An open-label, phase I/II trial to determine the maximum tolerated dose and investigate safety, pharmacokinetics and efficacy of BI 836858, an unconjugated anti-CD33 monoclonal antibody, in combination with decitabine in patients with acute myeloid leukemia

• Type of Material: Article
• Authors: Walter Fiedler, Universitätsklinikum Hamburg-Eppendorf; Pau Montesinos, Instituto de Salud Carlos III; Christoph Schliemann, Universitätsklinikum Münster; Jan Middeke, Universitätsklinikum Carl Gustav Carus Dresden; Sumithira Vasu, The Ohio State University Comprehensive Cancer Center; Christian W Scholz, Vivantes Klinikum Am Urban; Jordi Esteve, Universitat de Barcelona; Shoubhik Mondal, Boehringer Ingelheim Pharmaceuticals, Inc.; Björn Rüter, Boehringer Ingelheim Pharma GmbH & Co. KG; Ute Burkard, Boehringer Ingelheim Pharma GmbH & Co. KG; Annika Osswald, Boehringer Ingelheim Pharma GmbH & Co. KG; William Blum, Emory University
• Language: English
• Date: 2022-12-01
• Publisher: Ferrata Storti Foundation
• Publication Version: Final Published Version
• Copyright Statement: © 2022 Ferrata Storti Foundation
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3324/haematol.2022.281128
• Title of Journal or Parent Work: Haematologica
• Volume: 107
• Issue: 12
• Start Page: 2977
• End Page: 2982
• Grant/Funding Information: This work was supported by Boehringer Ingelheim. The sponsor was involved in the study design and the collection, analysis and interpretation of the data. Boehringer Ingelheim was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations. Medical writing support for the development of this manuscript, under the direction of the authors, was provided by Sheridan Henness, and Lynn Pritchard, DPhil, of Ashfield MedComms, an Inizio Company, and was funded by Boehringer Ingelheim.
• Keywords: Decitabine; Antibodies, Monoclonal, Humanized; Humans; Sialic Acid Binding Ig-like Lectin 3; Leukemia, Myeloid, Acute; Antineoplastic Combined Chemotherapy Protocols; Maximum Tolerated Dose
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Oncology

Abstract

Despite significant developments over the last decade, including the emergence of the hypomethylating agents, azacitidine and decitabine, and the bcl-2 antagonist, venetoclax, further treatment options for patients with acute myeloid leukemia (AML) remain an unmet medical need, especially in elderly patients. While hypomethylating agents, alone or in combination with venetoclax, have improved outcomes in elderly patients ineligible for intensive chemotherapy, survival is modest (median overall survival of ~7–15 months in clinical trials).1-3 Regardless of treatment intensity, resistance and relapse to treatment remains a clinical challenge in patients with AML, particularly in elderly patients (>65 years).4