Blincyto Plus Consolidation Chemotherapy Produces Significant Survival Improvement in MRD-Negative Acute Lymphoblastic Leukemia

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Blincyto (blinatumomab; Amgen) added to consolidation chemotherapy produced a significant improvement in overall survival (OS) among adults with measurable residual disease (MRD)-negative remission from B-cell precursor acute lymphoblastic leukemia (BCP-ALL), according to findings from a randomized Phase III trial (NCT02003222) published by The New England Journal of Medicine.^1,2

“Various developments in the past decade have led to improved outcomes in adults with B-cell precursor acute lymphoblastic leukemia (BCP-ALL),” the study authors wrote. “These include the use of pediatric-like intensive chemotherapy regimens in adolescents and young adults, the assessment of measurable residual disease (MRD) for prognostication and management decisions, and the development of immunotherapies. Despite these advances, outcomes in adults with BCP-ALL are inferior to those in children, owing in part to the increased frequency of high-risk genetic abnormalities and to the toxic effects of high-dose chemotherapy.”¹

Blincyto, a bispecific T-cell engager molecule, was approved by the FDA on June 14, 2024, to treat CD19-positive Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (B-ALL) in the consolidation phase in patients aged one month and above.³ It also has approved indications for adult and pediatric patients aged one month or older with CD19-positive B-ALL in first or second complete remission with MRD greater than or equal to 0.1% and for adult and pediatric patients aged one month or older with relapsed or refractory CD19-positive B-ALL.

“A phase 3 randomized trial of [Blincyto] as compared with chemotherapy for the treatment of relapsed or refractory BCR::ABL1-negative BCP-ALL (with :: indicating fusion) showed improved outcomes and led to the approval of [Blincyto] by the (FDA) for this indication in 2014,” the study authors wrote. “A subsequent study involving patients with MRD-positive BCP-ALL showed that after one 4-week cycle of blinatumomab, 78% of the patients had MRD-negative status. This finding led the FDA to expand the approval of blinatumomab to include MRD-positive BCP-ALL in 2018.”¹

For the current trial, investigators randomly assigned 488 patients aged 30 to 70 years (median age 51 years) with BCR::ABL1-negative BCP-ALL who had MRD-negative remission following induction and intensification chemotherapy. Patients were administered four cycles of Blincyto as well as four cycles of consolidation chemotherapy or four cycles of consolidation chemotherapy alone. The trial’s primary endpoint was OS, with a key secondary endpoint of relapse-free survival (RFS).

The results show that 81% of patients enrolled in the trial had complete remission with or without full count recovery. Among 224 patients with MRD-negative status, 112 were randomly assigned to each group, with balanced patient characteristics between groups.

At a median follow-up of 43 months, investigators observed 85% OS in the Blincyto cohort compared to 68% in the chemotherapy-only cohort (hazard ratio for death, 0.41; 95% confidence interval [CI], 0.23 to 0.73; P=0.002). Three-year RFS was 80% in the Blincyto cohort compared to 64% in the chemotherapy alone cohort (hazard ratio for relapse or death, 0.53; 95% CI, 0.32 to 0.87). Investigators observed a greater incidence of neuropsychiatric events in the Blincyto cohort compared to the chemotherapy-only cohort.

“This randomized phase 3 trial showed an overall survival benefit with blinatumomab added to consolidation chemotherapy in patients with BCR::ABL1-negative disease who were 30 and 70 years of age and had BCP-ALL in MRD-negative remission,” the study authors wrote. “Because these patients have a better prognosis than those with MRD-positive remission, an intentional prolonged follow-up was necessary to have enough events to show a benefit with regard to overall survival. Although the trial was not powered for subgroup analyses, patients younger than 55 years of age appeared to have the greatest benefit.”¹

References

1. Litzow M, et al. Blinatumomab for MRD-Negative Acute Lymphoblastic Leukemia in Adults. N Engl J Med 2024;391:320-333. DOI: 10.1056/NEJMoa2312948. Vol. 391 No. 4.

2. Combination Chemotherapy With or Without Blinatumomab in Treating Patients With Newly Diagnosed BCR-ABL-Negative B Lineage Acute Lymphoblastic Leukemia. ClinicalTrials.gov. December 15, 2023.

3. FDA Approves Blincyto® (Blinatumomab) In CD19-Positive Philadelphia Chromosome-Negative B-Cell Precursor Acute Lymphoblastic Leukemia (B-ALL) in the Consolidation Phase. Amgen. June 14, 2024. Accessed July 25, 2024. https://www.amgen.com/newsroom/press-releases/2024/06/fda-approves-blincyto-blinatumomab-in-cd19positive-philadelphia-chromosomenegative-bcell-precursor-acute-lymphoblastic-leukemia-ball-in-the-consolidation-phase