Blinatumomab plus consolidation chemotherapy demonstrated a survival advantage for patients with newly diagnosed minimal residual disease–negative B-cell acute lymphoblastic leukemia.
Patients with newly diagnosed minimal residual disease (MRD)-negative B-cell acute lymphoblastic leukemia (ALL) experienced a 58% reduction in the risk of death when treated with blinatumomab (Blincyto) compared with standard consolidation chemotherapy alone, according to phase 3 findings of the phase 3 ECOG-ACRIN E1910 trial.
Results, which were presented during the 2022 ASH Annual Meeting, showed that the median overall survival (OS) with blinatumomab plus chemotherapy was not reached (NR) compared with 71.4 months with chemotherapy alone (HR, 0.42; 95% CI, 0.24-0.75; P = .003). OS rates at a median follow-up of 3.6 years were 83% and 65%, respectively.
“This trial, E1910, showed for the first time, an OS advantage for adult patients with MRD-negative BCR-ABL–negative B-lineage acute lymphoblastic leukemia who receive blinatumomab combined with chemotherapy,” lead study author Mark R. Litzow, MD, a professor of medicine in the Division of Hematology at Mayo Clinic, said in a press briefing during the meeting. “We feel that this represented a new standard of care for this group of patients and should be incorporated into their standard therapy.”
Blinatumomab is a bispecific T-cell engager antibody that is designed to direct cytotoxic T cells to CD19-expressing cancer cells. The agent is currently approved for use in adult and pediatric patients with B-cell precursor ALL who are in remission but still have MRD, as well as in adult and pediatric patients with relapsed/refractory B-cell precursor ALL.
In the phase 3 ECOG-ACRIN E1910 trial, 488 patients in the United States, Canada, and Israel underwent standard induction chemotherapy for about 2 months to induce a remission, followed by intensification chemotherapy for approximately 1 month to treat leukemia in the central nervous system. A total 224 patients were then randomized 1:1 to receive intravenous blinatumomab for 2 monthly cycles, followed by 4 monthly cycles of consolidation chemotherapy and then 2 monthly cycles of blinatumomab (n = 112), or 4 monthly cycles of standard consolidation chemotherapy (n = 112). Maintenance chemotherapy was given in both arms for approximately 2.5 years.
The trial initially consisted of a cohort of MRD-positive patients doing a similar randomization. However, Litzow noted that following the FDA approval of blinatumomab in March 2018 for MRD-positive patients, these patients were no longer randomized on study but were assigned to the blinatumomab arm.
The standard induction chemotherapy regimen consisted of a BFM-type induction regimen that was modified from the E2993/UKALLXII trial, and then intensification therapy comprised high-dose methotrexate and pegaspargase.
Patients, who were aged between 30 and 70 years and had newly diagnosed, BCR-ABL1–negative, B-lineage ALL, were also tested for MRD via 6-color flow cytometry at the time of randomization, Litzow added. MRD negativity was defined as less than or equal to 0.01%.
Stratification factors included age, CD20 status, rituximab (Rituxan) use, and hematopoietic stem cell transplantation (yes vs no).
The primary end point was OS, which was measured from the time of randomization to blinatumomab or chemotherapy. Twenty-two patients in each arm proceeded to allogeneic hematopoietic stem cell transplant. The median age was 51 years (range, 30-70). The complete response (CR)/CR with incomplete count recovery (CRi) to induction chemotherapy was 81%; the CR rate was 75% and the CRi rate was 6%. Eighty percent of patients received 2 or more cycles of blinatumomab.
In September 2022, the ECOG-ACRIN Data Safety Monitoring Committee recommended that the study findings be released in favor of the efficacy in MRD-negative patients.
In the MRD-negative population, 17 deaths occurred on the blinatumomab arm (relapse, n = 8; non-relapse mortality [NRM], n = 9) vs 39 on the chemotherapy-alone arm (relapse, n = 20; NRM, n = 17; unknown, n = 2).
Further findings showed that the median relapse-free survival was NR compared with 22.4 months with chemotherapy (HR, 0.46; 95% CI, 0.27-0.78; P = .004).
In patients with MRD-positive disease, the median OS was also NR vs 22.4 months with chemotherapy alone (HR, 0.39; 95% CI, 0.14-1.10; P = .066). On this arm, 9 deaths occurred on the blinatumomab arm (ALL, n = 6; NRM = 1; unknown, n = 3), and 13 on the chemotherapy-alone arm (ALL, n = 7; NRM, n = 6).
Litzow MR, Sun Z, Paletta 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. Blood. 2022;140(suppl 2):LBA-1. doi:10.1182/blood-2022-171751