On June 14, 2024, the U.S. Food and Drug Administration (FDA) approved blinatumomab (Blincyto®) for adult and pediatric patients one month and older with CD19-positive, Philadelphia chromosome–negative, B-cell precursor acute lymphoblastic leukemia (Ph-negative BCP ALL) in the consolidation phase of multiphase chemotherapy.

FDA update

Efficacy was evaluated in Study E1910 (NCT02003222), a randomized, controlled trial in adult patients with newly diagnosed Ph-negative BCP ALL. Eligible patients in hematologic complete remission (CR) or CR with incomplete peripheral blood count recovery (CRi) following induction and intensification chemotherapy were randomized 1:1 to receive either:

  • A consolidation regimen comprised of multiple blinatumomab monotherapy cycles plus multiple cycles of intensive chemotherapy (blinatumomab arm; n = 112)
  • Intensive chemotherapy alone (chemotherapy arm; n = 112)

Randomization was stratified by age, CD20 status, rituximab use, and intent to undergo allogeneic hematopoietic stem cell transplantation (HSCT).

The major efficacy outcome measure was overall survival (OS). The 3-year OS was 84.8% (95% CI = 76.3, 90.4) and 69% (95% CI = 58.7, 77.2) in the blinatumomab and chemotherapy arms, respectively. The hazard ratio for OS was 0.42 (95% CI = 0.24, 0.75; p = 0.003). In a later analysis with a median follow-up of 4.5 years, the 5-year OS 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).

Efficacy also was evaluated in Study 20120215 (NCT02393859), a randomized, controlled, open-label, multicenter trial. Pediatric and young adult patients with Ph-negative BCP ALL were randomized 1:1 to receive blinatumomab (n = 54) or the IntReALLHR2010 HC3 intensive combination chemotherapy (n = 57) as the third consolidation cycle. Randomization was stratified by age, minimal 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.

The major efficacy outcome measures were OS and relapse-free survival (RFS). The 5‑year OS 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 (OS HR = 0.35 [95% CI = 0.17, 0.70]). The 5-year RFS 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 (RFS HR = 0.38 [95% CI = 0.22, 0.66].

In Study E1910, the most common adverse reactions reported in at least 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 reported in at least 20% of patients in the blinatumomab arm were pyrexia, nausea, headache, rash, hypogammaglobulinemia, and anemia.

See the full prescribing information for the recommended dose by patient weight and schedule.

FDA conducted the review under Project Orbis, an initiative of the FDA Oncology Center of Excellence (OCE). Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For the review, 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.

The applicant 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. FDA granted the application priority review, breakthrough designation, and orphan drug designation. FDA’s expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.

For assistance with single-patient applications for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.