Yescarta CAR T-Cell therapy demonstrates significantly longer overall survival versus standard of care as initial treatment of relapsed/refractory large B-cell Lymphoma

Yescarta is the first treatment in nearly 30 years to demonstrate a significant improvement in survival in this patient population. The late-breaking data are being presented orally at the 2023 American Society of Clinical Oncology Annual Meeting (Abstract #LBA107) and published simultaneously in the New England Journal of Medicine.

With a median follow-up of 4 years (47.2 months), a one-time treatment with Yescarta demonstrated significantly longer overall survival (hazard ratio [HR] 0.726; 95% CI: 0.540-0.977, stratified one-sided log rank p-value = 0.0168) compared to SOC with a 27.4% reduction in the risk of death, which corresponds to a 38% relative improvement in overall survival, for patients with R/R LBCL within 12 months completion of first-line therapy.

SOC therapy for this patient population has historically been a multi-step process expected to end with stem-cell transplant. The process starts with chemoimmunotherapy, and if a patient responds and can tolerate further treatment, they move on to high-dose chemotherapy (HDT), followed by stem cell transplant (ASCT). It is notable that despite this process being the historical SOC, less than 40% of patients were able to make it through to complete their stem cell transplant compared with 94% of patients in the ZUMA-7 study who received Yescarta CAR T-cell therapy.

“As the first treatment in nearly three decades to significantly improve survival for patients with relapsed/refractory large B-cell lymphoma, axi-cel can potentially change the standard of care for these patients who previously had very limited options for successful curative therapy,” said Jason Westin, MD, MS, FACP, ZUMA-7 Principal Investigator, Director, Lymphoma Clinical Research, and Associate Professor, Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center. “The totality of the ZUMA-7 data provides a compelling case for axi-cel to be used as soon as patients with large B-cell lymphoma do not respond to or relapse from first-line treatment.”

The primary OS analysis, conducted per protocol five years after the first subject was randomized, demonstrated superior OS with Yescarta over the SOC arm, despite more than half (57%) of patients in the SOC arm subsequently receiving cellular immunotherapy off protocol; of these, 77% of patients received Yescarta. Median OS was longer with Yescarta versus SOC (not reached versus 31.1 months, respectively) and 48-month OS estimates were higher with Yescarta (54.6% versus 46.0%, respectively). Yescarta’s OS benefit versus SOC was also similar across key patient subgroups, including patients with high-risk features, such as those with primary refractory disease, high-grade B-cell lymphoma (including double-hit lymphomas) and aged 65 and above. Progression-free survival (PFS) by investigator review confirmed the benefit of Yescarta over SOC (HR 0.506; 95% CI: 0.383-0.669), with 48-month PFS estimates of 41.8% with Yescarta versus 24.4% with SOC.

Yescarta’s safety profile remains consistent with prior studies, and no new treatment-related deaths occurred since the primary EFS analysis. The primary EFS analysis showed that Grade 3 or higher adverse events (AEs) occurred in 91% of patients treated with axi-cel compared with 83% of those treated with SOC. The most common grade 3 or higher AEs were neutropenia (69% vs 41%, respectively), anemia (30% vs 39%), and leukopenia (29% vs 22%).

“Overall survival is the gold standard in cancer treatment and confirms Yescarta’s place as a treatment of curative intent for patients with relapsed/refractory large B-cell lymphoma,” said Frank Neumann, MD, PhD, SVP, Kite’s Global Head of Clinical Development. “Kite shares this momentous achievement with all of the patients and researchers who participated in the ZUMA-7 study since the first patient was randomized five years ago.”

See- " Survival with Axicabtagene Ciloleucel in Large B-Cell Lymphoma": Jason R. Westin, M.D., Olalekan O. Oluwole, M.D., Marie José Kersten, M.D., Ph.D., et al., for the ZUMA-7 Investigators and Kite Members:June 5, 2023 DOI: 10.1056/NEJMoa2301665.