EU Approves Liso-Cel in R/R MCL With ≥ 2 Prior Lines of Systemic Therapy

The European Commission has approved lisocabtagene maraleucel (liso-cel; Breyanzi) as a treatment for adult patients with relapsed or refractory mantle cell lymphoma (MCL) following at least 2 lines of systemic therapy, including a Bruton’s tyrosine kinase (BTK) inhibitor, according to a press release from the developer, Bristol Myers Squibb.¹

Previously, in August 2025, the FDA accepted and granted priority review to a supplemental biologics license application for liso-cel in this indication; the FDA set a Prescription Drug User Fee Act date of December 5, 2025.²

Data supporting liso-cel in this patient population came from the MCL cohort of the phase 1 TRANSCEND NHL 001 trial (NCT02631044), which evaluated liso-cel in patients with relapsed or refractory B-cell non-Hodgkin lymphoma.

Among patients treated in the third-line or later setting, the overall response rate (ORR) was 82.7% (95% CI, 72.7%-90.2%), with a complete response (CR) rate of 71.6% (95% CI, 60.5%-81.1%). The median time to first response of CR or partial response (PR) was 0.95 months (range, 0.7-3.0), and 50.8% (95% CI, 29.2%-52.9%) of patients were still in response at 24 months.

“This approval for [liso-cel] in relapsed or refractory [MCL] marks another important step as we continue to deliver on the promise of cell therapy for more eligible patients across Europe—the fourth approval for [liso-cel] in Europe,” stated Emma Charles, senior vice president of the Europe Region at Bristol Myers Squibb, in the press release.¹ “While frontline therapies have advanced over the years for this rare but aggressive form of non-Hodgkin lymphoma, the vast majority of patients relapse or become resistant and [have] reduced survival outlook, leaving a critical need for new treatment options. [Liso-cel] has the opportunity to address a treatment gap for this patient population based on its demonstrated clinical benefit.”

A total of 104 patients were enrolled in the MCL cohort of the trial and underwent leukapheresis; among those patients, 88 received liso-cel.³ Eligible patients were 18 years or older with PET-positive MCL per Lugano 2014 criteria, which was relapsed or refractory after at least 2 prior lines of therapy including a BTK inhibitor, an alkylating agent, and a CD20-targeted agent.

Patients enrolled in the trial underwent leukapheresis for the manufacturing of liso-cel, with bridging chemotherapy permitted for disease control at the investigator’s discretion. Reconfirmation of PET-positive disease by investigator assessment was required prior to receipt of lymphodepleting chemotherapy. Liso-cel was administered 2 to 7 days later as 2 sequential intravenous infusions of CD8-positive and CD4-positive CAR T cells at a total target dose of 50 x 10⁶ CAR1 T cells (dose level 1) or 100 x 10⁶ CAR T cells (dose level 2).

The primary end points of the trial were the frequency and severity of adverse events, the probability of dose-limiting toxicities, and the ORR. The key secondary end point was the CR rate; additional end points included duration of response, progression-free survival, and overall survival.

Regarding safety, liso-cel exhibited a consistent and predictable safety profile in patients with MCL compared with what has been observed across various clinical trials and approved indications.

Notably, cytokine release syndrome (CRS) and neurologic toxicities occurred during the first 14 days post infusion. CRS occurred in 61% of patients, and 1% of patients experienced CRS of grade 3 or 4. The median time to CRS onset was 4 days (range, 1-10). Neurologic toxicities occurred in 31% of patients, and 9% experienced a neurologic event of grade 3 or 4. The median time to onset of the first neurologic toxicities was 8 days (range, 1-25).

The expanded approval applies to all European Union member states and the European Economic Area counties of Iceland, Norway, and Lichtenstein; it was noted that centralized marketing authorization does not include approval in the United Kingdom.

References

1. Bristol Myers Squibb receives approval from the European Commission to expand use of CAR T cell therapy Breyanzi for relapsed or refractory mantle cell lymphoma. News release. Bristol Myers Squibb. November 24, 2025. Accessed November 25, 2025. https://tinyurl.com/rp8b7ym4
2. Bristol Myers Squibb’s application for Breyanzi (lisocabtagene maraleucel) accepted for priority review by U.S. Food and Drug Administration (FDA) in fifth cancer type for relapsed or refractory marginal zone lymphoma (MZL). News release. Bristol Myers Squibb. August 4, 2025. Accessed November 25, 2025. https://tinyurl.com/mwuk2hst
3. Wang M, Siddiqi T, Gordon LI, et al. Lisocabtagene maraleucel in relapsed/refractory mantle cell lymphoma: primary analysis of the mantle cell lymphoma cohort from TRANSCEND NHL 001, a phase I multicenter seamless design study. J Clin Oncol. 2024;42(10):1146-1157. doi:10.1200/JCO.23.02214