Adding blinatumomab to consolidation chemotherapy improved survival in patients with newly diagnosed B-lineage acute lymphoblastic leukemia (ALL) who were minimal residual disease (MRD) negative, according to results from a phase III trial.
Mark R. Litzow, MD, of the Mayo Clinic, and colleagues conducted the trial and presented its results during the 2022 American Society of Hematology Annual Meeting and Exposition.
Blinatumomab, a bispecific T-cell engager, is approved by the U.S. Food and Drug Administration (FDA) for patients with B-lineage ALL who have relapsed/refractory disease or who have a morphological complete response but are MRD positive.
Dr. Litzow and colleagues randomized patients to receive consolidation chemotherapy with or without blinatumomab to evaluate if adding blinatumomab improves outcomes in patients who become MRD negative after induction chemotherapy.
The study enrolled 488 patients aged 30 to 70 years old who had newly diagnosed BCR–ABL1-negative B-lineage ALL. The median patient age was 51 years. Patients initially received 2.5 months of combination induction chemotherapy with extended remission induction, plus pegaspargase for patients 55 years or older, and with the addition of rituximab for patients who were CD20-positive.
After remission induction, patients who were in morphologic complete remission continued in the study and received an intensification course of high-dose methotrexate with pegaspargase as central nervous system prophylaxis. The researchers determined the patients’ remission and MRD status centrally by flow cytometry, defining MRD negativity as <0.01%.
The study’s investigators randomized patients to receive an additional four cycles of consolidation chemotherapy, or two cycles of blinatumomab, followed by three cycles of consolidation chemotherapy, a third cycle of blinatumomab, a fourth cycle of consolidation chemotherapy, and a fourth cycle of blinatumomab. Patients in both treatment arms received four cycles of consolidation chemotherapy at the same doses.
After consolidation chemotherapy with or without blinatumomab, patients received 2.5 years of maintenance therapy with 6-mercaptopurine, vincristine, methotrexate, and prednisone.
“Patients proceeded to allogeneic hematopoietic [stem] cell transplant at the discretion of the treating physician, which was suggested to be done after the first two cycles of [blinatumomab] in the [blinatumomab] arm or at any time following intensification chemo in the control chemo arm,” Dr. Litzow and colleagues wrote. “Following the FDA approval of [blinatumomab] for MRD-positive disease in March 2018 [patients] who were MRD positive after intensification were assigned to the [blinatumomab] arm of the trial and no longer randomized.”
The trial’s primary objective was to compare the overall survival (OS) in MRD-negative patients who received blinatumomab plus chemotherapy with the OS of patients who received chemotherapy alone.
Patients who received blinatumomab plus chemotherapy had significantly improved median OS (not reached) compared with those who received chemotherapy alone (71.4 months; hazard ratio [HR], 0.42; 95% CI, 0.24-0.75; two-sided P=.003).
The complete remission rate was 81% after induction chemotherapy. Overall, 25% of the 224 patients who were MRD negative died, including 15.2% of the 112 patients receiving blinatumomab plus chemotherapy and 34.8% of the 112 patients receiving chemotherapy.
“The addition of [blinatumomab] to consolidation chemo resulted in a significantly better overall survival in [patients] with newly diagnosed B-lineage ALL who were MRD negative after intensification chemo,” Dr. Litzow and colleagues concluded. “No significant safety concerns were noted. The addition of [blinatumomab] to consolidation [chemotherapy] in adult [patients] aged 30-70 years represents a new standard of care for BCR–ABL1-negative ALL.”
Litzow MR, Sun Z, Paietta E, et al. Consolidation therapy with blinatumomab improves overall survival in newly diagnosed adult patients with B-lineage acute lymphoblastic leukemia in measurable residual disease negative remission: results from the ECOG-ACRIN E1910 randomized phase III National Cooperative Clinical Trials Network trial. Abstract LBA-1. Presented at the 64th ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, Louisiana.