The bispecific T-cell engager molecule blinatumomab was found to improve overall survival for patients with no measurable residual disease (MRD) after initial treatment for B-lineage acute lymphoblastic leukemia (ALL), according to the phase III ECOG-ACRIN E1910 trial presented by Litzow et al at the 2022 American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract LBA-1). The findings suggest that blinatumomab—which is currently U.S. Food and Drug Administration (FDA)-approved for patients with MRD-positive B-lineage ALL who are in remission and those who do not respond to chemotherapy or relapse after an initial response—is safe and effective as a first-line therapy for patients with this cancer, according to researchers.

“Our study shows that adding blinatumomab to chemotherapy keeps patients in remission and improves their survival,” said presenting author Mark Litzow, MD, of Mayo Clinic in Rochester, Minnesota. “Based on what we’re finding, I think this is the new standard of care.”

Blinatumomab is a bispecific antibody that works by bringing a patient’s T cells into close proximity to leukemia cells so that the immune system can destroy the cancer. Previous studies have found that it improves outcomes for patients with a detectable amount of leukemia after the initial course of chemotherapy (MRD-positive), a group at a relatively high risk of relapse. The ECOG-ACRIN E1910 trial demonstrated blinatumomab also brings significant benefits for patients without detectable disease after initial treatment (MRD-negative), who generally have a better prognosis.

ECOG-ACRIN E1910 Details

The trial enrolled 488 newly diagnosed adult patients with B-lineage ALL at 77 clinical sites in the United States, Canada, and Israel. All participants received an initial course of standard combination induction chemotherapy for 2.5 months. Patients who were in remission at the end of induction treatment moved on to an intensification phase. The purpose of intensification was to stop leukemia from developing in the central nervous system—a common site of relapse if not prevented.

Researchers determined MRD status (negative or positive) at a central testing laboratory after the intensification phase, then randomly assigned participants to receive either a standard course of consolidation chemotherapy or chemotherapy interspersed with four cycles of blinatumomab. Following this, participants were monitored for 2.5 years while taking standard maintenance therapy. The trial included the option for patients to proceed to a stem cell transplant at the discretion of the treating physician.

Outcomes

In a planned interim analysis at a median of 43 months, researchers assessed outcomes among 224 patients who were MRD-negative following induction chemotherapy. The results showed patients who received blinatumomab plus chemotherapy during the consolidation phase fared significantly better, with an overall survival rate of 83% compared with 65% among patients receiving consolidation chemotherapy alone. A total of 17 of those receiving blinatumomab and 39 of those receiving chemotherapy alone died by the time of the interim analysis.

“Patients who are MRD-negative have a better prognosis than patients who are MRD-positive, generally, but they still relapse. We think we can do better, so we wanted to see if blinatumomab would improve the results in this already somewhat favorable risk group, and the study showed that it did,” said Dr. Litzow.

Initially, the trial randomly assigned MRD-positive patients to the two study arms, but this random assignment ended after the FDA approved the drug for this patient population in 2018. Moving forward, all patients who were MRD-positive in the trial were assigned to the arm providing blinatumomab plus chemotherapy, while patients who were MRD-negative continued to be randomly assigned.

The study found no new safety concerns associated with the use of blinatumomab. Researchers used 72- and 96-hour infusions in 72% of the patients; these infusion times proved necessary to feasibly conduct the trial.

The team plans to further analyze the data to determine whether particular subgroups of patients are more likely to benefit from blinatumomab than others.

Disclosure: The trial was designed and conducted by the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) with participation from the National Clinical Trials Network funded by the National Cancer Institute, part of the National Institutes of Health. Amgen, the manufacturer of blinatumomab, provided support and the drug used in the study under a Cooperative Research and Development Agreement with NCI. For full disclosures of the study authors, visit ash.confex.com.