San Francisco, CA—In patients with acute lymphoblastic leukemia (ALL), assessment of minimal residual disease (MRD) is increasingly used to evaluate response to treatment. An antibody that recruits the body’s T-cells to attack MRD in patients with ALL whose disease is in remission can prevent full relapse.
In a recent phase 2 clinical trial of patients with ALL, no MRD was detected in 78% of the patients who received blinatumomab (Blincyto), a bispecific T-cell engager antibody construct; of these, nearly all complete responses occurred in the first cycle of treatment. The results of the trial were presented at the recent annual meeting of the American Society of Hematology.
Nearly all patients with ALL and persistent or recurrent MRD relapse despite continued chemotherapy, and patients with elevated MRD have a high relapse risk after stem-cell transplantation. Therefore, alternate treatment approaches to improve outcomes in patients with persistent or recurrent MRD are needed.
Blinatumomab directs cytotoxic T-cells to CD19-positive cells, resulting in serial lysis. “CD19 is a highly specific B-cell marker that is expressed throughout B-cell development and in more than 90% of B-cell lineage cancers,” said Nicola Gökbuget, MD, Hematologic Oncologist, Goethe University Hospital, Frankfurt, Germany. In a previous small pilot trial of 20 patients, blinatumomab produced an 80% MRD response.
In December, the FDA approved blinatumomab for the treatment of patients with Philadelphia chromosome–negative relapsed or refractory B-cell precursor ALL, “but the difference in this trial is that we treat the patients before the relapse,” Dr Gökbuget said.
In addition to evaluating blinatumomab in ALL, Dr Gökbuget’s study utilized a new, more sensitive method to detect MRD, using a polymerase chain reaction–based method of individual gene rearrangement to measure MRD.
The open-label confirmatory enrolled 116 patients with MRD-positive B-cell precursor ALL, defined as a level ?10–3 in an assay with a minimum sensitivity of 10–4, which is close to full relapse, said Dr Gökbuget.
Of the 116 patients, 112 were evaluable for complete MRD response, the primary end point. Blinatumomab was given by continuous intravenous infusion 15 µg/m2 daily for 28 days per cycle, followed by 2 weeks off, for up to a maximum of 4 cycles (each cycle followed by 2 weeks off). Hematopoietic stem-cell transplantation was offered to eligible patients at any time after the first cycle.
Of patients who received at least 1 dose of blinatumomab, 78% had a complete MRD response; 98% of the complete responses occurred within the first cycle. Among 103 patients who received at least 1 dose of blinatumomab and had an MRD ?10–3 at screening, 80% achieved a complete MRD response after cycle 1.
The 2 types of adverse events reported include events related to cytokine release (ie, fever, chills, fatigue) and neurologic events. “The most commonly occurring adverse events were flu-like symptoms associated with T-cell activation,” Dr Gökbuget said.
Pyrexia was the most common adverse event, which occurred in 90% of patients. Other events related to cytokine release were chills (28%) and fatigue (24%). The most common gastrointestinal adverse events were nausea (22%), vomiting (22%), and diarrhea (20%). Grade ?3 adverse events included neutropenia (16%), pyrexia (7%), and tremor (5%).
The most frequent neurologic adverse events were tremor (29%) and aphasia (13%). Dr Gökbuget noted that most adverse events were grade 1 or 2, but that they are clinically relevant, because they can lead to treatment interruption.
