Bristol Myers Squibb’s Breyanzi (lisocabtagene maraleucel) Demonstrates Superior Efficacy Over Two-Decade Standard of Care in Second-Line Treatment of Relapsed or Refractory Large B-Cell Lymphoma

December 26, 2021 /BioValleyBIOON/ -- Bristol-Myers Squibb (BMS) recently announced the pre-specified interim analysis data from the pivotal Phase 3 TRANSFORM study (NCT03575351). This is a global, multicenter, randomized Phase 3 study evaluating the efficacy and safety of the CD19 CAR-T cell therapy Breyanzi (lisocabtagene maraleucel, liso-cel) as a second-line treatment for adult patients with relapsed or refractory large B-cell lymphoma (R/R LBCL). The interim analysis showed thatThe study met its primary endpoint and key secondary endpoints: in patients with relapsed or refractory (R/R) LBCL who are eligible for HSCT, compared to the current standard of care regimen (salvage chemotherapy, followed by high-dose chemotherapy [HDCT] and hematopoieticStem CellsCompared with transplantation [HSCT], Breyanzi has significant efficacy and good safety.

Specifically, the median follow-up was 6.2 months,Compared with standard care, Breyanzi significantly extended event-free survival (EFS)., Primary endpoint of the study): The median EFS in the Breyanzi treatment group was 10.1 months (95% CI: 6.1-NR), compared to 2.3 months (95% CI: 2.2-4.3) in the standard care group. Breyanzi reduced the risk of EFS events by 65% compared to standard care (HR=0.349; p<0.0001).

Breyanzi is an autologous, CD19-directed, chimeric antigen receptor (CAR) T-cell therapy with a defined composition and 4-1BB co-stimulatory domain. Breyanzi consists of purified CD8+ and CD4+ T cells in a specific ratio (1:1), and the 4-1BB signaling enhances the expansion and persistence of Breyanzi.

In February 2020, Breyanzi was approved by the United States.FDAApproved for the treatment of adult patients with R/R LBCL who have previously received two or more systemic therapies, including unspecified diffuse large B-cell lymphoma (DLBCL, including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma (HGBL), primary mediastinal large B-cell lymphoma (PMBCL), and grade 3B follicular lymphoma. Breyanzi is not indicated for the treatment of patients with primary central nervous system (CNS) lymphoma.

TRANSFORM Study ResultsFirst demonstrated in patients with relapsed or refractory LBCL, a treatment method outperforms standard high-dose chemotherapy andStem CellsTransplant Therapy More Effective, and for the first time demonstrated the potential of CD19-directed CAR-T cell therapy as a second-line treatment.

University of Colorado Cancer Center Hematology Blood MalignanciesTumorAndStem CellsManali Kamdar, director of the transplant department, commented: "For more than 20 years, salvage chemotherapy followed by high-dose chemotherapy andStem CellsTransplantation has always been a cornerstone of care for patients with second-line relapsed or refractory LBCL, but only a small proportion of patients achieve long-term benefits through this approach. In the phase 3 TRANSFORM study, Breyanzi outperformed the current standard of care for patients with refractory disease, and these results have the potential to pave the way for a shift in treatment paradigms, where patients who experience disease relapse or are non-responsive to first-line therapy can be treated with personalized CAR-T cell therapy to improve treatment outcomes.

TRANSFORM is a global, randomized, multicenter study being conducted in adult patients with large B-cell lymphoma (LBCL) who are primary refractory or relapsed within 12 months of initial treatment and are eligible for stem cell transplantation. The study is evaluating the efficacy and safety of the CD19 CAR-T cell therapy Breyanzi (lisocabtagene maraleucel, liso-cel) as a second-line treatment, compared to the current standard of care, which includes high-dose chemotherapy (HDCT) and hematopoietic...Stem CellsTransplant [HSCT]) for comparison.

In the study, 184 patients with primary refractory LBCL or relapsed disease within ≤12 months after first-line treatment who were eligible for autologous HSCT were randomly assigned to receive Breyanzi (n=92) or salvage chemotherapy followed by high-dose chemotherapy and autologous HSCT (n=92), which is considered the current standard of care for these patients. In this trial, which allowed crossover, 50 patients who failed to achieve remission after 9 weeks (three cycles of salvage chemotherapy) or at any time after disease progression following randomization crossed over from the standard-of-care group to receive Breyanzi.

Data show that the majority of patients (86%) treated with Breyanzi achieved complete or partial remission, and 66% reached complete remission (CR). In contrast, less than half (48%) of patients receiving standard care achieved remission, with only 39% reaching complete remission (p<0.0001). Compared to standard care, the median progression-free survival (PFS) for Breyanzi treatment was significantly longer (14.8 months vs. 5.7 months [HR=0.406; p=0.0001]). Although overall survival (OS) data are not yet mature, a pre-specified interim analysis showed a strong trend toward improvement with Breyanzi compared to standard care (HR=0.509, 95% CI: 0.258-1.004, p=0.0257).

In the study, Breyanzi demonstrated manageable safety, with very low incidence of severe cytokine release syndrome (CRS) and neurologic events (NE), and no new safety signals were observed in the second-line treatment. No grade 4/5 CRS or NE was reported in the study. Any-grade CRS was reported in 49% of patients, with only one patient reporting grade 3 CRS. Among patients treated with Breyanzi, 12% reported any-grade NE, with four patients (4%) reporting grade 3 NE. (Bioon.com)

Source of the original text:Bristol Myers Squibb’s Breyanzi (lisocabtagene maraleucel) Significantly Improves Outcomes, Showing Superiority Over 20-Year Standard of Care in Second-Line Relapsed or Refractory Large B-cell Lymphoma Based on TRANSFORM Study Results