he immunotherapy blinatumomab was found to improve overall survival for patients with no measurable residual disease (a status known as MRD negative) after initial treatment for B-lineage acute lymphoblastic leukaemia (ALL) according to a phase III trial being presented during the 64th American Society of Hematology (ASH) Annual Meeting and Exposition. The findings suggest that blinatumomab—which is currently 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 all patients with this cancer, according to researchers.
“Our study shows that adding blinatumomab to chemotherapy keeps patients in remission and improves their survival,” said 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 leukaemia 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 leukaemia after the initial course of chemotherapy (MRD positive), a group at a relatively high risk of relapse. The new trial demonstrates blinatumomab also brings significant benefits for patients without detectable disease after initial treatment (MRD negative), who generally have a better prognosis.
The trial enrolled 488 adults with newly diagnosed 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 leukaemia 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.
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. Seventeen of those receiving blinatumomab and 39 of those receiving chemotherapy alone died by the time of this 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 favourable risk group, and the study showed that it did,” said Dr. Litzow.
The trial initially randomized MRD-positive patients to the two study arms, but this randomization ended after the FDA approved the drug for this patient population in 2018. Moving forward, all patients who are MRD positive in the trial were assigned to the arm providing blinatumomab plus chemotherapy while patients who are MRD negative continued to be randomized.
The study found no new safety concerns associated with the use of blinatumomab, and used 72- and 96-hour infusions in 72% of the patients. These infusion times proved necessary to feasibly conduct the trial. The researchers plan to further analyse the data to determine whether particular subgroups of patients are more likely to benefit from blinatumomab than others.
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.
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