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:

• acute lymphoblastic leukemia
• AMG 103
• bi-specific T-cell engager
• blinatumomab
• non-Hodgkin’s lymphoma

Acknowledgments

M Wetzler contributed significantly to the preparation of this manuscript prior to his unfortunate passing. It is with great reverence that we acknowledge the selfless dedication he had to his practice, research, patients, and the mentorship he provided the authors of this manuscript. B Rogala and CW Freyer contributed equally to the preparation of the manuscript.

Declaration of interest

This manuscript was supported in part by grants from the National Cancer Institute (grant number CA16056) to Roswell Park Cancer Institute, the Szefel Foundation, the Leonard S LuVullo Endowment for Leukemia Research, the Nancy C Cully Endowment for Leukemia Research, the Babcock Family Endowment and the Heidi Leukemia Research Fund, Buffalo, NY. ES Wang is a consultant and principal investigator for Juno and is also supported by a Cancer Clinical Investigator Team Leadership Award (CCITLA) awarded by National Cancer Institute through a supplement to P30CA016056. M Wetzler was a consultant for Amgen and Juno. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.