For patients with chemo-refractory, aggressive non-Hodgkin lymphoma (NHL), treatment with anti-CD19 chimeric antigen receptor (CAR) T-cell therapy (known as KTE-C19) induced a CR rate that was nearly six times higher than what has typically been seen historically, according to results from the phase II ZUMA-1 trial, the first multicenter trial of this immunotherapy-based approach in patients with aggressive NHL.
The study was conducted at 22 institutions and enrolled 111 patients into two cohorts: those with diffuse large B-cell lymphoma (DLBCL) and those with primary mediastinal B-cell lymphoma or transformed follicular lymphoma. Sattva S. Neelapu, MD, from the MD Anderson Cancer Center at the University of Texas in Houston, presented the results of an interim analysis of patients with DLBCL.
At the time of data presentation, 51 patients (median age = 58 years; range = 25-76 years) were eligible for analysis; 78 percent were refractory to two or more previous lines of therapy, 20 percent had relapsed within 12 months after AHCT, and 61 percent were treated with three or more lines of prior therapy.
The overall response rate (ORR; the study's primary endpoint) was 76 percent, which compared favorably with the historical control assumption of 20 percent (p<0.001), Dr. Neelapu reported. The rates of CRs and PRs were 47 percent and 29 percent, respectively.
Nearly all of these responses (92%) occurred rapidly, within the first month of treatment, and 39 percent of patients had ongoing responses at three months.
"Several patients have continued treatment for months, and [some] patients are experiencing complete remissions lasting one year or longer," Dr. Neelapu told ASH Clinical News. "KTE-C19 was also tested previously in single-institution trials, which found that [some] patients who achieved a complete remission can have ongoing remissions nearly four years later."
The most common grade â‰¥3 treatment-emergent AEs were neutropenia (67%), anemia (39%), thrombocytopenia (29%), febrile neutropenia (27%), and encephalopathy (24%). The two most common side effects of KTE-C19 were cytokine release syndrome (CRS) and neurologic events, which occurred in 20 percent and 29 percent of patients, respectively. "The majority of patients had grade 1 and grade 2 CRS," Dr. Neelapu said. "We found only 13 percent of these patients developed grade â‰¥3 CRS." He added that "neurologic side effects were reversible in the majority of the patients."
"While this product appears to induce a high ORR, there is still room to improve the CR rates in these patients," he added. The researchers are conducting additional biomarker analyses to understand the main drivers for neurologic AEs and CRS, as well as why some patients relapse after achieving a CR or PR. Response duration is still being assessed.
Neelapu SS, Locke FL, Bartlett N, et al. Kte-C19 (anti-CD19 CAR T cells) induces complete remissions in patients with refractory diffuse large B-cell lymphoma (DLBCL): results from the pivotal phase 2 ZUMA-1. Abstract LBA-6. Presented at the 2016 ASH Annual Meeting, December 6, 2016; San Diego, California.