Amgen's BiTE Immunotherapy Blincyto Demonstrates Significant Efficacy in Phase 3 Trial for Pediatric Acute Lymphoblastic Leukemia

March 08, 2021 News /BioValleyBIOON/ -- Amgen recently announced the evaluation of the BiTE immunotherapy Blincyto (blinatumomab) for the treatment of acute lymphoblastic leukemiaLeukemiaData from a multicenter, randomized, phase 3 clinical study (20120215, NCT02393859) of Blincyto in pediatric patients with acute lymphoblastic leukemia (ALL) have been published in JAMA. In addition, results from a risk-stratified, randomized, phase 3 clinical study (COG AALL1331) evaluating Blincyto for the treatment of pediatric patients with B-cell precursor ALL in first relapse were also published in JAMA. In both studies, Blincyto demonstrated a more favorable toxicity profile and higher rates of minimal residual disease (MRD)-negative remission.

Blincyto is the first and only CD19-CD3 bispecific T-cell engager (BiTE) immunotherapy approved globally, and it is also the first bispecific antibody product developed from Amgen’s BiTE technology platform. It works by presenting the CD19 protein on tumor cells to the CD3 protein specifically expressed on T cells, thereby activating the immune system to recognize and killTumorCells.

David M. Reese, Executive Vice President of Research and Development at Amgen, stated, “Acute lymphoblastic leukemia (ALL) is the most common type of cancer in children. Unfortunately, approximately 15% of pediatric patients with high-risk B-ALL experience relapse after first-line chemotherapy, and there remains an urgent unmet need for new treatment options for these patients. The aforementioned study results support Blincyto as a new standard of care for consolidation therapy in patients with this aggressive disease.”

Study 20120215 was an open-label, randomized, controlled, global, multicenter Phase 3 study conducted in pediatric patients with high-risk, first-relapse B-cell precursor acute lymphoblastic leukemia (B-ALL), comparing allogeneic hematopoieticStem CellsEfficacy, Safety, and Tolerability of Blincyto or Consolidation Chemotherapy Prior to Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT). In September 2019, patient enrollment in the study was terminated early upon the recommendation of the Independent Data Monitoring Committee (DMC) due to the encouraging efficacy observed in the Blincyto treatment group. Subsequent activities will continue to proceed in accordance with the clinical protocol.

Results published in JAMA showed that, compared with chemotherapy, Blincyto significantly prolonged event-free survival (events defined as relapse, death, second malignantTumor, failure to achieve complete remission). After a median follow-up of 22.4 months, 69% of patients in the Blincyto treatment group were alive and event-free, compared with 43% in the chemotherapy group. Furthermore, among patients with minimal residual disease (MRD) at baseline, 93% of those treated with Blincyto achieved MRD-negative remission, versus 24% in the chemotherapy group. The estimated 36-month overall survival (OS) rate was 81.1% for the Blincyto group and 55.8% for the chemotherapy group; median OS had not been reached.

In this study, the incidence rates of serious adverse events (AEs) in the Blincyto group and the chemotherapy group were 24.1% and 43.1%, respectively, and the incidence rates of grade ≥3 adverse events were 57.4% and 82.4%, respectively. No fatal adverse events were reported. The most commonAdverse Reactions(AE) were fever (81.5%), nausea (40.7%), headache (35.2%), stomatitis (35.2%), and vomiting (29.6%).

Investigators of the study, Department of Pediatric Hematology at Bambino Gesù Children's Hospital, University of Rome, andTumorFranco Locatelli, a departmental researcher, stated: “The study results show that Blincyto is more effective and less toxic than intensive chemotherapy, which I find very exciting. In patients receivingStem Cells“Prior to transplantation, chemotherapy has been used as the primary consolidation therapy for all patients, although this approach is only partially effective and is associated with related toxicities. Blincyto has currently been demonstrated to be a more effective and safer consolidation therapy regimen for children with high-risk first relapse of B-ALL.”

Mechanism of Action of BiTE Immunotherapy

BiTE antibody technology represents an innovative immunotherapy approach that is effective at very low concentrations. Amgen acquired the BiTE technology after purchasing Micromet for $1.2 billion in 2012. Currently, Amgen is extensively addressing refractoryTumorExploring the Potential of BiTE Innovative Therapies by Type.

Blincyto is the first bispecific antibody product developed from Amgen’s BiTE technology platform. Previously, the United StatesFDABlincyto has been granted Orphan Drug Designation (ODD), Breakthrough Therapy Designation (BTD), and Priority Review for the treatment of various types of hematologic cancers, including acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), hairy cell leukemia (HCL), prolymphocytic leukemia (PLL), indolent B-cell lymphomas, and mantle cell leukemia (MCL).

In the United States, Blincyto has been approved for the treatment of: (1) adult and pediatric patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL); (2) adult and pediatric patients with B-cell precursor ALL who have minimal residual disease (MRD) ≥0.1% at first or second complete remission.

In the European Union, Blincyto has been approved for the treatment of: (1) adult patients with Philadelphia chromosome-negative, CD19-positive, relapsed or refractory acute lymphoblastic leukemia (ALL); (2) adult patients with Philadelphia chromosome-negative, CD19-positive B-cell precursor ALL who have minimal residual disease (MRD) ≥0.1% at first or second complete remission; (3)Stem CellsPediatric patients (≥1 year of age) with Philadelphia chromosome-negative, CD19-positive B-cell precursor acute lymphoblastic leukemia who have relapsed after transplantation.

In patients with acute lymphoblastic leukemia (ALL), detection of residual cancer cells (i.e., minimal residual disease, MRD) after complete remission is the strongest prognostic factor for assessing disease relapse. Notably, Blincyto is the first therapy approved by regulatory authorities in the United States and the European Union for the eradication of MRD. (Bioon.com)

Original Source: BLINCYTO® (Blinatumomab) Demonstrated Significantly Prolonged Event-Free Survival Compared With Consolidation Chemotherapy In Pediatric Patients With Relapsed Acute Lymphoblastic Leukemia