The Food and Drug Administration (FDA) has granted approval for blinatumomab (Blincyto, Amgen) for use in adult and pediatric patients aged one month and older with CD19-positive Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (Ph-negative BCP ALL) during the consolidation phase of multiphase chemotherapy. This decision marks a significant advancement in the treatment regimen for this specific leukemia subset.
Image Source: Vinoth Khandelwal
Blinatumomab’s approval follows extensive regulatory review, involving collaboration with international regulatory bodies under the FDA’s Project Orbis initiative. This initiative allows for concurrent submission and review of oncology drugs among international partners, including agencies from Brazil, Canada, Switzerland, and the United Kingdom. The review process was expedited using the Real-Time Oncology Review (RTOR) pilot program and the Assessment Aid, facilitating a streamlined evaluation and approval process. Blinatumomab was granted priority review, breakthrough therapy designation, and orphan drug designation.
Blinatumomab is a bispecific T-cell engager (BiTE) immunotherapy that binds to CD19 on B-cell lymphoblasts and CD3 on T-cells, facilitating T-cell-mediated destruction of the malignant cells. This mechanism of action is particularly effective in targeting and eliminating B-cell precursor leukemic cells.
The efficacy of blinatumomab was primarily evaluated through two significant studies:
Study E1910 (NCT02003222)
This randomized, controlled trial included adult patients with newly diagnosed Ph-negative BCP ALL. Patients in hematologic complete remission (CR) or CR with incomplete peripheral blood count recovery (CRi) post-induction and intensification chemotherapy were randomized to receive either a consolidation regimen of blinatumomab monotherapy plus intensive chemotherapy (blinatumomab arm) or intensive chemotherapy alone (chemotherapy arm). The study included 112 patients in each arm. The primary efficacy outcome was overall survival (OS). The 3-year OS was significantly higher in the blinatumomab arm (84.8%) compared to the chemotherapy arm (69%), with a hazard ratio (HR) for OS of 0.42. A follow-up analysis with a median duration of 4.5 years demonstrated a 5-year OS of 82.4% in the blinatumomab arm versus 62.5% in the chemotherapy arm, with a hazard ratio of 0.44.
Study 20120215 (NCT02393859)
This randomized, controlled, open-label, multicenter trial included pediatric and young adult patients. Participants were randomized to receive either blinatumomab or the IntReALL HR2010 HC3 intensive combination chemotherapy as the third consolidation cycle. This study involved 54 patients in the blinatumomab arm and 57 in the chemotherapy arm. The major efficacy outcomes were overall survival (OS) and relapse-free survival (RFS). The 5-year OS was 78.4% for the blinatumomab arm compared to 41.4% for the chemotherapy arm. Similarly, the 5-year RFS was 61.1% for the blinatumomab arm versus 27.6% for the chemotherapy arm.
Ph-negative BCP ALL is a form of acute lymphoblastic leukemia characterized by the absence of the Philadelphia chromosome and the presence of CD19 markers on B-cell precursors. It primarily affects children and young adults but can also occur in older adults. The prognosis and treatment outcomes for this leukemia subtype vary, and consolidation therapy is crucial for maintaining remission and improving long-term survival.
The approval of blinatumomab for the consolidation phase of treatment in patients with CD19-positive Ph-negative BCP ALL represents a significant advancement in leukemia therapy, offering improved survival outcomes and a new therapeutic option for both adult and pediatric patients. This milestone underscores the importance of innovative immunotherapies in enhancing cancer treatment efficacy and patient prognosis.
Dr. Vinoth Khandelwal, Ph.D.
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