Advances in the Treatment of Acute Myeloid Leukemia: New Drugs and New Challenges

被引：259

作者：

Short, Nicholas J. ^{[1
]}

Konopleva, Marina ^{[1
]}

Kadia, Tapan M. ^{[1
]}

Borthakur, Gautam ^{[1
]}

Ravandi, Farhad ^{[1
]}

DiNardo, Courtney D. ^{[1
]}

Daver, Naval ^{[1
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA

来源：

CANCER DISCOVERY | 2020年 / 10卷 / 04期

关键词：

ACUTE PROMYELOCYTIC LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; CONSTITUTIVELY ACTIVATED FLT3; GEMTUZUMAB OZOGAMICIN; ARSENIC TRIOXIDE; OLDER PATIENTS; RETINOIC ACID; OPEN-LABEL; COSTIMULATORY MOLECULES; PROMOTES RESISTANCE;

D O I：

10.1158/2159-8290.CD-19-1011

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The therapeutic armamentarium of acute myeloid leukemia (AML) has rapidly expanded in the past few years, driven largely by translational research into its genomic landscape and an improved understanding of mechanisms of resistance to conventional therapies. However, primary and secondary drug resistance remains a substantial problem for most patients. Research into the mechanisms of resistance to these new agents is informing the development of the next class of AML drugs and the design of combination regimens aimed at optimally exploiting therapeutic vulnerabilities, with the ultimate goal of eradicating all subclones of the disease and increasing cure rates in AML. Significance: AML is a heterogeneous disease, characterized by a broad spectrum of molecular alterations that influence clinical outcomes and also provide potential targets for drug development. This review discusses the current and emerging therapeutic landscape of AML, highlighting novel classes of drugs and how our expanding knowledge of mechanisms of resistance are informing future therapies and providing new opportunities for effective combination strategies.

引用

页码：506 / 525

页数：20

共 186 条

[1] The Combination of Quizartinib with Azacitidine or Low Dose Cytarabine Is Highly Active in Patients (Pts) with FLT3-ITD Mutated Myeloid Leukemias: Interim Report of a Phase I/II Trial [J].

Abdelall, Waleed ;

Kantarjian, Hagop M. ;

Borthakur, Gautam ;

Garcia-Manero, Guillermo ;

Patel, Keyur P. ;

Jabbour, Elias J. ;

Daver, Naval G. ;

Kadia, Tapan ;

Gborogen, Rosilyn A. ;

Konopleva, Marina ;

Ravandi, Farhad ;

Andreef, Michael ;

Cortes, Jorge E. .

BLOOD, 2016, 128 (22)

[2] Targeting PIM kinases impairs survival of hematopoietic cells transformed by kinase inhibitor-sensitive and kinase inhibitor-resistant forms of Fms-like tyrosine kinase 3 and BCR/ABL [J].

Adam, M ;

Pogacic, V ;

Bendit, M ;

Chappuis, R ;

Nawijn, MC ;

Duyster, J ;

Fox, CJ ;

Thompson, CB ;

Cools, J ;

Schwaller, J .

CANCER RESEARCH, 2006, 66 (07) :3828-3835

[3] CD47 Blockade by Hu5F9-G4 and Rituximab in Non-Hodgkin's Lymphoma [J].

Advani, Ranjana ;

Flinn, Ian ;

Popplewell, Leslie ;

Forero, Andres ;

Bartlett, Nancy L. ;

Ghosh, Nilanjan ;

Kline, Justin ;

Roschewski, Mark ;

LaCasce, Ann ;

Collins, Graham P. ;

Thu Tran ;

Lynn, Judith ;

Chen, James Y. ;

Volkmer, Jens-Peter ;

Agoram, Balaji ;

Huang, Jie ;

Majeti, Ravindra ;

Weissman, Irving L. ;

Takimoto, Chris H. ;

Chao, Mark P. ;

Smith, Sonali M. .

NEW ENGLAND JOURNAL OF MEDICINE, 2018, 379 (18) :1711-1721

[4] Targeted Conditioning of Iomab-B (131I-anti-CD45) Prior to Allogeneic Hematopoietic Cell Transplantation Versus Conventional Care in Relapsed or Refractory Acute Myeloid Leukemia (AML): Preliminary Feasibility and Safety Results from the Prospective, Randomized Phase 3 Sierra Trial [J].

Agura, Edward ;

Gyurkocza, Boglarka ;

Nath, Rajneesh ;

Litzow, Mark R. ;

Tomlinson, Benjamin K. ;

Abhyankar, Sunil ;

Seropian, Stuart ;

Stiff, Patrick J. ;

Choe, Hannah K. ;

Kebriaei, Partow ;

Foran, James M. ;

Chen, George ;

Levy, Moshe Yair ;

Lazarus, Hillard M. ;

Giralt, Sergio ;

Berger, Mark S. ;

Reddy, Vijay ;

Pagel, John M. .

BLOOD, 2018, 132

[5] Outcomes with Subsequent FLT3-Inhibitor (FLT3i) Based Therapies in FLT3-Mutated (mu) Patients (pts) Refractory/Relapsed (R/R) to One or More Prior FLT3 Inhibitor Based Therapies: A Single Center Experience [J].

Alfayez, Mansour ;

Kantarjian, Hagop M. ;

Ravandi, Farhad ;

Konopleva, Marina Y. ;

Garcia-Manero, Guillermo ;

Kadia, Tapan M. ;

Jabbour, Elias J. ;

Borthakur, Gautam ;

DiNardo, Courtney D. ;

Estrov, Zeev E. ;

Pemmaraju, Naveen ;

Pierce, Sherry A. ;

Yilmaz, Musa E. ;

Short, Nicholas J. ;

Takahashi, Koichi ;

Assi, Rita ;

Andreeff, Michael ;

Cortes, Jorge E. ;

Daver, Naval G. .

BLOOD, 2018, 132

[6] Gemtuzumab Ozogamicin Versus Best Supportive Care in Older Patients With Newly Diagnosed Acute Myeloid Leukemia Unsuitable for Intensive Chemotherapy: Results of the Randomized Phase III EORTC-GIMEMA AML-19 Trial [J].

Amadori, Sergio ;

Suciu, Stefan ;

Selleslag, Dominik ;

Aversa, Franco ;

Gaidano, Gianluca ;

Musso, Maurizio ;

Annino, Luciana ;

Venditti, Adriano ;

Voso, Maria Teresa ;

Mazzone, Carla ;

Magro, Domenico ;

De Fabritiis, Paolo ;

Muus, Petra ;

Alimena, Giuliana ;

Mancini, Marco ;

Hagemeijer, Anne ;

Paoloni, Francesca ;

Vignetti, Marco ;

Fazi, Paola ;

Meert, Liv ;

Ramadan, Safaa Mahmoud ;

Willemze, Roel ;

de Witte, Theo ;

Baron, Frederic .

JOURNAL OF CLINICAL ONCOLOGY, 2016, 34 (09) :972-+

[7] Genetic variegation of clonal architecture and propagating cells in leukaemia [J].

Anderson, Kristina ;

Lutz, Christoph ;

van Delft, Frederik W. ;

Bateman, Caroline M. ;

Guo, Yanping ;

Colman, Susan M. ;

Kempski, Helena ;

Moorman, Anthony V. ;

Titley, Ian ;

Swansbury, John ;

Kearney, Lyndal ;

Enver, Tariq ;

Greaves, Mel .

NATURE, 2011, 469 (7330) :356-+

[8]

[Anonymous], 2019, Cancer Discov, V9, pOF6, DOI 10.1158/2159-8290.CD-NB2019-046

[9]

[Anonymous], 2018, Cancer Discov, V8, pOF2, DOI 10.1158/2159-8290.CD-NB2018-090

[10] Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia: Time to Move Toward a Minimal Residual Disease-Based Definition of Complete Remission? [J].

Araki, Daisuke ;

Wood, Brent L. ;

Othus, Megan ;

Radich, Jerald P. ;

Halpern, Anna B. ;

Zhou, Yi ;

Mielcarek, Marco ;

Estey, Elihu H. ;

Appelbaum, Frederick R. ;

Walter, Roland B. .

JOURNAL OF CLINICAL ONCOLOGY, 2016, 34 (04) :329-+

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