On February 5, 2021, the U.S. Food and Drug Administration (FDA) approved lisocabtagene maraleucel (Breyanzi®) for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified—including DLBCL arising from indolent lymphoma—high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B.
Lisocabtagene maraleucel is a CD19-directed chimeric antigen receptor (CAR) T-cell immunotherapy. It consists of autologous T cells that are genetically modified to produce a CAR protein, allowing the T cells to identify and eliminate CD19-expressing normal and malignant cells.
Efficacy was evaluated in a single-arm, open-label, multicenter trial (TRANSCEND; NCT02631044) that observed lisocabtagene maraleucel, preceded by lymphodepleting chemotherapy, in adults with relapsed or refractory large B-cell lymphoma after they received at least two lines of therapy.
Of the 192 patients evaluable for response, overall response rate (ORR) per independent review committee assessment was 73% (95% CI = 67, 80) with a complete response (CR) rate of 54% (95% CI = 47, 61). The median time to first response was one month. Of the 104 patients who achieved CR, 65% had remission lasting at least six months and 62% had remission lasting at least nine months. The estimated median duration of response (DOR) was not reached (95% CI = 16.7 months, not reached) in patients who achieved CR. Estimated median DOR among patients with partial response was 1.4 months (95% CI = 1.1, 2.2).
Cytokine release syndrome (CRS) occurred in 46% of patients, with 4% experiencing grade 3 or higher, and neurologic toxicity occurred in 35%, with 12% experiencing grade 3 or higher. Three patients had fatal neurologic toxicity. Other grade 3 or higher adverse reactions included infections (19%) and prolonged cytopenias (31%).
FDA approved lisocabtagene maraleucel with a risk evaluation and mitigation strategy because of the risk of fatal or life-threatening CRS and neurologic toxicities.
The recommended regimen is a single dose containing 50 to 110 x 106 CAR-positive viable T cells with a 1:1 ratio of CD4 and CD8 components, administered via IV infusion and preceded by fludarabine and cyclophosphamide for lymphodepletion. Lisocabtagene maraleucel is not indicated for the treatment of patients with primary central nervous system lymphoma.
View FDA's approved cellular and gene therapy products webpage for more product information.
FDA granted the application priority review and regenerative medicine advanced therapy, breakthrough, and orphan drug designations. A description of FDA expedited programs is in the Guidance for Industry—Expedited Programs for Serious Conditions—Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.
For assistance with single-patient oncology investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.