Bristol Myers Squibb announced the U.S. Food and Drug Administration (FDA) has granted approval for Breyanzi® (lisocabtagene maraleucel; liso-cel), a CD19-directed chimeric antigen receptor (CAR) T cell therapy, for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have received at least two prior lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor. This FDA approval marks the fourth distinct subtype of non Hodgkin lymphoma for which Breyanzi is approved, making it the CAR T cell therapy available to treat the broadest array of B-cell malignancies. In relapsed or refractory MCL, Breyanzi is delivered as a one-time infusion with a single dose containing 90 to 110 x 106 CAR-positive viable T cells.

see the Important Safety Information section below, including Boxed WARNINGS for Breyanzi regarding Cytokine Release Syndrome (CRS), Neurologic Toxicities, and Secondary Hematological Malignancies.MCL is a rare but aggressive form of non-Hodgkin lymphoma, and many patients relapse or become resistant to frontline therapies. Currently, MCL is considered an incurable disease, and response rates and duration of response tend to decrease with each additional relapse. The approval of Breyanzi is based on results from the MCL cohort of TRANSCEND NHL 001, which enrolled adults with relapsed or refractory MCL who had previously received at least two or more prior lines of therapy, including a BTK inhibitor.

Based on the U.S. Prescribing Information (USPI), in patients treated with Breyanzi and evaluated for efficacy (n=68), 85.3% (95% CI: 74.6-92.7) responded to treatment, with 67.6% (95% CI: 55.2-78.5) achieving a complete response (CR). Responses were assessed per the 2014 Lugano classification and required bone marrow biopsy to confirm CR. Responses were rapid and durable with a median time to response of one month (range: 0.7-3) and median duration of response of 13.3 months (95% CI: 6.0-23.3) with a median follow-up of 22.2 months (95% CI: 16.7-22.8).

More than half (51.4%; 95% CI: 37.5-63.7) of responders remained in response at 12 months, and 38.8% (95% CI: 25-52.4) of responders remained in response at 18 months. Results from the primary analysis published in the Journal of Clinical Oncology (JCO) (n=83; DL1 + DL2) showed an overall response rate of 83.1% (95% CI: 73.3-90.5) and a CR rate of 72.3% (95% CI: 61.4 to 81.6). Median duration of response 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).

Breyanzi has exhibited a consistent safety profile across clinical trials (n=702) with any grade cytokine release syndrome (CRS) occurring in 54% of patients, including Grade >3 CRS in 3.2% of patients. The median time to onset was 5 days (range: 1 to 63 days). Any grade neurologic events (NEs) were reported in 31% of patients, including Grade >3 in 10% of patients.

The median time to onset of NEs was 8 days (range: 1 to 63 days). NEs resolved in 88% of patients with a median duration of 7 days (range: 1 to 119 days). The safety profile of Breyanzi allows for the option of outpatient treatment and management of patients.

Breyanzi was administered in the inpatient and outpatient setting in the MCL cohort of TRANSCEND NHL 001. To support this additional indication for Breyanzi, Bristol Myers Squibb has made continuous investments to increase manufacturing capacity and is prepared to meet demand for Breyanzi. TRANSCEND NHL 001 (NCT02631044) is an open-label, multicenter, pivotal, Phase 1, single-arm, seamless-design study to determine the safety, pharmacokinetics and antitumor activity of Breyanzi in patients with relapsed or refractory B-cell non-Hodgkin lymphoma, including diffuse large B-cell lymphoma, high-grade B-cell lymphoma, primary mediastinal B-cell lymphoma, follicular lymphoma Grade 3B and mantle cell lymphoma.

The primary outcome measures are treatment-related adverse events, dose-limiting toxicities and overall response rate. Secondary outcome measures include complete response rate, duration of response, and progression-free survival. BREYANZI is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of: adult patients with large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B, who have: refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy; or refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age; or relapsed or refractory disease after two or more lines of systemic therapy.

Limitations of Use: BREYANZI is not indicated for the treatment of patients with primary central nervous system lymphoma. adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least 2 prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor. This indication is approved under accelerated approval based on response rate and duration of response.

Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). adult patients with relapsed or refractory follicular lymphoma (FL) who have received 2 or more prior lines of systemic therapy. This indication is approved under accelerated approval based on response rate and duration of response.

Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have received at least 2 prior lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor. Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred following treatment with BREYANZI.

In clinical trials of BREYANZI, which enrolled a total of 702 patients with non-Hodgkin lymphoma (NHL), CRS occurred in 54% of patients, including = Grade 3 CRS in 3.2% of patients. The median time to onset was 5 days (range: 1 to 63 days). CRS resolved in 98% of patients with a median duration of 5 days (range: 1 to 37 days).

One patient had fatal CRS and 5 patients had ongoing CRS at the time of death. The most common manifestations of CRS (=10%) were fever, hypotension, tachycardia, chills, hypoxia, and headache.