FDA Approves Liso-Cel for R/R Mantle Cell Lymphoma After 2 Lines of Therapy

FDA

The FDA has approved lisocabtagene maraleucel (liso-cel; Breyanzi) for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have received at least 2 prior lines of systemic therapy, including a BTK inhibitor.¹

The approval was supported by data from the MCL cohort of the phase 1 TRANSCEND NHL 001 trial (NCT02631044), which showed that in patients (n = 68) with relapsed/refractory MCL previously treated at least 2 or more lines of therapy, including a BTK inhibitor, liso-cel elicited an overall response rate (ORR) of 85.3% (95% CI, 74.6%-92.7%), including a complete response (CR) rate of 67.6% (95% CI, 55.2%-78.5%).

Additionally, at a median follow-up of 22.2 months (95% CI, 16.7-22.8), patients experienced a median time to response of 1 month (range, 0.7-3), and a median duration of response (DOR) of 13.3 months (95% CI, 6.0-23.3). Notably, 51.4% (95% CI, 37.5%-63.7%) of responders were still in response at 12 months, and 38.8% (95% CI, 25%-52.4%) remained in response at 18 months.

“With [liso-cel], we are delivering on the promise of cell therapy by offering a definitive treatment option for some of the most difficult-to-treat lymphomas,” Bryan Campbell, senior vice president and head of Commercial Cell Therapy at Bristol Myers Squibb, stated in a news release. “We are proud of the advances we are making to bring our differentiated CAR T-cell therapy to the most patients across indications and lines of therapy to ensure treatment options that provide improved outcomes are available when most needed.”

TRANSCEND NHL 001 was an open-label, multicenter, single-arm trial that evaluated the safety, pharmacokinetics, and antitumor activity of liso-cel in patients with relapsed/refractory B-cell non-Hodgkin lymphoma, including diffuse large B-cell lymphoma, high-grade B-cell lymphoma, primary mediastinal B-cell lymphoma, grade 3B follicular lymphoma, and MCL.

In the MCL cohort, patients needed to be at least 18 years of age with PET-positive MCL per Lugano 2014 criteria. Patients were required to have relapsed/refractory disease after at least 2 prior lines of therapy, including a BTK inhibitor, an alkylating agent, and a CD20-targeted agent. Notably, the study allowed enrollment for patients with moderate renal and cardiac dysfunction; secondary central nervous system lymphoma; or prior receipt of autologous or allogeneic hematopoietic stem cell transplant.²

After enrolled patients underwent leukapheresis, bridging chemotherapy was permitted for disease control during the manufacturing of liso-cel, at the discretion of the investigator. Prior to receiving the CAR T-cell therapy, patients underwent 3 days of lymphodepleting chemotherapy consisting of fludarabine at 30 mg/m² and cyclophosphamide at 300 mg/m² per day. Liso-cell was administered 2 to 7 days after the conclusion of lymphodepletion at a target dose of 50 × 10⁶ CAR+ T cells (dose level 1) or 100 × 10⁶ CAR+ T cells (dose level 2).

The primary end points included safety, probability of dose-limiting toxicities, and ORR. Secondary end points were CR rate, DOR, progression-free survival (PFS), overall survival (OS), cellular kinetic parameters, and health-related quality of life.

Among the 104 patients with MCL who underwent leukapheresis, 88 received liso-cel at dose level 1 (n = 6) or dose level 2 (n = 82). Eighty-three patients were included in the efficacy set, and 74 patients were part of the primary analysis set.

In the study's primary analysis published in The Journal of Clinical Oncology, the ORR in the primary analysis set was 86.5% (95% CI, 76.5%-93.3%; P <.0001), and the CR rate was 74.3% (95% CI, 62.8%-83.8%; P <.0001). The ORR and CR rate in the efficacy set were 83.1% (95% CI, 73.3%-90.5%) and 72.3% (95% CI, 61.4%-81.6%), respectively. Accounting for all patients who underwent leukapheresis, the ORR was 70.2% (95% CI, 60.4%-78.8%), and the CR rate was 61.5% (95% CI, 51.5%-70.9%).

In the efficacy set, the median DOR was 15.7 months (95% CI, 6.2-24.0), the median PFS was 15.3 months (95% CI, 6.6-24.9), and the median OS was 18.2 months (95% CI, 12.9-36.3).

Regarding safety, 54% of patients with relapsed/refractory B-cell non-Hodgkin lymphoma treated with liso-cel across clinical trials (n = 702) experienced any-grade cytokine release syndrome (CRS), and the rate of grade 3 or higher CRS was 3.2%. The median time to onset of CRS was 5 days (range, 1-63).¹

Any grade neurologic toxicities occurred in 31% of patients, and 10% of patients had grade 3 or higher neurologic toxicities. The median time to onset of these toxicities was 8 days (range, 1-63), and neurologic toxicities resolved in 88% of patients with a median duration of 7 days (range, 1-119).

“The approval of [liso-cel] brings a new CAR T-cell therapy option to patients battling relapsed or refractory MCL,” Meghan Gutierrez, chief executive officer of the Lymphoma Research Foundation, added in a news release. “Each advance in treatment represents important progress in improving outcomes for patients, and this news builds upon this progress with a new potentially transformative treatment where there are currently limited options. We are thankful for the families and the researchers involved in making this approval a reality for those living with this disease.”

References

1. U.S. Food and Drug Administration approves Bristol Myers Squibb’s Breyanzi as a new CAR T cell therapy for relapsed or refractory mantle cell lymphoma. News release. Bristol Myers Squibb. May 30, 2024. Accessed May 30, 2024. https://news.bms.com/news/details/2024/U.S.-Food-and-Drug-Administration-Approves-Bristol-Myers-Squibbs-Breyanzi-as-a-New-CAR-T-Cell-Therapy-for-Relapsed-or-Refractory-Mantle-Cell-Lymphoma/default.aspx
2. 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