Patients with early relapsed or refractory large B-cell lymphoma had significantly improved overall survival when treated with the chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel when compared to the current standard-of-care chemoimmunotherapy, according to results of the phase III ZUMA-7 trial. These findings were presented by Jason Westin, MD, Director of Clinical Research in the Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center, at the 2023 ASCO Annual Meeting (Abstract LBA107) and published concurrently in The New England Journal of Medicine.
At a median follow-up of 47.2 months, axicabtagene ciloleucel demonstrated a statistically significant improvement in overall survival over standard therapy. The median overall survival had not yet been reached for patients treated with axicabtagene ciloleucel compared to a median overall survival of 31.1 months for those on the control arm. The estimated 4-year survival rate was 54.6% with axicabtagene ciloleucel and 46% with the standard of care, corresponding to a 27.4% reduction in the risk of death.
Jason Westin, MD
“This is the first randomized phase III trial in nearly 30 years to improve overall survival with second-line curative therapy for patients with aggressive lymphoma. High-dose chemotherapy and stem cell transplant—the old standard—cured a small portion of patients, but resulted in side effects for all,” Dr. Westin explained. “The quality of life for patients treated with axicabtagene ciloleucel improved faster than those treated with chemotherapy, and our results support axicabtagene ciloleucel as a second-line treatment for these patients.”
Axicabtagene ciloleucel was approved by the U.S. Food and Drug Administration in 2017 for the treatment of specific patients with B-cell lymphomas, and ongoing studies continue to evaluate the benefits of this therapy relative to current standard approaches.
More About ZUMA-7
The international ZUMA-7 trial included 359 patients with refractory or relapsed large B-cell lymphoma within 1 year of completing first-line therapy. Patients were randomly assigned to receive either axicabtagene ciloleucel, an autologous anti-CD19 CAR T-cell therapy, or standard of care, which consists of two to three cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem cell transplantation in responding patients.
Patients receiving axicabtagene ciloleucel achieved a median progression-free survival of 14.7 months vs 3.7 months with standard therapy, with an estimated 4-year progression-free survival rate of 41.8% vs 24.4% with standard therapy. The overall survival and progression-free survival benefits favoring axicabtagene ciloleucel were consistent across all key patient subgroups.
The safety of axicabtagene ciloleucel was manageable and consistent with previous trials. In those treated with axicabtagene ciloleucel, grade 3 cytokine-release syndrome occurred in 6% of patients and grade 3 or higher neurologic events occurred in 21% of patients, as reported in the primary event-free survival analysis published in The New England Journal of Medicine. No new cytokine-release syndrome events were recorded.
“On this groundbreaking trial, more patients lived longer with axicabtagene ciloleucel compared to the standard treatment. This is the first trial in any cancer type where a CAR T-cell therapy improved survival vs older chemotherapy. This is an incredible breakthrough, but we continue to work to learn where else CAR T-cell therapy can prove to be superior in treating patients with high-risk B-cell lymphoma,” Dr. Westin said.
He added, “We currently are enrolling patients in a study in first-line therapy, the ZUMA-23 clinical trial, to evaluate axicabtagene ciloleucel compared with chemotherapy.”
Disclosure: The trial was funded by Kite Pharma, a Gilead Company. For full disclosures of the study authors, visit coi.asco.org.
