ASH 2014: Blinatumomab Achieves Complete Molecular Responses in Majority of B-Cell Leukemia Patients
Results from the international phase II BLAST study show that one cycle of blinatumomab (Blincyto) immunotherapy achieved complete minimal residual disease response in 78% of patients with precursor B-cell acute lymphoblastic leukemia (ALL). Complete minimal residual disease response was achieved in 80% of patients across all cycles of blinatumomab. The findings were presented at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 379).
Minimal Residual Disease
The study is unique in that it used minimal residual disease status as part of inclusion criteria and minimal residual disease response as its primary endpoint. Minimal residual disease response is a measure of complete eradication of disease.
Patients can achieve a complete hematologic remission by conventional measures (ie, less than 5% blasts) and still have minimal residual disease at the molecular level, explained lead author Nicola Gökbuget, MD, of Goethe University Hospital, Frankfurt, Germany.
“It is now possible to assess minimal residual disease by quantitative measurement of individual T-cell receptor and immunoglobulin rearrangements in more than 90% of ALL patients. Minimal residual disease is a strong prognostic factor for relapse and overall survival. Nearly all patients with persistent or recurrent minimal residual disease relapse despite continued chemotherapy, and minimal residual disease persistence indicates resistance to conventional chemotherapy,” she told listeners at a press conference during the ASH Annual Meeting. “New approaches are needed to improve outcomes in patients with persistent or recurrent minimal residual disease.”
Blinatumomab has recently been granted U.S. Food and Drug Administration approval for treatment of patients with Philadelphia chromosome–negative precursor B-cell ALL. It is the first in a novel class of drugs called bispecific T-cell engagers (BiTE) and is designed to direct cytotoxic T cells to CD19-expressing cancer cells, found on the cell surface of B-cell ALL and non-Hodgkin lymphoma.
BLAST Trial
BLAST enrolled 116 adults with precursor B-cell ALL in complete hematologic remission (< 5% blasts after three cycles of chemotherapy) with minimal residual disease (ie, level ≥ 10-3). No prior allogeneic hematopoietic stem cell transplant was allowed.
All patients received one cycle of blinotumomab and were assessed for minimal residual disease. Patients continued on blinotumomab for up to three additional cycles and transplant-eligible patients with a donor received hematopoietic stem cell transplantation. They were followed for efficacy for 2 years.
Blinatumomab achieved minimal residual disease responses in patients regardless of age, minimal residual disease level at baseline, or relapse history. No predictive factor for response was identified.
Adverse events occurring in 20% or more of patents included immune reactions of pyrexia, fever, and chills; only 7% had grade 3 or higher fever. Gastrointestinal side effects occurred in about 22% of patients.
Twenty-nine percent of patients had tremor, and 13% had aphasia.
“Neurologic symptoms are clinically relevant, although most neurologic events on study were grades 1 or 2,” Dr. Gökbuget said.
The study was funded by Amgen. Dr. Gökbuget reported consultancy, honoraria, and research funding from Amgen. For full disclosures of the study authors, view the study abstract.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
