KTE-X19 induces durable CRs, MRD negativity in ALL
SAN DIEGO—An update of the ZUMA-3 trial showed that KTE-X19—an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy—can induce high rates of undetectable minimal residual disease (MRD) and durable complete remissions (CRs) in adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).
And this was particularly the case at the middle dose level of 1 x 106 cells/kg.
William G. Wierda, MD, PhD, of The University of Texas MD Anderson Cancer Center in Houston, presented the update at the 2018 ASH Annual Meeting (abstract 897*).
Dr. Wierda explained that KTE-X19 is a new name for KTE-C19, also known as axicabtagene ciloleucel (Yescarta™), which is currently approved in the United States for the treatment of relapsed diffuse large B-cell lymphoma in adults and in Europe for diffuse large B-cell lymphoma and primary mediastinal large B-cell lymphoma.
“This approval was based on the ZUMA-1 clinical trial,” he said, “which showed a 54% complete remission rate and 82% overall response rate with durable remissions.”
ZUMA-3 (NCT02614066) is a phase 1/2 study of KTE-X19—a CAR T cell with CD3ζ signaling and CD28 costimulatory domains—for relapsed or refractory adults with ALL.
Dr. Wierda presented the phase 1 data available at the cutoff of August 16.
Study design
Patients underwent leukapheresis to collect their T cells for production and received bridging therapy selected by the treating physician from several prespecified regimens to maintain disease control.
Conditioning chemotherapy included fludarabine at 25 mg/m2 on days -4, -3, and -2 and cyclophosphamide at 900 mg/m2 on day -2.
Patients received KTE-X19 on day 0. They were monitored and released from the hospital on day 7 or upon resolution of any toxicities.
The investigators assessed response, including bone marrow evaluation, on day 28, week 8, month 3, and every 3 months for the first year as well as every 6 months for the second year of follow-up.
The dose-finding portion of the trial initially enrolled three patients. They received a dose of 2 x 106 CAR T cells/kg and were monitored for dose-limiting toxicities (DLTs).
If there were no DLTs in the first three patients, phase 2 could open or investigators could further expand the 2 x 106 dose level or explore lower doses of the product (1 x 106 cells/kg and 0.5 x 106 cells/kg).
Investigators defined DLTs as:
- KTE-X19-related events in the first 28 days, including grade 4 hematologic toxicity lasting more than 30 days and not attributable to ALL
- Grade 3 nonhematologic toxicities lasting more than 7 days
- Grade 4 nonhematologic toxicities regardless of duration, excluding grade 4 cytokine release syndrome (CRS) events lasting 7 days or less
- Neurologic events that resolve to grade 1 in 2 weeks or to baseline within 4 weeks.
Dr. Wierda said no DLTs occurred among the first 3 patients treated, and all dose levels were explored in phase 1.
Patients
As of the cutoff date, 54 patients were enrolled, confirmed eligible, and underwent leukapheresis. Six patients did not receive conditioning, three patients received conditioning but not KTE-X19, and one patient withdrew from the study after the first failed production of CAR T cells.
So 44 patients received KTE-X19. Six patients received the highest dose of CAR T cells (2 x 106/kg), 22 received the middle dose (1 x 106/kg), and 16 received the lowest dose (0.5 x 106/kg).
The patients’ median age was 46 (range, 18 – 77). Almost half (48%) were male, and 68% had three or more prior treatment regimens. Forty-one percent had prior blinatumomab, and 14% had prior inotuzumab.
