Liso-Cel/Breyanzi Approved for Relapsed/Refractory Mantle Cell Lymphoma

Liso-Cel/Breyanzi Approved for Relapsed/Refractory Mantle Cell Lymphoma

This is a developing story and will be updated with new information as it becomes available.

The FDA has approved Bristol Myers Squibb’s lisocabtagene maraleucel (liso-cel, marketed as Breyanzi), an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy, for treating adults with relapsed/refractory (r/r) mantle cell lymphoma (MCL) who have been previously treated with at least 2 lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor.¹ MCL is the fourth subtype of nonHodgkin lymphoma that liso-cel has been approved for use in and the product now constitutes the CAR-T with FDA approval for the broadest range of B-cell malignancies

“With Breyanzi, 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, PharmD, the senior vice president and head of commercial for Cell Therapy at Bristol Myers Squibb, said in a statement.¹ “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.”

The agency's decision was based off of data from the MCL cohort in the phase 1 TRANSCEND NHL 001 clinical trial (NCT02631044). Among 68 evaluated patients in the trial with r/r MCL who had previously received 2 or more previous lines of therapy, including a BTK inhibitor, 85.3% (95% CI: 74.6-92.7) achieved a response to liso-cel and 67.6% (95% CI: 55.2-78.5) attained a complete response (CR). Furthermore, the median time to response ranged from 0.7 to 3 months (median, 1 month) and the median duration of response (DOR) was 13.3 months (95% CI: 6.0-23.3); median follow-up was 22.2 months (95% CI: 16.7-22.8). Bristol Myers Squibb pointed out that 51.4% of the patients who responded (95% CI: 37.5-63.7) maintained their response at 12 months posttreatment and that 38.8% of patients who responded (95% CI: 25-52.4) maintained their response at 18 months posttreatment. The company also noted that in a primary analysis from the trial published in the Journal of Clinical Oncology that included 83 patients treated at either dose level 1 or dose level 2, the overall response rate was 83.1% (95% CI: 73.3-90.5), the CR rate was 72.3% (95% CI: 61.4 to 81.6), the median DOR was 15.7 months (95% CI: 6.2 to 24.0), and progression-free survival was 15.3 months (95% CI: 6.6 to 24.9).

In terms of safety, Bristol Myers Squibb noted that liso-cel has shown a consistent safety profile across multiple clinical trials evaluating 702 patients. In that data set, cytokine release syndrome (CRS) of any grade occurred in 54% of patients and CRS of grade 3 or higher occurred in 3.2% of patients. Neurologic events (NEs) of any grade were observed in 31% of patients, with grade 3 or higher NEs occurring in 10% of patients. The time to onset for CRS ranged from 1 to 63 days (median, 5) and the time to onset for NEs also ranged from 1 to 63 days (median, 8). Bristol Myers Squibb stated that in 88% of patients NEs resolved with a duration ranging from 1 to 119 days (median, 7).

“There have been few advances in the treatment of relapsed or refractory MCL, and prognosis worsens for patients after each subsequent relapse, often leaving them with high disease burden and difficulty achieving deep and durable responses,” Michael Wang, MD, the study's lead investigator and the Puddin Clarke Endowed Professor in the Department of Lymphoma and Myeloma in the Division of Cancer Medicine at University of Texas MD Anderson Cancer Center, added to the statement.¹ “The approval of Breyanzi offers an important new CAR-T treatment option with high rates of lasting responses and a consistent safety profile, which is critically important for these patients who currently have limited options to treat this aggressive disease.”

Notably, earlier this month liso-cel received accelerated approval from the FDA for treating adults with r/r follicular lymphoma who have received 2 or more prior lines of systemic therapy.² Breyanzi was also recently approved by the FDA for treating chronic lymphocytic leukemia or small lymphocytic lymphoma in March 2024.³ The therapy is also approved for the second-line treatment of r/r large B-cell lymphoma (LBCL) in the US, Japan, and Europe, and for relapsed and refractory LBCL after 2 or more lines of systemic therapy in Japan, Europe, Switzerland, and Canada.

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://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-lisocabtagene-maraleucel-follicular-lymphoma
2. FDA grants accelerated approval to lisocabtagene maraleucel for follicular lymphoma. News release. FDA. May 15, 2024. Accessed May 30, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-lisocabtagene-maraleucel-follicular-lymphoma
3. U.S. FDA Approves Bristol Myers Squibb’s Breyanzi ® as the First and Only CAR T Cell Therapy for Adults with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL). News release. Bristol Myers Squibb. March 14, 2024. Accessed May 30, 2024. https://news.bms.com/news/corporate-financial/2024/U.S.-FDA-Approves-Bristol-Myers-Squibbs-Breyanzi--as-the-First-and-Only-CAR-T-Cell-Therapy-for-Adults-with-Relapsed-or-Refractory-Chronic-Lymphocytic-Leukemia-CLL-or-Small-Lymphocytic-Lymphoma-SLL/default.aspx