Breyanzi shows superiority over 20-year standard of care in second-line r/r large B-cell lymphoma based on TRANSFORM study results.
Results show, at a median follow up of 6.2 months, Breyanzi significantly improved event-free survival (EFS) compared to standard of care, the study’s primary endpoint, with a median EFS of 10.1 months (95% CI: 6.1-NR) for Breyanzi and 2.3 months (95% CI: 2.2-4.3) for standard of care (HR: 0.349; p<0.0001), representing a 65% reduction in risk of efs events with breyanzi. the data will be presented in an oral session during the 63rd american society of hematology (ash) annual meeting and exposition (abstract #91) and has been selected for inclusion in the ash annual meeting press program.
“For more than 20 years, salvage chemotherapy followed by high-dose chemotherapy and stem cell transplant have been the mainstay of care for patients with second-line relapsed or refractory LBCL, but only a small portion of patients experience long-term benefit with this approach,” said Manali Kamdar, M.D., lead investigator and Associate Professor, Clinical Director of Lymphoma Services, Division of Hematology, Hematologic Malignancies and Stem Cell Transplantation, University of Colorado Cancer Center. “With liso-cel outperforming the current standard of care for patients with hard-to-treat disease in the TRANSFORM study, these results may pave the way for a practice-changing treatment approach where patients whose disease relapses or is refractory to frontline therapy can be treated with a personalized CAR T cell therapy to increase the potential for improved outcomes.”
In the TRANSFORM study ; 184 patients with primary refractory LBCL or relapsed disease within greater than 12 months after first-line therapy who were eligible for autologous HSCT were randomized 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 the trial, which allowed for crossover, 50 patients switched from the standard of care arm to receive Breyanzi following failure to achieve a response by nine weeks post-randomization (after three cycles of salvage chemotherapy) or after disease progression at any time. The majority of patients (86%) treated with Breyanzi achieved a complete or partial response, with 66% of patients achieving a complete response. In comparison, less than half (48%) of patients who received the standard of care achieved a response, and only 39% of these patients achieved a complete response (p<0.0001). median progression-free survival was significantly longer with breyanzi compared to standard of care (14.8 months vs. 5.7 months [hr: 0.406; p="0.0001])." although overall survival data were not yet mature, the prespecified interim analysis showed a trend favoring breyanzi compared with the standard of care (hr: 0.509, 95% ci: 0.258-1.004, p="0.0257)."
Breyanzi exhibited a manageable safety profile with very low rates of severe cytokine release syndrome (CRS) and neurologic events, and no new safety signals were observed in this second-line setting. In the trial, no Grade 4/5 CRS or neurologic events were reported. Any-grade CRS was reported in 49% of patients, with Grade 3 CRS reported in only one patient. Any-grade neurologic events were reported in 12% of patients treated with Breyanzi, with Grade 3 neurologic events reported in four patients (4%).
Breyanzi is approved by the FDA for the treatment of adult patients with relapsed or refractory LBCL after two or more lines of systemic therapy, 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. Breyanzi is not indicated for the treatment of patients with primary central nervous system lymphoma.
About TRANSFORM : TRANSFORM (NCT03575351) is a pivotal, global, randomized, multicenter Phase III trial evaluating Breyanzi compared to current standard of care regimens in adults with high-risk, transplant-eligible, relapsed and refractory large B-cell lymphoma (LBCL). All enrolled patients have LBCL and were relapsed or refractory within less than 12 months from CD20 antibody and anthracycline containing first-line therapy. Patients were randomized to receive Breyanzi or standard of care salvage therapy, including rituximab plus dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP), rituximab plus ifosfamide, carboplatin and etoposide (R-ICE), or rituximab plus gemcitabine, dexamethasone and cisplatin (R-GDP) per the investigators’ choice before proceeding to high-dose chemotherapy and hematopoietic stem cell transplant. The primary endpoint of the study is event-free survival, defined as time from randomization to death from any cause, progressive disease, failure to achieve complete response or partial response, or start of new antineoplastic therapy due to efficacy concerns, whichever occurs first. Complete response rate is a key secondary endpoint. Other efficacy endpoints include progression-free survival, overall survival, overall response rate and duration of response.
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