FDA Approves Blinatumomab for Early-Stage CD19-Positive B-ALL
核心洞察
The FDA has approved blinatumomab for adult and pediatric patients with CD19 (搜索)-positive, Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (搜索) (B-ALL (搜索)) in the consolidation phase.
The approval was based on the Phase 3 E1910 trial, which showed a significant improvement in overall survival when blinatumomab was added to consolidation chemotherapy.
In the E1910 study, the 3-year OS rate was 84.8% in the blinatumomab arm compared to 69% in the chemotherapy arm (HR, 0.42; 95% CI, 0.24-0.75; P = 0.003).
The FDA has expanded the approval of blinatumomab (Blincyto) for the treatment of adult and pediatric patients one month and older with CD19 (搜索)-positive, Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (搜索) (Ph-negative BCP ALL) in the consolidation phase of multiphase chemotherapy. This decision marks a significant advancement in the treatment of B-ALL (搜索), offering a new standard of care to reduce relapse risk and improve survival rates.
The approval is primarily based on data from the Phase 3 E1910 trial (NCT02003222), sponsored by the National Cancer Institute and ECOG-ACRIN Cancer Research Group (搜索). The study demonstrated a significant improvement in overall survival (OS) when blinatumomab was added to consolidation chemotherapy in patients with B-ALL (搜索).
E1910 Trial Results
The E1910 trial was a randomized, controlled study in adult patients with newly diagnosed Ph-negative BCP ALL. 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 multiple blinatumomab monotherapy cycles plus intensive chemotherapy or intensive chemotherapy alone.
After a median follow-up of 43 months, the median OS was not reached in the chemotherapy plus blinatumomab arm compared with 6 years in the control arm (HR, 0.42; 95% CI, 0.24-0.75; P =.003). 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. 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).
Study 20120215
Efficacy was also 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. 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).
Adverse Reactions
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.
Clinical Significance
According to Mark R. Litzow, MD, lead study author and a professor of medicine (now retired) at the Mayo Clinic in Rochester, Minnesota, adding blinatumomab to the chemotherapy regimen lessened the risk of relapse and improved survival. He believes this is a new standard of care.
This approval marks the third indication for blinatumomab in ALL. Blinatumomab has been previously approved for patients with Philadelphia chromosome-negative relapsed or refractory B-ALL (搜索) and B-ALL in first or second complete remission with positive minimal residual disease (MRD).