FDA Approves Blinatumomab as Consolidation for CD19-positive Philadelphia Chromosome-negative B-Cell

On June 14, 2024, the US Food and Drug Administration (FDA) granted approval for blinatumomab (Blincyto, Amgen Inc.) to be used in the consolidation phase of multiphase chemotherapy for 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).

The efficacy of treatment was assessed in Study E1910 (NCT02003222), which was a randomized, controlled study involving adult patients with newly diagnosed Ph-negative BCP ALL. Patients who achieved haematologic complete remission (CR) or CR with incomplete peripheral blood count recovery (CRi) following induction and intensification chemotherapy were randomly assigned in a 1:1 ratio to either receive a consolidation regimen consisting of multiple cycles of blinatumomab monotherapy combined with multiple cycles of intensive chemotherapy (blinatumomab arm) or to undergo intensive chemotherapy alone (chemotherapy arm). The randomization process was stratified based on age, CD20 status, rituximab use, and intention to undergo allogeneic hematopoietic stem cell transplantation. A total of 112 patients were assigned to the blinatumomab arm, while 112 were assigned to the chemotherapy arm.

The primary outcome measure of effectiveness was overall survival (OS). The 3-year OS rates were 84.8% (95% CI 76.3, 90.4) for patients receiving blinatumomab and 69% (95% CI 58.7, 77.2) for those receiving chemotherapy. The hazard ratio (HR) for OS was 0.42 (95% CI 0.24, 0.75; p-value = 0.003). In a subsequent analysis with a median follow-up of 4.5 years, the 5-year OS rates were 82.4% (95% CI 73.7, 88.4) for the blinatumomab group and 62.5% (95% CI 52.0, 71.3) for the chemotherapy group. The HR was 0.44 (95% CI 0.25, 0.76).

The effectiveness of the treatment was also assessed in Study 20120215 (NCT02393859), which was a randomized, controlled, open-label, multicenter study. Pediatric and young adult patients with Philadelphia chromosome-negative B cell precursor acute lymphoblastic leukemia (Ph-negative BCP ALL) were randomly assigned in a 1:1 ratio to receive either blinatumomab or the IntReALLHR2010 HC3 intensive combination chemotherapy as the third consolidation cycle. The randomization process was divided based on age, minimal residual disease status at the end of the initial treatment phase according to local assessment and bone marrow status at the conclusion of the second round of consolidation chemotherapy. In total, there were 54 patients randomized to the blinatumomab group and 57 patients to the chemotherapy group.

The main effectiveness measures analyzed were overall survival (OS) and relapse-free survival (RFS). After 5 years, the OS rates were 78.4% (95% CI 64.2, 87.4) in the blinatumomab group and 41.4% (95% CI 26.3, 55.9) in the chemotherapy group (HR for OS 0.35, 95% CI 0.17, 0.70). The 5-year RFS rates were 61.1% (95% CI 46.3, 72.9) with blinatumomab and 27.6% (95% CI 16.2, 40.3) with chemotherapy (HR for RFS 0.38, 95% CI 0.22, 0.66). 

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In Study E1910, the blinatumomab group experienced the following most frequent adverse reactions (≥20%): neutropenia, thrombocytopenia, anemia, leukopenia, headache, infection, nausea, lymphopenia, diarrhea, musculoskeletal pain, and tremor.

In the study 20120215, the most frequent adverse reactions (≥20%) in the group receiving blinatumomab were fever, nausea, headache, rash, low levels of gamma globulin, and anemia.