The European Commission ( EC ) has granted marketing authorization for Breyanzi ( Lisocabtagene maraleucel; Liso-cel ), a CD19-directed chimeric antigen receptor ( CAR ) T cell immunotherapy, for the treatment of adult patients with relapsed or refractory ( R/R ) diffuse large B-cell lymphoma ( DLBCL ), primary mediastinal large B-cell lymphoma ( PMBCL ), and follicular lymphoma grade 3B ( FL3B ) after two or more lines of systemic therapy.
Breyanzi is delivered as a personalized treatment via a single infusion. Treatment with Breyanzi has demonstrated sustained complete responses in a high proportion of patients with R/R large B-cell lymphoma ( LBCL ) and a manageable and differentiated safety profile.
DLBCL is an aggressive blood disease accounting for one out of every three non-Hodgkin lymphoma ( NHL ) cases diagnosed, making it the most common form of NHL.
More than two-thirds of patients with DLBCL will not respond to or will relapse following second-line treatment and, historically, response rates for these patients are low with complete response rates ranging from 2% to 15%.
Despite recent treatment advancements, new options offering long-term clinical benefits are still needed.
The marketing authorization is based on results from the TRANSCEND NHL 001 study evaluating Breyanzi in adult patients with R/R DLBCL, PMBCL and FL3B, including those with a broad range of histologies and high-risk disease.
In 216 patients treated with Breyanzi and evaluable for efficacy, 73% of patients has achieved a response ( 95% CI: 67-78.5% ), including 53% who had minimal or no detectable lymphoma remaining following treatment ( complete response [ CR ]; 95% CI: 47-60% ).
Median duration of response was 20.2 months in all responders ( 95% CI: 8 – NR ), and for patients who achieved a complete response, median duration of response was 26.1 months ( 95% CI: 23 – NR ).
The safety of Breyanzi is based on pooled data from 314 patients with R/R LBCL treated with Breyanzi within a dose range of 44 to 120 x 10(6) CAR+ viable T cells across four studies ( TRANSCEND NHL 001, TRANSCEND WORLD, PLATFORM and OUTREACH ).
Any grade cytokine release syndrome ( CRS ) occurred in 39% of patients, 3% of whom experienced grade 3 or 4. The median time to onset was five days ( range: 1 to 14 days ) and the median duration was five days ( range: 1 to 17 days ).
Neurologic toxicities occurred in 26% of patients receiving Breyanzi, including grade 3 or 4 in 10% of patients. The median time to onset of the first neurologic toxicity event was nine days ( range: 1 to 66 days ); 99% of all neurologic toxicities occurred within the first eight weeks following Breyanzi infusion. The median duration of neurologic toxicity was 10 days ( range: 1 to 84 days ).
The most common grade more than 3 adverse reactions were neutropenia, anemia, thrombocytopenia, leukopenia, infection with an unspecified pathogen and febrile neutropenia.
TRANSCEND NHL 001
TRANSCEND NHL 001 is an open-label, multicenter, pivotal phase 1 study conducted in the U.S. to determine the safety, antitumor activity and pharmacokinetics of Breyanzi in patients with R/R LBCL, including DLBCL, high-grade B-cell lymphoma ( HGL ), PMBCL and FL3B.
The primary outcome measures included treatment-related adverse events, dose-limiting toxicities and objective response rate. Key secondary outcome measures included complete response rate, duration of response, progression-free survival and overall survival.
TRANSCEND WORLD is a single-arm, multi-cohort, multicenter, phase 2 study to determine the efficacy and safety of Breyanzi in patients with aggressive B-cell non-Hodgkin lymphoma.
The primary outcome measure was overall response rate. Secondary outcome measures included safety, complete response rate, event-free survival, progression-free survival, overall survival, duration of response, pharmacokinetics and health-related quality of life.
The study was conducted in Europe and Japan. ( Xagena )
Source: Bristol Myers Squibb ( BMS ), 2022