CAR-T shows ‘remarkable’ efficacy as first-line therapy for large B-cell lymphoma
Click Here to Manage Email Alerts
First-line therapy with axicabtagene ciloleucel induced objective responses in 89% of patients with high-risk large B-cell lymphoma, according to phase 2 study results.
An estimated 91% of patients treated with a single infusion of the chimeric antigen receptor T-cell therapy remained alive at 12 months, a primary analysis of the ZUMA-12 trial showed.
Background
The FDA approved axicabtagene ciloleucel (Yescarta, Kite Pharma/Gilead) — often called axi-cel — for adults with relapsed or refractory large B-cell lymphoma after two or more lines of therapy, or for those who are refractory to first-line chemoimmunotherapy or who experienced disease relapse within 12 months of initial treatment.
ZUMA-12 is the first clinical trial to evaluate axi-cel as first-line therapy for patients with high-risk disease, including those with double- or triple-hit lymphoma or patients with high-risk lymphoma as determined by International Prognostication Index scoring.
Nearly half the patients in the study experienced disease progression despite the use of at least two rounds of standard front-line chemotherapy, according to Sattva S. Neelapu, MD, professor and deputy chair of the department of lymphoma/myeloma in the division of cancer medicine at The University of Texas MD Anderson Cancer Center.
ZUMA-12 enrollees were the “highest of the high-risk” patients, Neelapu said.
“Historically, these patients have not done well with standard salvage chemo-immunotherapy or [hematopoietic] stem cell transplant, with an overall survival of less than 10%,” he told Healio.
“Our primary analysis of ZUMA-12 shows extremely high efficacy for axi-cel as first-line therapy in terms of overall response rate,” Neelapu added. “The complete response rate seen in this study thus far is remarkable.”
Methodology
ZUMA-12 enrolled 42 patients with high-risk large B-cell lymphoma, 40 of whom (median age, 61 years; range, 23–86; 68% male) received axi-cel treatment.
Patients received lymphodepleting chemotherapy with fludarabine and cyclophosphamide, followed by an infusion of axi-cel at a dose of 2 × 106 CAR T cells/kg.
The primary efficacy analysis included data from 37 patients.
Median follow-up was 15.9 months, with a data cutoff of May 17, 2021.
Key findings
Results showed an objective response rate of 89% (95% CI, 75-97), with a complete response rate of 78% (95% CI, 62-90).
Median duration of response, EFS and PFS had not been reached.
Three patients (8%) developed grade 3 or greater cytokine release syndrome. Nine patients (23%) experienced grade 3 or greater treatment-related neurotoxicity. No treatment-related grade 5 events occurred.
Clinical implications
"These results are highly encouraging because there is a large unmet need for more effective front-line therapy in patients with high-risk disease,” Neelapu told Healio. “Previous studies using more intense chemotherapy or [hematopoietic] stem cell transplantation as frontline consolidation therapy has done little to improve outcomes for patients.”
These results confirm the need for further investigation, Neelapu said. He predicted that first-line axi-cel will perform better than standard front-line chemotherapy among high-risk patients.
“This study — at least compared with historical data in this population — looks far superior in terms of durability outcomes to date,” he said. “The results warrant additional randomized study of axi-cel head-to-head with chemoimmunotherapy.”
For more information:
Sattva S. Neelapu, MD, can be reached at sneelapu@mdanderson.org.
Collapse
Click Here to Manage Email Alerts