The ZUMA-1 Phase 2 clinical trial of the CAR T-cell therapy axicabtagene ciloleucel (KTE-C19) showed that 82% of patients with treatment-resistant or relapsed aggressive non-Hodgkin’s lymphoma (NHL) responded to the cell therapy — a response independent of disease type, stage, or characteristics.
Among those patients, 54% had a complete clearance of their cancer, the European Hematology Association (EHA) reported.
The data were presented at the 22nd Congress of EHA June 22-25 in Madrid, Spain, where Yi Lin, MD, PhD, from the Mayo Clinic in Minnesota presented the study, “Clinical and Biologic Covariates of Outcomes In ZUMA-1: A Pivotal Trial of Axicabtagene Ciloleucel (Axi-Cel; Kte-C19) in Patients With Refractory Aggressive Non-Hodgkin Lymphoma (NHL).”
ZUMA-1 recruited 101 patients with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL), who were treated with the CAR T-cell therapy. The majority, or 85%, had stage 3 or 4 of the disease, and nearly half had an International Prognostic Index (IPI) of 3 or 4, indicating a very poor prognosis.
Importantly, the response rate of 82% did not differ in people with different disease subtypes, refractory status, lymphoma stage, or IPI score.
Patients had been followed for a median of 8.7 months at the time of analysis. At that point, 44% had an ongoing response and 39% were in complete remission. The median duration of response was 8.2 months in the entire group, but had not been reached among patients who had a complete response.
At the time of analysis, the median overall survival had not been reached. At six months, 80% of the treated patients were still alive.
The treatment’s developer, Kite Pharma, first disclosed positive data from the trial in late February of this year, and announced in April at the American Association of Cancer Research 2017 Annual Meeting that the trial met its primary endpoint.
The current presentation underscored that the rate of complete responses was seven times higher compared to controls in earlier studies.
The most common side effects of the treatment were a lowering of blood cell counts. Researchers noted more severe cytokine release syndrome in 13% of participants, and neurologic events occurred in 28%. Researchers reported that all of the events were resolved with the exception of one mild memory impairment.
But 21% of patients also experienced impacts on their brain, and on May 8, Kite reported that a patient in the trial had died of brain swelling. Four additional patients have died during the trial, but not all deaths were related to the treatment.
The safety profile of KTE-C19 is, nevertheless, judged manageable in these patients, who lack other options to treat their aggressive disease.
On May 26, the U.S. Food and Drug Administration (FDA) accepted Kite’s biologics license application (BLA) of KTE-C19 for the treatment of refractory aggressive non-Hodgkin’s lymphoma. The application has been granted priority review, and the FDA set an action date of Nov. 29 at the latest.