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Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival
- Source :
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 29(18)
- Publication Year :
- 2011
-
Abstract
- Purpose Blinatumomab, a bispecific single-chain antibody targeting the CD19 antigen, is a member of a novel class of antibodies that redirect T cells for selective lysis of tumor cells. In acute lymphoblastic leukemia (ALL), persistence or relapse of minimal residual disease (MRD) after chemotherapy indicates resistance to chemotherapy and results in hematologic relapse. A phase II clinical study was conducted to determine the efficacy of blinatumomab in MRD-positive B-lineage ALL. Patients and Methods Patients with MRD persistence or relapse after induction and consolidation therapy were included. MRD was assessed by quantitative reverse transcriptase polymerase chain reaction for either rearrangements of immunoglobulin or T-cell receptor genes, or specific genetic aberrations. Blinatumomab was administered as a 4-week continuous intravenous infusion at a dose of 15 μg/m2/24 hours. Results Twenty-one patients were treated, of whom 16 patients became MRD negative. One patient was not evaluable due to a grade 3 adverse event leading to treatment discontinuation. Among the 16 responders, 12 patients had been molecularly refractory to previous chemotherapy. Probability for relapse-free survival is 78% at a median follow-up of 405 days. The most frequent grade 3 and 4 adverse event was lymphopenia, which was completely reversible like most other adverse events. Conclusion Blinatumomab is an efficacious and well-tolerated treatment in patients with MRD-positive B-lineage ALL after intensive chemotherapy. T cells engaged by blinatumomab seem capable of eradicating chemotherapy-resistant tumor cells that otherwise cause clinical relapse.
- Subjects :
- Male
Cancer Research
Neoplasm, Residual
CD3 Complex
medicine.medical_treatment
T-Cell Antigen Receptor Specificity
Kaplan-Meier Estimate
Lymphocyte Activation
Targeted therapy
Drug Delivery Systems
Agammaglobulinemia
Antibody Specificity
Bone Marrow
Antibodies, Bispecific
Molecular Targeted Therapy
Aged, 80 and over
B-Lymphocytes
biology
Remission Induction
Middle Aged
Combined Modality Therapy
medicine.anatomical_structure
Oncology
Blinatumomab
Female
Immunotherapy
Antibody
medicine.drug
Adult
T cell
Antigens, CD19
Disease-Free Survival
Young Adult
Antigen
Antigens, Neoplasm
Lymphopenia
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
medicine
Humans
Cell Lineage
Aged
Inotuzumab ozogamicin
Chemotherapy
business.industry
Minimal residual disease
Drug Resistance, Neoplasm
Immunology
Cancer research
biology.protein
business
T-Lymphocytes, Cytotoxic
Subjects
Details
- ISSN :
- 15277755
- Volume :
- 29
- Issue :
- 18
- Database :
- OpenAIRE
- Journal :
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology
- Accession number :
- edsair.doi.dedup.....18a5e842b2b8cefd653a3ea264297c06