and require novel therapies to improve survival outcomes. The approval of lisocabtagene maraleucel provides a promising option for patients who have exhausted conventional therapies.
Dr. Vinoth Khandelwal, Ph.D.
