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An Update on the Clinical Evaluation of Antibody-Based Therapeutics in Acute Myeloid Leukemia

  • Acute Myeloid Leukemias (U Borate, Section Editor)
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Abstract

Purpose of Review

The advent of several targeted agents has revolutionized the treatment of acute myeloid leukemia (AML) in recent times; however, majority of patients are still not cured. In the ongoing quest for rationally targeted treatment strategies in AML, scientific endeavors have focused on identifying new antigen targets on the leukemic cells for therapeutic exploitation including strategies to directly deliver toxins into the leukemic blasts as well as strategies that harness host immunity to favorably impact clinical outcomes. Gemtuzumab ozogamicin, a CD33 directed antibody-drug conjugate, has provided the proof of concept for the potential efficacy of monoclonal antibody-based therapies in AML. This article provides an overview of immunologically relevant antigen targets expressed on the leukemic cells and synopsizes the clinical results evaluating targeted antibody-based therapeutic approach in AML.

Recent Findings

AML blasts and leukemic stem cells express several antigens, including CD33, CD47, CD70, CD123, and CLEC12A. The past several years have seen the burgeoning of cell-specific immunotherapy concepts, including checkpoint inhibitors, antibody–toxin conjugates, and bispecific antibodies in the treatment of AML. The first-in-class anti-CD47 antibody magrolimab and anti-CD70 antibody cusatuzumab in combination with hypomethylating agent (HMA) azacitidine, in newly diagnosed AML, and flotetuzumab, a bispecific DART® (dual-affinity retargeting) antibody to CD3ε and CD123 as salvage option in relapsed/refractory AML appear promising.

Summary

The development of antibody-based immunotherapeutic approach in AML has been encouraging. Ongoing research will define the choice of an appropriate complementary therapeutic agent in antibody-based combination therapy, and whether one or more than one antigen should be simultaneously targeted. Further studies will likely refine the role of antibody-based therapy in post hematopoietic cell transplant setting.

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Funding

Dr. Ravandi has received research funding from Amgen, Macrogenics, Xencor, Taiho, Astex, Abbvie and has been member of advisory boards with Amgen, Xencor, Celgene, BMS, AstraZeneca, Syros, Taiho, Novartis, Astellas, Agios, Innate Pharma.

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  1. Department of Leukemia, The University of Texas – MD Anderson Cancer Center, Houston, TX, USA

    Sangeetha Venugopal, Naval Daver & Farhad Ravandi

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  1. Sangeetha Venugopal
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  2. Naval Daver
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Correspondence to Farhad Ravandi.

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Venugopal, S., Daver, N. & Ravandi, F. An Update on the Clinical Evaluation of Antibody-Based Therapeutics in Acute Myeloid Leukemia. Curr Hematol Malig Rep 16, 89–96 (2021). https://doi.org/10.1007/s11899-021-00612-w

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