On June 14, 2024, the U.S. Food and Drug Administration (FDA) approved blinatumomab (Blincyto) for adult and pediatric patients aged 1 month and older with CD19-positive, Philadelphia chromosome (Ph)-negative B-cell precursor acute lymphoblastic leukemia (ALL) in the consolidation phase of multiphase chemotherapy.
Study E1910
Efficacy was evaluated in Study E1910 (ClinicalTrials.gov identifier NCT02003222), a randomized, controlled trial in adult patients with newly diagnosed Ph-negative B-cell precursor ALL. Eligible patients in hematologic complete remission or complete remission with incomplete peripheral blood count recovery following induction and intensification chemotherapy were randomly assigned 1:1 to receive a consolidation regimen comprised of multiple blinatumomab monotherapy cycles plus multiple cycles of intensive chemotherapy (blinatumomab arm) or to intensive chemotherapy alone (chemotherapy arm). Random assignment was stratified by age, CD20 status, rituximab use, and intent to undergo allogeneic hematopoietic stem cell transplantation. There were 112 patients in the blinatumomab arm and 112 in the chemotherapy arm.
The major efficacy outcome measure was overall survival. The 3-year overall survival rate was 84.8% (95% confidence interval [CI] = 76.3%–90.4%) and 69% (95% CI = 58.7%–77.2%) in the blinatumomab and chemotherapy arms, respectively. The hazard ratio (HR) for overall survival was 0.42 (95% CI = 0.24–0.75, P = .003). In a later analysis with a median follow-up of 4.5 years, the 5-year overall survival was 82.4 % (95% CI = 73.7%–88.4%) in the blinatumomab arm and 62.5 % (95% CI = 52.0%–71.3%) in the chemotherapy arm. The hazard ratio was 0.44 (95% CI = 0.25–0.76).
Study 20120215
Efficacy also was evaluated in Study 20120215 (NCT02393859), a randomized, controlled, open-label, multicenter trial. Pediatric and young adult patients with Ph-negative B-cell precursor ALL were randomly assigned 1:1 to receive blinatumomab or the IntReALLHR2010 HC3 intensive combination chemotherapy as the third consolidation cycle. Random assignment was stratified by age, measurable residual disease status at the end of induction based on local assessment, and bone marrow status at the end of the second block of consolidation chemotherapy. There were 54 patients in the blinatumomab arm and 57 in the chemotherapy arm.
The major efficacy outcome measures were overall survival and relapse-free survival. The 5‑year overall survival rate was 78.4% (95% CI = 64.2%–87.4%) and 41.4% (95% CI = 26.3%–55.9%) in the blinatumomab and chemotherapy arms, respectively (HR = 0.35, 95% CI = 0.17–0.70). The 5-year relapse-free survival rate was 61.1% (95% CI = 46.3%–72.9%) and 27.6% (95% CI = 16.2%–40.3%) in the blinatumomab and chemotherapy arms, respectively (HR = 0.38, 95% CI = 0.22–0.66).
Adverse Events
In Study E1910, the most common adverse reactions (occurring in ≥ 20% of patients) in the blinatumomab arm were neutropenia, thrombocytopenia, anemia, leukopenia, headache, infection, nausea, lymphopenia, diarrhea, musculoskeletal pain, and tremor. In Study 20120215, the most common adverse reactions (occurring in ≥ 20% of patients) in the blinatumomab arm were pyrexia, nausea, headache, rash, hypogammaglobulinemia, and anemia.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for the concurrent submission and review of oncology drugs among international partners. For this review, the FDA collaborated with the Brazilian Health Regulatory Agency, Health Canada, Switzerland’s Swissmedic, and United Kingdom’s Medicines and Healthcare products Regulatory Agency. The application reviews are ongoing at the other regulatory agencies.
This review used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted Priority Review, Breakthrough Therapy designation, and Orphan Drug designation.
