At the 2017 AACR Annual Meeting, Frederick L. Locke, MD, from the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Florida, and co-authors presented updated results from the primary analysis of ZUMA-1, in which treatment with KTE-C19 (now called axicabtagene ciloleucel) continued to demonstrate high objective response rates (ORR).
Adult patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma were included in the study. Participants were required to have an Eastern Cooperative Oncology Group performance status score of 0-1 and refractory disease (defined as progressive or stable disease as best response to last prior therapy, or relapse â‰¤12 months after autologous hematopoietic cell transplant [AHCT]). Patients received axicabtagene ciloleucel 2×106 cells/kg after conditioning with low-dose cytarabine and fludarabine.
As of January 27, 2017, the study had enrolled 111 patients (median age = 58 years; range = 23-76 years) from 22 institutions, 101 of whom (91%) received axicabtagene ciloleucel. Most were male (67%) and had stage III/IV disease (85%).
Sixty-nine percent of the patient population received at least three prior lines of therapy. Most (79%) were refractory to chemotherapy and had not received AHCT, whereas 21 percent had received AHCT but relapsed within 12 months. Axicabtagene ciloleucel was successfully manufactured in 110 patients (99%), with an average turnaround time from apheresis to the clinical site of 17 days.
After a median follow-up of 8.7 months, 82 percent of patients (n=101) responded to treatment with axicabtagene ciloleucel, including 54 percent who achieved complete response (CR) and 28 percent who achieved partial response (PR).
Response was consistent across key covariates, including disease subtype, refractory status, stage, and International Prognostic Index score, according to the researchers. For example, patients who were refractory to â‰¥2 lines of therapy had an ORR of 83 percent and those who relapsed within one year following AHCT had an ORR of 76 percent.
The median duration of response in the overall population was 8.2 months but was not reached for patients who achieved CR. Median overall survival was not reached, and 80 percent of patients remained alive at six months.
"The CR rate was seven-fold higher compared to historical controls, and nearly half the patients have an ongoing response," Dr. Locke and co-authors concluded.
At the time of data presentation, 44 percent of patients were still receiving treatment. The most common grade â‰¥3 treatment-related adverse events (AEs) included neutropenia (66%), leukopenia (44%), anemia (43%), febrile neutropenia (31%), and encephalopathy (21%).
Grade â‰¥3 cytokine release syndrome (CRS) and neurologic events (NEs) occurred in 13 percent and 28 percent of patients, respectively, all of which resolved except for one grade 1 memory impairment. Notably, the rates of these events (the greatest concerns with chimeric antigen receptor T-cell therapies) were higher in the interim analysis (18% and 34%, respectively) than after this longer-term follow-up. "We believe the rates of CRS and NEs decreased over the course of the study as clinicians gained experience in the management of AEs," Dr. Locke noted during his presentation.
The study's findings are limited by the short duration of follow-up and single arm design. Based on results from this trial, the manufacturers of axicabtagene ciloleucel submitted a biologics license application to the U.S. Food and Drug Administration for the treatment of patients with aggressive non-Hodgkin lymphoma who are ineligible for AHCT.
Locke FL, Neelapu SS, Bartlett NL, et al. Primary results from ZUMA-1: a pivotal trial of axicabtagene ciloleucel (axicel; KTE-C19) in patients with refractory aggressive non-Hodgkin lymphoma (NHL). CT019. Presented at the 2017 AACR Annual Meeting, April 5, 2017; Washington, DC.