CHMP Recommends Liso-cel in Pretreated R/R Follicular Lymphoma for Approval

The TRANSCEND FL trial showed that liso-cel elicited an ORR of 97.1% and a complete response rate of 94.2% in patients with follicular lymphoma.

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has recommended lisocabtagene maraleucel (liso-cel; Breyanzi), a CD19-directed CAR T-cell therapy, in adult patients with relapsed or refractory follicular lymphoma who have received at least 2 prior lines of systemic therapy, a press release from the developer, Bristol Myers Squibb, reported.¹

In May 2024, liso-cel also received accelerated approval in the indicated patient population from the FDA.² Currently, in the EU, liso-cel is approved in relapsed or refractory diffuse large B-cell lymphoma, high grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and grade 3B follicular lymphoma.

Supportive results come from the multicohort, open-label, phase 2 TRANSCEND FL (NCT04245839) trial evaluating the efficacy and safety of liso-cel in patients with relapsed or refractory follicular lymphoma or marginal zone lymphoma.

“As a company at the forefront of advancing therapies that transform outcomes for some of the most difficult-to-treat cancers, CAR T-cell therapies are a significant focus of our research, and [liso-cel] remains a cornerstone of our cell therapy portfolio and pipeline,” Anne Kerber, senior vice president and head of Late Clinical Development, Hematology, Oncology and Cell Therapy (HOCT) at Bristol Myers Squibb, stated in the press release.¹ “This is another important step in our commitment to delivering [liso-cel] to more patients across indications, as well as expanding into new regions, especially for diseases with continued unmet need such as relapsed or refractory [follicular lymphoma], which is considered incurable.”

Data from TRANSCEND FL showed that liso-cel elicited an overall response rate (ORR) of 97.1% (95% CI, 91.7%-99.4%) and a complete response (CR) rate of 94.2% (95% CI, 87.8%-97.8%); as well as sustained efficacy at 18 months, with a rate of 75.7% (95% CI, 66.0%-83.0%).

The TRANSCEND FL trial had an estimated enrollment total of 276 patients with histologically confirmed grade 1, 2, or 3a relapsed or refractory follicular lymphoma or marginal zone lymphoma within 6 months of screening.³

Patients received 30 mg/m² a day of intravenous fludarabine and 300 mg/m² for 3 days of intravenous cyclophosphamide prior to liso-cel infusion. Liso-cel was infused on day 1 at a dose of 100 x 10⁶ CAR-positive viable T cells at 2 to 7 days post completion of lymphodepleting chemotherapy.

Additional enrollment criteria included at least 1 prior therapy with anti-CD20 and alkylating agent, at least 2 prior lines of systemic therapy for those with follicular lymphoma, an ECOG performance status of 0 or 1, adequate organ function, and adequate vascular access for leukapheresis procedure.

Reasons for exclusion included evidence or history of composite diffuse large B-cell lymphoma and follicular lymphoma or transformed follicular lymphoma; World Health Organization duodenal-type follicular lymphoma subclassification; central nervous system–only involvement by malignancy; history of another primary malignancy that hasn’t been in remission for 2 years or more; prior CAR T-cell or other genetically modified cell therapy; history of human immunodeficiency virus; and allogenic-hematopoietic stem cell transplant within 90 days of leukapheresis.

The trial’s primary end point was ORR. Secondary end points included CR rate, duration of response, progression-free survival, overall survival, adverse events, pharmacokinetics, and the quality-of-life C30 questionnaire from the European Organization for Research and Treatment of Cancer.

The trial showed that the safety of liso-cel was comparable and consistent with previously reported data, with no new safety signals observed.

It is anticipated that the European Commission will deliver its final decision in approximately 2 months.

References

1. Bristol Myers Squibb receives positive CHMP opinion for CAR T cell therapy Breyanzi for relapsed or refractory follicular lymphoma. News release. Bristol Myers Squibb. January 31, 2025. Accessed January 31, 2025. https://tinyurl.com/nhr6tht7
2. FDA grants accelerated approval to lisocabtagene maraleucel for follicular lymphoma. News release. FDA. May 15, 2024. Accessed January 31, 2025. https://tinyurl.com/euust4sa
3. A study to evaluate the efficacy and safety of JCAR017 in adult subjects with relapsed or refractory indolent B-cell non-Hodgkin Lymphoma (NHL) (TRANSCEND FL). ClinicalTrials.gov. Updated January 15, 2025. Acccessed January 31, 2025. https://tinyurl.com/2kmukuwr