The use of anti-CD19 chimeric antigen receptor (CAR) T cells (KTE-C19) induced a nearly sixfold higher rate of complete response compared with historical outcomes in patients with refractory, aggressive non-Hodgkin lymphoma (NHL), according to results from the phase II ZUMA-1 trial (abstract LBA-6) presented at the 58th American Society of Hematology Annual Meeting and Exposition, held December 3–6 in San Diego, California.
The study, presented by Sattva S. Neelapu, MD, of the University of Texas MD Anderson Cancer Center in Houston, is the first multicenter trial of this cellular immunotherapy-based treatment approach for lymphoma.
“Patients with aggressive NHL have a major unmet need in terms of available therapies that can induce long-term remission, and there really has been no new treatment for these patients for over 20 years,” said Dr. Neelapu, in a press release. “KTE-C19 could potentially be the solution to that need, and the hope is that this treatment option could be curative for some of these patients.”
According to the study abstract, patients with refractory aggressive NHL have historically had a complete response rate of about 8% and a partial response rate of about 18%. Phase I of the ZUMA-1 trial was conducted at four institutions and showed a complete remission rate of 43% at 12 months. Phase II of the study was designed to test whether KTE-C19 would be feasible in a real-world setting, and expanded it to include 22 institutions.
This phase II study included two cohorts based on tumor type: diffuse large B-cell lymphoma (DLBCL; cohort 1) and primary mediastinal B-cell lymphoma or transformed follicular lymphoma (cohort 2). Patients received a target dose of 2 × 106 anti-CD19 CAR T cells/kg after a low-dose conditioning regimen of cyclophosphamide and fludarabine daily for 3 days. The primary endpoint was objective response rate. Patients were required to have received a prior anti-CD20 antibody and an anthracycline-containing regimen. Dr. Neelapu presented results from 51 patients in cohort 1 who were eligible for analysis.
The overall response rate for cohort 1 was 76%, with 47% of patients achieving complete remission and 29% of patients achieving partial remission. Most responses to KTE-C19 were noted within the first month. As has been noted in previous studies, some patients’ cancers recurred after the first few months. By the end of month 3, the overall remission rate was 39%.
Serious adverse events related to KTE-C19 that were reported in the total DLBCL cohort of 73 patients included neurologic events (25%; typically temporary confusion or disorientation) and grade 3 or higher cytokine release syndrome (14%). The most common symptoms of cytokine release syndrome were fever, drop in blood pressure, and shortness of breath, according to Dr. Neelapu. Researchers report one patient died as a result of over-activation of the immune system.
The researchers said the results are encouraging from an efficacy standpoint and also show that CAR T-cell manufacturing, treatment logistics, and the management of adverse events can be successfully implemented across multiple sites.
“Efficacy often tends to be lower when you apply a new treatment at multiple centers,” said Neelapu. “It was very gratifying to see that efficacy and side effects are similar to what was observed in previous single-institution studies.”