Blinatumomab shows promise in relapsed, refractory ALL

CHICAGO — Blinatumomab appeared safe and effective in adults with relapsed or refractory B-precursor acute lymphoblastic leukemia, according to results of a phase 2 study presented at the ASCO Annual Meeting.

Max S. Topp, MD, of the University Hospital of Würzburg in Germany, and colleagues sought to evaluate blinatumomab (MT103, Micromet) — a bispecific T-cell engaging (BiTE) antibody that activates T cells to target CD19 — in 189 patients with Philadelphia chromosome-negative ALL.

All patients had refractory disease or had relapsed within 12 months of the primary diagnosis or allogeneic stem cell transplantation. The median age of patients was 39 years (range, 18-79).

“CD19 is a very good target in the disease setting of ALL as the vast majority of ALL cells will express CD19 during primary diagnosis, as well as during relapsed or refractory disease,” Topp said during a presentation. “We have conducted an exploratory phase 2 study of blinatumomab in adult ALL, and in this context we … included patients with latent relapses, and the clinical response rate was 69%.”

Patients received blinatumomab via continuous IV infusion in a 4-weeks-on, 2-weeks-off regimen.

Patients received a median of two cycles (range, 1-5). The first cycle including 9 microgram daily doses, and patients who responded went on to receive 28 micrograms daily.

Overall, 43% of patients achieved complete remission or complete remission with partial hematological recovery. Responses occurred across patient subgroups — including patients who had and had not undergone prior allogeneic stem cell transplantation or salvage therapy — and 80% of responses occurred during the first cycle.

Of the responders, 74% demonstrated minimal residual disease response.

Median RFS was 5.9 months (95% CI, 5.0-8.4), and median OS was 6.1 months (95% CI, 4.2-7.5).

The most frequently observed adverse events of all grades were pyrexia (59%), headache (35%) and febrile neutropenia (29%).

The most common grade ≥3 adverse events were febrile neutropenia (26%), anemia (15%) and neutropenia (15%), and 2% of patients had grade ≥3 cytokine release syndrome. Headache (4%), encephalopathy (3%) and ataxia (2%) were the most common grade ≥3 nervous system disorders.

Three patients experienced treatment-related grade 5 adverse events. They included two cases of sepsis and one case of candida infection.

A randomized phase 3 trial of blinatumomab in this patient population is underway, Topp said.

For more information:

Topp MS. Abstract #7005. Presented at: ASCO Annual Meeting; May 30-June 3, 2014; Chicago.

Disclosure: The researchers report consultant/advisory roles or employment/leadership positions with, honoraria or research funding from, and stock ownership in Amgen, Amgen Research Munich GmbH and GRAALL Intergroup.