Blinatumomab: enlisting serial killer T-cells in the war against hematologic malignancies

Abstract

Introduction: The approval of blinatumomab signals the long awaited arrival of immunotherapy for acute lymphoblastic leukemia (ALL). Previous options for relapsed or refractory disease were restricted to cytotoxic chemotherapy with limited efficacy and significant toxicity. Through an innovative mechanism of action, blinatumomab stimulates a polyclonal antitumor T-cell response, yielding unprecedented single agent efficacy in the relapsed/refractory setting. Success comes at the cost of immunological toxicities rarely encountered with previous therapies and challenging administration logistics requiring clinical expertise.

Areas covered: All published clinical and preclinical studies using blinatumomab were reviewed in addition to all registered ongoing clinical trials and data published in abstract form. The search was limited to the English language. The pharmacology, clinical efficacy, toxicity profile, and logistical considerations for drug administration are discussed.

Expert opinion: Blinatumomab is an exciting addition to the treatment armamentarium for relapsed/refractory ALL, yet several questions remain regarding optimal implementation into the current treatment paradigm. A unique toxicity profile should be weighed against promising benefits in a poor prognosis population. Other emerging therapies, such as chimeric antigen receptor-modified T-cells and inotuzumab ozogamicin, with different side effect profiles and administration schedules, may prove to be more beneficial for specific patient populations.

Keywords: AMG 103; acute lymphoblastic leukemia; bi-specific T-cell engager; blinatumomab; non-Hodgkin’s lymphoma.

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