Blinatumomab Significantly Improves OS in Newly Diagnosed B-ALL Patients Who Are MRD Negative After Initial Treatment

Consolidation therapy with blinatumomab significantly improves overall survival (OS) in adult patients newly diagnosed with B-cell acute lymphoblastic leukemia (B-ALL) who had no measurable residual disease (MRD negative) following initial treatment, according to results presented today at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition, held in New Orleans, Louisiana.

Findings from the phase 3 ECOG-ACRIN E1910 trial, presented in a late-breaking session by Mark Litzow, MD, professor of medicine, Division of Hematology at Mayo Clinic in Rochester, Minnesota, show that blinatumomab (Blincyto), has broader use in early treatment beyond its current approval. Today, indications are for treatment of patients with B-ALL who are MRD positive and in remission, or for patients who do not respond to chemotherapy or relapse after first-line treatment.

Data for this interim analysis show that patients receiving blinatumomab with consolidation chemotherapy had an OS of 83% compared with 65% among those receiving consolidation chemotherapy alone. In a press briefing, Litzow showed that the survival curve for the blinatumomab arm has plateaued, while the curve for the control arm continues to fall.

Blinatumomab is among the bispecific antibodies that have been the stars at this year’s ASH meeting, stealing the limelight that chimeric antigen receptor (CAR) T-cell therapies have held in recent years. As Litzow explained, blinatumomab is a bispecific T-cell engager (BiTE) molecule, which works by bring a normal T-cell in proximity with a leukemia blast cell, killing it.

Why give blinatumomab to patients who are MRD negative? “We know that even though we can’t find leukemia in these patients’ bone marrow, it’s still hiding there,” Litzow said during the briefing.

The trial enrolled 488 adults at 77 sites in the United States, Canada, and Israel. Patients received a course of standard combination induction chemotherapy for 2.5 months. Those who were in remission after this treatment moved on to an intensification phase, which aimed to keep the leukemia from reaching the central nervous system—where relapse often occurs. MRD status was tested at a central laboratory, and patients were randomly assigned participants to receive either a standard course of consolidation chemotherapy or chemotherapy with 4 cycles of blinatumomab.

Both arms received maintenance therapy and were monitored for 2.5 years, and during this time treating physicians had the option to refer patients for stem cell transplant.

Results. In a planned interim analysis at 43 months, the median OS for the chemotherapy alone arm was 71.4 months, while the median OS for the blinatumomab with chemotherapy arm was not reached (HR 0.42; 95% CI, 0.24 to 0.75; P = .003).

Across both arms, 17 patients in the blinatumomab arm and 39 receiving chemotherapy alone had died at the time of the interim analysis.

During the briefing, both Litzow and ASH Secretary Cynthia Dunbar, MD, chief of the Translational Stem Cell Biology Branch within the Intramural Research Program of the National Heart, Lung, and Blood Institute at the National Institutes of Health, said the findings were practice changing.

“Patients who are MRD negative have a better prognosis than patients who are MRD positive, generally, but they still relapse,” Litzow said. “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.”

The randomized trial was conducted by the National Cancer Institute Clinical Trials Network.

Reference

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 3 National Cooperative Clinical Trials Network Trial. Presented at: 64th American Society of Hematology Annual Meeting and Exposition; New Orleans, Louisiana, December 10-13, 2022; Abstract LBA-1.