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 ≤12 months after autologous hematopoietic cell transplant [ AHCT ]). Patients received axicabtagene ciloleucel 2x10 6 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 ≥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 ≥3 treatmentrelated adverse events ( AEs ) included neutropenia ( 66 %), leukopenia ( 44 %), anemia ( 43 %), febrile neutropenia ( 31 %), and encephalopathy ( 21 %).

Grade ≥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 .

REFERENCE

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 .