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.

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 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. 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. 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.

Citation

Max S Topp, Peter Kufer, Nicola Gökbuget, Mariele Goebeler, Matthias Klinger, Svenja Neumann, Heinz-A Horst, Thorsten Raff, Andreas Viardot, Mathias Schmid, Matthias Stelljes, Markus Schaich, Evelyn Degenhard, Rudolf Köhne-Volland, Monika Brüggemann, Oliver Ottmann, Heike Pfeifer, Thomas Burmeister, Dirk Nagorsen, Margit Schmidt, Ralf Lutterbuese, Carsten Reinhardt, Patrick A Baeuerle, Michael Kneba, Hermann Einsele, Gert Riethmüller, Dieter Hoelzer, Gerhard Zugmaier, Ralf C Bargou. 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. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2011 Jun 20;29(18):2493-8

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PMID: 21576633

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