KTE-X19 induces durable CRs, MRD negativity in ALL
Patients had a median bone marrow blast percentage of 59% (n=44; range, 5% - 100%) at screening and 70% (n=40; range, 0 – 97%) prior to conditioning but after bridging therapy.
The safety analysis included all 44 treated patients, and the efficacy analysis included 36 patients.
“[T]he follow-up period was too short from dosing for the most recently treated eight patients,” Dr Wierda explained.
The median follow-up was 15.1 months for the 36 efficacy-evaluable patients.
Safety
All patients had a treatment-emergent adverse events (TEAEs), with 75% having grade 3/4 events.
Grade 5 TEAEs included three due to progressive disease, three due to infections, and one stroke 6 weeks after infusion.
Two patients died of KTE-X19-related AEs. One patient in the 2 x 106 dose group had multiorgan failure secondary to CRS on study day 6. The other patient, in the 0.5 x 106 dose group, had a stroke after infusion in the context of CRS and neurologic events (NEs) on day 7.
Investigators detected a higher incidence of grade 3 and greater CRS for the six patients treated at the highest dose. Half developed CRS of grade 3 or higher, compared with 18% in the 1 x 106 dose cohort and 19% in the 0.5 x 106 dose cohort.
Grade 3 or higher NEs were more common than CRS. The lowest incidence occurred in the lowest dose cohort, at 25%, compared with 45% in the 1 x 106 dose cohort and 50% in the 2 x 106 dose cohort.
Due to the incidence of grade 3 and greater NEs observed in the 1 x 106 dose cohort, investigators revised the management guidelines for AEs. The revisions included using tocilizumab only for CRS—and not for NEs—and initiating steroids for grade 2 NEs instead of waiting for grade 3.
Eight patients were treated under the revised recommendations, and the incidence of grade 3 NEs was 13%, with no grade 4 or 5 NEs.
“This compared favorably with the 14 patients treated at the same dose level but prior to these changes," Dr. Wierda said.
In comparison, 57% developed grade 3 NEs and 7% grade 4 with the original AE management protocol.
The incidence of grade 3 CRS remained low, with no CRS events of grade 4 or greater with the revised recommendations.
Efficacy
The best overall response in the 36 efficacy-evaluable patients was 69% CR and CR with incomplete hematologic recovery (CRi).
Seventy-five percent of these patients had undetectable MRD in the bone marrow at 10-4 sensitivity at 3 months of follow-up.
All patients in the 1 x 106 dose cohort (n=14) responded. Ninety-three percent achieved a CR/CRi, 7% had a partial response, and all had undetectable MRD in the bone marrow.
The median duration of response was 12.9 months in the 1 x 106 cohort. This was the dose selected for the phase 2 trial, which is now enrolling patients.
ZUMA-3 was sponsored by Kite, a Gilead Company.
Dr. Wierda disclosed research funding from AbbVie and Genentech.
* Data in the abstract differ from the presentation.
