CHICAGO – 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 (axi-cel) when compared to the current standard-of-care chemoimmunotherapy, according to results of the Phase III ZUMA-7 trial reported by researchers from The University of Texas MD Anderson Cancer Center .
Data from the study were presented today by Jason Westin, M.D., director of clinical research in the Department of Lymphoma and Myeloma , at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting and published concurrently in the New England Journal of Medicine .
At a median follow-up of 47.2 months, axi-cel demonstrated a statistically significant improvement in overall survival (OS) over standard therapy. The median OS had not yet been reached for axi-cel, meaning more than half of the patients remained alive at the time of this analysis, compared to a median OS of 31.1 months on the control arm. The estimated four-year survival rate was 54.6% with axi-cel and 46% with standard care, corresponding to a 27.4% reduction in the risk of death with the cell therapy.
“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,” Westin said. “The quality of life for patients treated with axi-cel improved faster than those treated with chemotherapy, and our results support axi-cel as a second-line treatment for these patients.”
B-cell lymphoma is a type of non-Hodgkin lymphoma that originates in the B cells. According to the American Cancer Society, B-cell lymphomas account for approximately 85% of all lymphomas in the U.S. Diffuse large B-cell lymphoma is the most common, with nearly 30,000 people across the country newly diagnosed each year. Axi-cel was approved by the 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.
The international ZUMA-7 trial included 359 patients who were refractory or relapsed within one year of completing first-line therapy. Patients were randomized to receive either axi-cel, 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 axi-cel achieved a median progression-free survival (PFS) of 14.7 months versus 3.7 months with standard therapy, with an estimated four-year PFS rate of 41.8% versus 24.4% with standard therapy. The OS and PFS benefits favoring axi-cel were consistent across all key patient subgroups.
The safety of axi-cel was manageable and consistent with previous trials. In those treated with axi-cel, 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. No new cytokine release syndrome events were recorded.
“On this groundbreaking trial, more patients lived longer with axi-cel compared to the standard treatment. This is the first trial in any cancer type where a CAR T cell therapy improved survival versus 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,” Westin said. “We currently are enrolling patients in a study in first-line therapy, the ZUMA-23 clinical trial, to evaluate axi-cel compared with chemotherapy.”
The trial was funded by Kite Pharma, a Gilead Company. Westin receives research support and served on the advisory board and as a consultant for Kite Pharma. A full list of co-authors and their disclosures may be found here .
New England Journal of Medicine