As reported in The Lancet Oncology by Caron A. Jacobson, MD, and colleagues, the phase II ZUMA-5 trial showed that axicabtagene ciloleucel, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, produced high rates of durable responses in patients with relapsed or refractory indolent non-Hodgkin lymphoma.
The study supported the March 2021 accelerated approval of the agent for the treatment of adult patients with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy.
Caron A. Jacobson, MD
Study Details
The trial enrolled 153 patients with follicular lymphoma or marginal zone lymphoma who had received two or more lines of prior therapy (including an anti-CD20 monoclonal antibody with an alkylating agent) from sites in the United States and France between June 2017 and July 2020.
Patients underwent leukapheresis and received conditioning chemotherapy with cyclophosphamide at 500 mg/m² per day and fludarabine at 30 mg/m² per day on days −5, −4, and −3, followed by a single infusion of axicabtagene ciloleucel at 2 × 106 CAR T cells per kg on day 0.
The primary endpoint was overall response rate (complete or partial response) on independent review committee assessment using Lugano classification.
Responses
Axicabtagene ciloleucel was successfully manufactured for all enrolled patients. As of data cutoff (September 2020), 148 patients had received an infusion, including 124 (84%) with follicular lymphoma and 24 (16%) with marginal zone lymphoma.
Median follow-up for the primary analysis was 17.5 months (interquartile range = 14.1–22.6 months). Among 104 patients eligible for the primary analysis (84 with follicular lymphoma and 20 with marginal zone lymphoma), overall response was observed in 96 (92%, 95% confidence interval [CI] = 85%–97%), with complete response in 77 (74%). Overall response was observed in 79 patients (94%, 95% CI = 87%–98%) with follicular lymphoma, with complete response in 66 (79%), and in 17 patients (85%, 95% CI = 62%–97%) with marginal zone lymphoma, including complete response in 11 (55%).
In an updated analysis (data cutoff September 2020), with a median follow-up of 23.3 months, overall response was achieved in 100 (92%) of 109 eligible patients, including 81 (94%) of 86 with follicular lymphoma and 19 (83%) of 23 with marginal zone lymphoma. In this population, median duration of response was not reached among all responders, not reached in responders with follicular lymphoma, and 11.1 months (95% CI = 8.1 month–not estimable) in responders with marginal zone lymphoma. At 18 months, the estimated proportion of patients remaining in response was 65.6%.
Adverse Events
Among the 148 patients who received axicabtagene ciloleucel infusion by data cutoff, grade ≥ 3 adverse events occurred in 86%, with the most common being cytopenias (70%) and infections (18%). Cytokine-release syndrome of any grade occurred in 82% of patients and was grade ≥ 3 in 7%. Neurologic adverse events of any grade occurred in 59% and were grade ≥ 3 in 19%. Serious adverse events occurred in 50% of patients. Death due to adverse events occurred in four patients (3%), with one death (due to multisystem organ failure) considered related to treatment.
The investigators concluded, “Axicabtagene ciloleucel showed high rates of durable responses and had a manageable safety profile in patients with relapsed or refractory indolent non-Hodgkin lymphoma.”
Dr. Jacobson, of the Department of Medical Oncology, Dana-Farber Cancer Institute, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Kite, a Gilead Company. For full disclosures of the study authors, visit thelancet.com.
