TY - JOUR
T1 - Immune therapies in acute myeloid leukemia
T2 - A focus on monoclonal antibodies and immune checkpoint inhibitors
AU - Assi, Rita
AU - Kantarjian, Hagop
AU - Ravandi, Farhad
AU - Daver, Naval
N1 - Funding Information:
H.K. has received research funding from BMS, Pfizer and served as a consultant for Pfizer, Immunogen. F.R. has received research funding from Seattle Genetics, Amgen, Macrogenics, and served as a consultant for Seattle Genetics and Amgen. N.D. has received research funding from BMS, Pfizer, Merck and served as a consultant for BMS, Pfizer, Immunogen, and Celgene. This study was supported in part by the MD Anderson Cancer Centre Support Grant (CCSG) CA016672, the MD Anderson Cancer Center Leukemia SPORE CA100632, the Charif Souki Cancer Research Fund and generous philanthropic contributions to the MD Anderson Moon Shots Program.
Publisher Copyright:
© 2018 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - Purpose of review This review discusses the rationale, efficacy, and toxicity of a variety of immune approaches being evaluated in the therapy of acute myeloid leukemia (AML) including naked and conjugated monoclonal antibodies, bispecific T-cell engager antibodies, and immune checkpoint blockade via antibodies targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed-death 1 (PD-1). Recent findings The stellar success of immune therapies that harness the power of T cells in solid tumors and an improved understanding of the immune system in patients with hematologic malignancies have resulted in major efforts to develop immune therapies for the treatment of patients with AML. Monoclonal antibodies in AML therapy include naked antibodies against AML surface antigens such as CD33 (e.g. lintuzumab) or CD38 (e.g. daratumumab), antibodies conjugated to toxins in various anti-CD33 (gemtuzumab ozogamicin, SGN33A, IMGN779) and anti-CD123 (SL-401, SGN-CD123A) formulations, and antibodies conjugated to radioactive particles such as 131 I or 225 Ac-labeled anti-CD33 or anti-CD45 antibodies. Additional antigenic targets of interest in AML include CLL1, CD38, CD25, TIM3, FLT3, and others. Approaches to harness the body's own T cells against AML include antibodies that recruit and induce cytotoxicity of tumor cells by T cells (bispecific T-cell engager [BiTE] such as CD33 x CD3 (e.g. AMG 330) or CD123 x CD3 (e.g. flotetuzumab, JNJ-63709178) or antibodies that block immune checkpoint receptors CTLA4 (e.g. ipilimumab) or PD1/PD-L1 (e.g. nivolumab, pembrolizumab, avelumab) on T cells, unleashing the patients' T cells against leukemic cells. Summary The ongoing trials and well designed correlative interrogation of the immune system in patients treated on such trials will further enhance our understanding and clinical application of immune therapies as single-agent and combination approaches for the treatment of AML.
AB - Purpose of review This review discusses the rationale, efficacy, and toxicity of a variety of immune approaches being evaluated in the therapy of acute myeloid leukemia (AML) including naked and conjugated monoclonal antibodies, bispecific T-cell engager antibodies, and immune checkpoint blockade via antibodies targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed-death 1 (PD-1). Recent findings The stellar success of immune therapies that harness the power of T cells in solid tumors and an improved understanding of the immune system in patients with hematologic malignancies have resulted in major efforts to develop immune therapies for the treatment of patients with AML. Monoclonal antibodies in AML therapy include naked antibodies against AML surface antigens such as CD33 (e.g. lintuzumab) or CD38 (e.g. daratumumab), antibodies conjugated to toxins in various anti-CD33 (gemtuzumab ozogamicin, SGN33A, IMGN779) and anti-CD123 (SL-401, SGN-CD123A) formulations, and antibodies conjugated to radioactive particles such as 131 I or 225 Ac-labeled anti-CD33 or anti-CD45 antibodies. Additional antigenic targets of interest in AML include CLL1, CD38, CD25, TIM3, FLT3, and others. Approaches to harness the body's own T cells against AML include antibodies that recruit and induce cytotoxicity of tumor cells by T cells (bispecific T-cell engager [BiTE] such as CD33 x CD3 (e.g. AMG 330) or CD123 x CD3 (e.g. flotetuzumab, JNJ-63709178) or antibodies that block immune checkpoint receptors CTLA4 (e.g. ipilimumab) or PD1/PD-L1 (e.g. nivolumab, pembrolizumab, avelumab) on T cells, unleashing the patients' T cells against leukemic cells. Summary The ongoing trials and well designed correlative interrogation of the immune system in patients treated on such trials will further enhance our understanding and clinical application of immune therapies as single-agent and combination approaches for the treatment of AML.
KW - bi-specific antibodies
KW - immune checkpoint inhibitors
KW - immunotherapy
KW - monoclonal antibodies
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U2 - 10.1097/MOH.0000000000000401
DO - 10.1097/MOH.0000000000000401
M3 - Review article
C2 - 29206680
AN - SCOPUS:85042435982
SN - 1065-6251
VL - 25
SP - 136
EP - 145
JO - Current opinion in hematology
JF - Current opinion in hematology
IS - 2
ER -