The Evolution of Research and Therapy With Hypomethylating Agents in Acute Myeloid Leukemia and Myelodysplastic Syndrome: New Directions for Old Drugs

被引：7

作者：

Short, Nicholas J. ^{[1
]}

Dombret, Herve ^{[2
]}

Ades, Lionel ^{[2
]}

Kantarjian, Hagop ^{[1
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Unit 428,1515 Holcombe Blvd, Houston, TX 77030 USA

[2] Univ Paris, Dept Hematol, St Louis Inst Res, Hop St Louis,AP HP, Paris, France

来源：

CANCER JOURNAL | 2022年 / 28卷 / 01期

关键词：

Azacitidine; decitabine; DNA methyltransferase inhibitors; epigenetics; venetoclax; CONVENTIONAL CARE REGIMENS; RANDOMIZED PHASE-III; LOW-DOSE CYTARABINE; OPEN-LABEL; INTENSIVE CHEMOTHERAPY; 10-DAY DECITABINE; ORAL AZACITIDINE; ELDERLY-PATIENTS; SUPPORTIVE CARE; CANCER;

D O I：

10.1097/PPO.0000000000000568

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Azacitidine and decitabine are cytosine analogs that function as DNA methyltransferase inhibitors. These agents, commonly referred to as "hypomethylating agents," are widely used for the treatment of myelodysplastic syndrome and acute myeloid leukemia (AML). In this review, we discuss the clinical development of these drugs, including the early studies that led to the optimization of their doses and schedules, and the pivotal studies that led to their regulatory approval, both as monotherapy and in combination with venetoclax for older adults with AML who are unfit for intensive chemotherapy. We also review the more recent development of oral hypomethylating agent formulations and the novel oral strategies being developed in myelodysplastic syndrome and AML.

引用

页码：29 / 36

页数：8

共 59 条

[1] Ten-day decitabine as initial therapy for newly diagnosed patients with acute myeloid leukemia unfit for intensive chemotherapy [J].

Bhatnagar, Bhavana ;

Duong, Vu H. ;

Gourdin, Theodore S. ;

Tidwell, Michael L. ;

Chen, Ching ;

Ning, Yi ;

Emadi, Ashkan ;

Sausville, Edward A. ;

Baer, Maria R. .

LEUKEMIA & LYMPHOMA, 2014, 55 (07) :1533-1537

[2] Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine [J].

Blum, William ;

Garzon, Ramiro ;

Klisovic, Rebecca B. ;

Schwind, Sebastian ;

Walker, Alison ;

Geyer, Susan ;

Liu, Shujun ;

Havelange, Violaine ;

Becker, Heiko ;

Schaaf, Larry ;

Mickle, Jon ;

Devine, Hollie ;

Kefauver, Cheryl ;

Devine, Steven M. ;

Chan, Kenneth K. ;

Heerema, Nyla A. ;

Bloomfield, Clara D. ;

Grever, Michael R. ;

Byrd, John C. ;

Villalona-Calero, Miguel ;

Croce, Carlo M. ;

Marcucci, Guido .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (16) :7473-7478

[3] A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fit for intensive treatment [J].

Burnett, Alan K. ;

Milligan, Donald ;

Prentice, Archie G. ;

Goldstone, Anthony H. ;

McMullin, Mary F. ;

Hills, Robert K. ;

Wheatley, Keith .

CANCER, 2007, 109 (06) :1114-1124

[4]

Daver N, 2020, Blood, V136, P17

[5] Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia [J].

DiNardo, C. D. ;

Jonas, B. A. ;

Pullarkat, V. ;

Thirman, M. J. ;

Garcia, J. S. ;

Wei, A. H. ;

Konopleva, M. ;

Doehner, H. ;

Letai, A. ;

Fenaux, P. ;

Koller, E. ;

Havelange, V. ;

Leber, B. ;

Esteve, J. ;

Wang, J. ;

Pejsa, V. ;

Hajek, R. ;

Porkka, K. ;

Illes, A. ;

Lavie, D. ;

Lemoli, R. M. ;

Yamamoto, K. ;

Yoon, S. -S. ;

Jang, J. -H. ;

Yeh, S. -P. ;

Turgut, M. ;

Hong, W. -J. ;

Zhou, Y. ;

Potluri, J. ;

Pratz, K. W. .

NEW ENGLAND JOURNAL OF MEDICINE, 2020, 383 (07) :617-629

[6] 10-day decitabine with venetoclax for newly diagnosed intensive chemotherapy ineligible, and relapsed or refractory acute myeloid leukaemia: a single-centre, phase 2 trial [J].

DiNardo, Courtney D. ;

Maiti, Abhishek ;

Rausch, Caitlin R. ;

Pemmaraju, Naveen ;

Naqvi, Kiran ;

Daver, Naval G. ;

Kadia, Tapan M. ;

Borthakur, Gautam ;

Ohanian, Maro ;

Alvarado, Yesid ;

Issa, Ghayas C. ;

Montalban-Bravo, Guillermo ;

Short, Nicholas J. ;

Yilmaz, Musa ;

Bose, Prithviraj ;

Jabbour, Elias J. ;

Takahashi, Koichi ;

Burger, Jan A. ;

Garcia-Manero, Guillermo ;

Jain, Nitin ;

Kornblau, Steven M. ;

Thompson, Philip A. ;

Estrov, Zeev ;

Masarova, Lucia ;

Sasaki, Koji ;

Verstovsek, Srdan ;

Ferrajoli, Alessandra ;

Weirda, William G. ;

Wang, Sa A. ;

Konoplev, Sergej ;

Chen, Zhining ;

Pierce, Sherry A. ;

Ning, Jing ;

Qiao, Wei ;

Ravandi, Farhad ;

Andreeff, Michael ;

Welch, John S. ;

Kantarjian, Hagop M. ;

Konopleva, Marina Y. .

LANCET HAEMATOLOGY, 2020, 7 (10) :E724-E736

[7] Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia [J].

DiNardo, Courtney D. ;

Pratz, Keith ;

Pullarkat, Vinod ;

Jonas, Brian A. ;

Arellano, Martha ;

Becker, Pamela S. ;

Frankfurt, Olga ;

Konopleva, Marina ;

Wei, Andrew H. ;

Kantarjian, Hagop M. ;

Xu, Tu ;

Hong, Wan-Jen ;

Chyla, Brenda ;

Potluri, Jalaja ;

Pollyea, Daniel A. ;

Letai, Anthony .

BLOOD, 2019, 133 (01) :7-17

[8] Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study [J].

DiNardo, Courtney L. ;

Pratz, Keith W. ;

Letai, Anthony ;

Jonas, Brian A. ;

Wei, Andrew H. ;

Thirman, Michael ;

Arellano, Martha ;

Frattini, Mark G. ;

Kantarjian, Hagop ;

Popovic, Relja ;

Chyla, Brenda ;

Xu, Tu ;

Dunbar, Martin ;

Agarwal, Suresh K. ;

Humerickhouse, Rod ;

Mabry, Mack ;

Potluri, Jalaja ;

Konopleva, Marina ;

Pollyea, Daniel A. .

LANCET ONCOLOGY, 2018, 19 (02) :216-228

[9] International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts [J].

Dombret, Herve ;

Seymour, John F. ;

Butrym, Aleksandra ;

Wierzbowska, Agnieszka ;

Selleslag, Dominik ;

Jang, Jun Ho ;

Kumar, Rajat ;

Cavenagh, James ;

Schuh, Andre C. ;

Candoni, Anna ;

Recher, Christian ;

Sandhu, Irwindeep ;

Bernal del Castillo, Teresa ;

Al-Ali, Haifa Kathrin ;

Martinelli, Giovanni ;

Falantes, Jose ;

Noppeney, Richard ;

Stone, Richard M. ;

Minden, Mark D. ;

McIntyre, Heidi ;

Songer, Steve ;

Lucy, Lela M. ;

Beach, C. L. ;

Doehner, Hartmut .

BLOOD, 2015, 126 (03) :291-299

[10] Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study [J].

Fenaux, Pierre ;

Mufti, Ghulam J. ;

Hellstrom-Lindberg, Eva ;

Santini, Valeria ;

Finelli, Carlo ;

Giagounidis, Aristoteles ;

Schoch, Robert ;

Gattermann, Norbert ;

Sanz, Guillermo ;

List, Alan ;

Gore, Steven D. ;

Seymour, John F. ;

Bennett, John M. ;

Byrd, John ;

Backstrom, Jay ;

Zimmerman, Linda ;

McKenzie, David ;

Beach, C. L. ;

Silverman, Lewis R. .

LANCET ONCOLOGY, 2009, 10 (03) :223-232

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