Promising CAR T-Cell Agent for ALL Enters Phase II With Revised AE Management Protocol

CHICAGO-A phase I study of an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy (KTE-X19) showed success in refining cell dosing and adverse event management protocols in patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL). The results of the interim analysis (abstract 7006), which found that 72% of patients achieved a complete remission (CR) or CR with incomplete bone marrow recovery (CRi), were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 31–June 4 in Chicago.

A pivotal phase II study is ongoing, using a dose of 1×10⁶ KTE-X19 cells/kg and the revised adverse event management protocol developed in the phase I study.

KTE-X19 is an autologous anti-CD19 CAR T-cell therapy that is produced with a modified process designed to remove circulating tumor cells. The novel manufacturing technique, which involves leukapheresis, is interesting, but “it remains to be seen what will be the result in terms of differentiating this agent from the other ones,” Gail Roboz, MD, professor of medicine and director of the leukemia program at Weill Cornell Medicine, who moderated the session, told Cancer Network.

The therapy also faces the same standard concerns as CAR T-cell therapy, specifically that patients may suffer during the manufacturing delay. “The patients are sitting around getting worse and worse with more and more resistant therapy, while we're waiting, and that is very hard,” said Roboz.

The study population included 45 adults with R/R B-cell ALL; of these, > 5% had bone marrow blasts, and Eastern Cooperative Oncology Group performance scores ranged from 0 to 1. Patients received KTE-X19 doses of 0.5, 1, or 2×10⁶ cells/kg following conditioning chemotherapy (n = 6, n = 23, and n = 16, respectively). Additional patients in a 1×10⁶ dose cohort received revised adverse event management protocol, in which corticosteroids were administered at onset of grade ≥ 2 neurologic events (NEs), while tocilizumab was reserved for active toxicity.

The median participant age was 46 years (49% male). A total of 67% had undergone at least three prior therapies, and the median precondition bone marrow blasts was 70%. The median follow-up was 16 months. Grade 3 or higher adverse events in the patients who received doses of 2×10⁶, 1×10⁶, and 0.5×10⁶, respectively, included hypotension (50%, 39%, 19%), pyrexia (50%, 39%, 31%) and encephalopathy (33%, 26%, 13%). Two KTE-X19-related grade 5 adverse events–cerebral infarction and multi-organ failure–occurred in the context of cytokine release syndrome (CRS).

In total, 29% of patients had a grade 3 or higher CRS, and 38% had a grade 3 or higher neurologic event; 41 patients were followed for at least 2 months, and 68% of these had a CR or CRi. Of 19 patients treated with the 1×10⁶ dose and followed for at least 2 months, 84% had a CR/CRi, with a median event-free survival of 12.9 months, and 9 patients were treated with 1×10⁶ dosing and revised adverse event management. In this group, 2 patients (22%) had grade 3 CRS, and 1 (11%) had a grade 3 neurologic event. There were no grade 4 or 5 CRS or neurologic events.