On 14 June 2024, the US Food and Drug Administration (FDA) approved blinatumomab (Blincyto, Amgen Inc.) for adult and paediatric patients one month and older with CD19-positive Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukaemia (Ph-negative BCP ALL) in the consolidation phase of multiphase chemotherapy.
Efficacy was evaluated in Study E1910 (NCT02003222), a randomised, controlled study in adult patients with newly diagnosed Ph-negative BCP ALL. Eligible patients in haematologic complete remission (CR) or CR with incomplete peripheral blood count recovery (CRi) following induction and intensification chemotherapy were randomised 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). Randomisation was stratified by age, CD20 status, rituximab use, and intent to undergo allogeneic haematopoietic stem cell transplantation. There were 112 patients randomised to the blinatumomab arm and 112 to the chemotherapy arm.
The major efficacy outcome measure was overall survival (OS). The 3-year OS 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 OS was 0.42 (95% CI 0.24, 0.75; p-value = 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 HR was 0.44 (95% CI 0.25, 0.76).
Efficacy also was evaluated in Study 20120215 (NCT02393859), a randomised, controlled, open-label, multicentre study. Paediatric and young adult patients with Ph-negative BCP ALL were randomised 1:1 to receive blinatumomab or the IntReALLHR2010 HC3 intensive combination chemotherapy as the third consolidation cycle. Randomisation 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. There were 54 patients randomised to the blinatumomab arm and 57 to the chemotherapy arm.
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 (HR for OS 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 (HR for RFS 0.38, 95% CI 0.22, 0.66).
In Study E1910, the most common adverse reactions (≥20%) in the blinatumomab arm were neutropenia, thrombocytopenia, anaemia, leukopenia, headache, infection, nausea, lymphopenia, diarrhoea, musculoskeletal pain, and tremor.
In Study 20120215, the most common adverse reactions (≥20%) in the blinatumomab arm were pyrexia, nausea, headache, rash, hypogammaglobulinemia, and anaemia.
This review was conducted under Project Orbis, an initiative of the FDA’s Oncology Center of Excellence (OCE). Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Brazilian Health Regulatory Agency, Health Canada, 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 programme, 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 designation, and orphan drug designation.
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.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate.