FDA Approves Liso-Cel in Mantle Cell Lymphoma

The FDA approved the chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel (liso-cel; Breyanzi) for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after treatment with 2 or more lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor.¹

The approval is supported by findings from the MCL cohort of the TRANSCEND NHL 001 study (NCT02631044). Enrolled patients were adults with relapsed or refractory MCL who had previously received at least 2 or more prior lines of therapy, including a BTK inhibitor. Of the 68 patients treated with liso-cel and evaluated for efficacy, 85.3% (95% CI, 74.6-92.7) responded to treatment, and 67.6% of patients (95% CI, 55.2-78.5) achieved a complete response (CR). Responses were rapid and durable with a median time to response of 1 month (range, 0.7-3).

At a median follow-up of 22.2 months (95% CI, 16.7-22.8), the median duration of response was 13.3 months (95% CI, 6.0-23.3). A total of 51.4% of responders (95% CI, 37.5-63.7) continued to have a response at 12 months, and 38.8% (95% CI, 25-52.4) remained in response at 18 months.

Further, findings from the primary analysis were published in the Journal of Clinical Oncology, and showed there to be an overall response rate of 83.1% (95% CI, 73.3-90.5) and a CR rate of 72.3% (95% CI, 61.4-81.6) at the time of the analysis. Here, the median duration of response was 15.7 months (95% CI, 6.2-24.0).

Additionally, findings from a subgroup analysis of the TRANSCEND NHL 001 study presented at the 2024 Tandem Meetings on Transplantation & Cellular Therapy showed a PFS of 15.3 months (95% CI, 6.6-24.9) in patients with Ki-67 of 30% or higher, 24.0 months (95% CI, 2.4-not reached [NR]) in patients with Ki-67 under 30%, 7.4 months (95% CI, 3.3-NR) in patients with a TP53 mutations, and 7.8 months (95% CI, 3.1-NR) for patients with blastoid morphology.³

Safety findings were presented at the 17th International Congress of Malignant Lymphoma held in Lugano, Switzerland.⁴ The most common treatment-emergent adverse events (TEAEs) of grade 3 or higher were neutropenia (56%), anemia (37.5%), thrombocytopenia (25%), and hypophosphatemia (9%). For all-grade TEAEs, cytokine release syndrome (61%), neutropenia (59%), anemia (44%), and fatigue (35%) were the most common.

The maximum tolerated dose was not reached, while 31 dose-limiting toxicities (DLTs) were observed. Two patients experienced DLTs at dose level 2. Additionally, 4 patients experienced a grade 5 adverse event (AE), and 3 were considered related to liso-cel.

About TRANSCEND NHL 001

TRANSCEND NHL 001 is an open-label phase 1 study determining the safety, pharmacokinetics, and antitumor activity of liso-cel in patients with various non-Hodgkin lymphomas, including MCL.5 The primary end points are incidence of treatment-related AEs, DLTs, and ORR. Secondary end points include CR rate, DOR, PFS, OS, health-related quality of life, and pharmacokinetics.

Patients received either 1 or 2 intravenous injections of liso-cel following lymphodepletion therapy.

About Liso-Cel

Liso-cel is a CD19-directed CAR T-cell therapy for the treatment of patients with large B-cell lymphomas (LBCL).6 Liso-cel is recommended by the National Comprehensive Cancer Network for patients with LBCL who are relapsed or refractory after 12 or more months regardless or transplant eligibility and patients who are transplant-ineligible regardless of time to relapse.

In March 2024, liso-cel was approved by the FDA for the treatment of chronic lymphocytic leukemia and small lymphocytic lymphoma based on findings from the TRANSCEND CLL 004 study (NCT03331198).

***In May 2024, liso-cel was also approved for the treatment of patients with follicular lymphoma.

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. FDA. May 30, 2024. Accessed May 30, 2024. https://news.bms.com/news/corporate-financial/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. Published online December 10, 2023. doi:10.1200/JCO.23.02214

3. Palomba ML, Siddiqi T, Gordon LI, et al. Lisocabtagene maraleucel (liso-cel) in patients (Pt) with R/R MCL: subgroup analyses in pts with high-risk disease features from the MCL cohort of the TRANSCEND NHL 001. Presented at: 2024 Transplantation and Cellular Therapies Meeting; February 21-24, 2024; San Antonio, TX. Abstract 17.

4. Wang M, Siddiqi T, Gordon LI, et al. Lisocabtagene maraleucel in R/R MCL: primary analysis results from the MCL cohort of the single-arm, multicenter, seamless design TRANSCEND NHL 001 study. Presented at: 17th International Conference on Malignant Lymphoma; June 13-17, 2023; Lugano, Switzerland. Accessed March 13, 2024. https://tinyurl.com/8x9vpfa3

5. Study evaluating the safety and pharmacokinetics of JCAR017 in B-cell non-Hodgkin lymphoma (TRANSCEND-NHL-001). ClinicalTrials.gov. Updated March 3, 2023. Accessed March 13, 2024. https://tinyurl.com/2r43ykrj

6. Breyanzi. Accessed March 13, 2024. https://tinyurl.com/bdfkb7tn