Lisocabtagene Maraleucel (CAR T-Cell Therapy) Receives FDA Approval for Mantle Cell Lymphoma

On May 30, 2024, the US Food and Drug Administration (FDA) approved the CAR T-cell therapy lisocabtagene maraleucel (Breyanzi, Juno Therapeutics, Inc.) for relapsed or refractory mantle cell lymphoma (MCL) in patients who have received at least two different systemic treatments and a Bruton tyrosine kinase inhibitor (BTKi). The approval represents an important advance for patients with limited treatment options.

Lisocabtagene maraleucel, marketed as Breyanzi, uses genetically modified T cells to target and destroy cancer cells as a CAR T-cell therapy. The patient's own T cells are collected and genetically reprogrammed in a laboratory to recognize and attack cancer cells.

Mantle cell lymphoma (MCL) is a rare non-Hodgkin lymphoma arising from the "mantle" zone of lymph nodes. It usually occurs in men and people over 60 and can follow an aggressive course, spreading to the bone marrow and other organs. MCL is considered a cancer that can resist treatment and frequently recur.

Previous FDA Approvals for Breyanzi

• May 15, 2024: Approved for relapsed or refractory follicular lymphoma.
• March 14, 2024: Approved as the first and only CAR T-cell therapy for adults with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
• June 24, 2022: Approved for large B-cell lymphoma that has relapsed or is refractory after one previous treatment.
• February 5, 2021: Approved for adults with relapsed or refractory large B-cell lymphoma.

Previous CAR T-Cell Treatments for MCL

Another CAR T-cell treatment had previously been approved for mantle cell lymphoma: brexucabtagene autoleucel (Tecartus). On July 24, 2020, the FDA approved it for relapsed or refractory MCL. Tecartus works by genetically modifying and reprogramming patients' own T cells to recognize and destroy cancer cells. In ZUMA-2, its overall response rate was 87% and its complete response rate was 62%.

TRANSCEND-MCL: Efficacy and Safety Data

Lisocabtagene maraleucel's efficacy was evaluated in the open-label, multicenter, single-arm TRANSCEND-MCL study. It included adults who had received at least two treatment lines and a BTKi, an alkylating agent and an anti-CD20 agent, had an ECOG performance status of 1 or less, and had adequate bone marrow function. No prespecified blood-count threshold was used; patients judged to have adequate marrow function were considered able to receive lymphodepleting chemotherapy.

Treatment and Efficacy Results

Patients received a single dose of lisocabtagene maraleucel 2 to 7 days after completing lymphodepleting chemotherapy (fludarabine 30 mg/m²/day and cyclophosphamide 300 mg/m²/day for 3 days). The primary efficacy analysis included 68 patients with MCL who had received at least 2 treatment lines and had PET-positive disease.

An independent review committee (IRC) assessed responses using the 2014 Lugano classification:

• The overall response rate was 85.3% (95% CI: 74.6, 92.7).
• The complete response rate was 67.6% (95% CI: 55.2, 78.5).
• After a median follow-up of 22.2 months (95% CI: 16.7, 22.8), median duration of response (DOR) was 13.3 months (95% CI: 6.0, 23.3).

Adverse Events and Risks

The most common nonlaboratory adverse events (more than 20%) were cytokine release syndrome (CRS), fatigue, musculoskeletal pain, encephalopathy, edema, headache and decreased appetite. Because of fatal or life-threatening CRS and neurological toxicities, the FDA approved lisocabtagene maraleucel with a Risk Evaluation and Mitigation Strategy (REMS).

Recommended Dose and Use

The recommended lisocabtagene maraleucel dose is 90 to 110 × 10⁶ CAR-positive viable T cells, with CD4 and CD8 components in a 1:1 ratio.

Conclusion

FDA approval of lisocabtagene maraleucel offers a promising new treatment option for patients with relapsed or refractory mantle cell lymphoma. This innovative treatment has the potential to improve survival and quality of life for patients with MCL.