Hypomethylating agents with venetoclax: have we discovered the holy grail?

被引:3
作者
Gutman, Jonathan A. [1 ]
Pollyea, Daniel A. [1 ]
机构
[1] Univ Colorado, Sch Med, Dept Med, Div Hematol, Aurora, CO USA
关键词
acute myeloid leukaemia; hypomethylating agent; leukemia stem cell; venetoclax; ACUTE MYELOID-LEUKEMIA; COOPERATIVE-ONCOLOGY-GROUP; ACUTE MYELOGENOUS LEUKEMIA; OXIDATIVE-PHOSPHORYLATION; STEM-CELLS; AZACITIDINE; THERAPY; EXPERIENCE;
D O I
10.1097/MOH.0000000000000560
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Purpose of review Since its approval in November 2018, venetoclax with a hypomethylating agent backbone has shown promising efficacy for older, newly diagnosed acute myeloid leukemia (AML) patients who are unfit for standard intensive induction chemotherapy. This regimen is well tolerated, allows for deep and durable responses and may be increasing the prevalence of the disease. Although there is justifiable excitement, it remains to be seen to what extent venetoclax-based regimens, as they are currently administered, will have a long-term impact on the treatment of AML. This review aims to evaluate the strengths of the regimen that deserve enthusiasm as well as its shortcomings, which should be viewed as opportunities for improvement. Recent findings The clinical efficacy as well as the novel mechanism of venetoclax with hypomethylating agents will be described here. Venetoclax with hypomethylating agents do not represent the holy grail for AML, but this regimen is a promising step in the right direction, and proof of principle that a low-intensity therapy can have a major impact on this disease.
引用
收藏
页码:76 / 80
页数:5
相关论文
共 36 条
[1]   Efficacy of the combination of venetoclax and hypomethylating agents in relapsed/refractory acute myeloid leukemia [J].
Aldoss, Ibrahim ;
Yang, Dongyun ;
Aribi, Ahmed ;
Ali, Haris ;
Sandhu, Karamjeet ;
Al Malki, Monzr M. ;
Mei, Matthew ;
Salhotra, Amandeep ;
Khaled, Samer ;
Nakamura, Ryotaro ;
Snyder, David ;
O'Donnell, Margaret ;
Stein, Anthony S. ;
Forman, Stephen J. ;
Marcucci, Guido ;
Pullarkat, Vinod .
HAEMATOLOGICA, 2018, 103 (09) :E404-E407
[2]  
BENNETT JM, 1981, CANCER RES, V41, P4833
[3]  
CHAMPLIN R, 1987, BLOOD, V69, P1551
[4]   Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML [J].
DiNardo, C. D. ;
Stein, E. M. ;
de Botton, S. ;
Roboz, G. J. ;
Altman, J. K. ;
Mims, A. S. ;
Swords, R. ;
Collins, R. H. ;
Mannis, G. N. ;
Pollyea, D. A. ;
Donnellan, W. ;
Fathi, A. T. ;
Pigneux, A. ;
Erba, H. P. ;
Prince, G. T. ;
Stein, A. S. ;
Uy, G. L. ;
Foran, J. M. ;
Traer, E. ;
Stuart, R. K. ;
Arellano, M. L. ;
Slack, J. L. ;
Sekeres, M. A. ;
Willekens, C. ;
Choe, S. ;
Wang, H. ;
Zhang, V. ;
Yen, K. E. ;
Kapsalis, S. M. ;
Yang, H. ;
Dai, D. ;
Fan, B. ;
Goldwasser, M. ;
Liu, H. ;
Agresta, S. ;
Wu, B. ;
Attar, E. C. ;
Tallman, M. S. ;
Stone, R. M. ;
Kantarjian, H. M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2018, 378 (25) :2386-2398
[5]   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
[6]   Clinical experience with the BCL2-inhibitor venetoclax in combination therapy for relapsed and refractory acute myeloid leukemia and related myeloid malignancies [J].
DiNardo, Courtney D. ;
Rausch, Caitlin R. ;
Benton, Christopher ;
Kadia, Tapan ;
Jain, Nitin ;
Pemmaraju, Naveen ;
Daver, Naval ;
Covert, Wendy ;
Marx, Kayleigh R. ;
Mace, Morgan ;
Jabbour, Elias ;
Cortes, Jorge ;
Garcia-Manero, Guillermo ;
Ravandi, Farhad ;
Bhalla, Kapil N. ;
Kantarjian, Hagop ;
Konopleva, Marina .
AMERICAN JOURNAL OF HEMATOLOGY, 2018, 93 (03) :401-407
[7]   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
[8]   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
[9]  
Gilliland D Gary, 2004, Hematology Am Soc Hematol Educ Program, P80
[10]   Imp2 controls oxidative phosphorylation and is crucial for preserving glioblastoma cancer stem cells [J].
Janiszewska, Michalina ;
Suva, Mario L. ;
Riggi, Nicolo ;
Houtkooper, Riekelt H. ;
Auwerx, Johan ;
Clement-Schatlo, Virginie ;
Radovanovic, Ivan ;
Rheinbay, Esther ;
Provero, Paolo ;
Stamenkovic, Ivan .
GENES & DEVELOPMENT, 2012, 26 (17) :1926-1944