Outcomes of Adults With Relapsed/Refractory Acute Myeloid Leukemia Treated With Venetoclax Plus Hypomethylating Agents at a Comprehensive Cancer Center

被引：43

作者：

Tenold, Matthew E. ^{[1
]}

Moskoff, Benjamin N. ^{[2
]}

Benjamin, David J. ^{[3
]}

Hoeg, Rasmus T. ^{[1
]}

Rosenberg, Aaron S. ^{[1
]}

Abedi, Mehrdad ^{[1
]}

Tuscano, Joseph M. ^{[1
,4
]}

Jonas, Brian A. ^{[1
,4
]}

机构：

[1] Univ Calif Davis, Sch Med, Dept Internal Med, Div Hematol & Oncol, Sacramento, CA 95817 USA

[2] Univ Calif Davis, Sch Med, Dept Pharm, Sacramento, CA 95817 USA

[3] Univ Calif, Irvine Med Ctr, Dept Internal Med, Div Hematol & Oncol, Orange, CA USA

[4] Vet Adm Northern Calif Healthcare Syst, Sacramento, CA USA

来源：

FRONTIERS IN ONCOLOGY | 2021年 / 11卷

关键词：

acute myeloid leukemia; venetoclax (BCL-2 inhibitor); hypomethylating agent; relapsed; refractory; real-world data;

D O I：

10.3389/fonc.2021.649209

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Relapsed/refractory acute myeloid leukemia (AML) is a devastating disease with a poor prognosis and represents a major unmet medical need. We report on a real-world academic center experience of treating 25 patients with relapsed/refractory AML using venetoclax in combination with decitabine or azacitidine, which is not otherwise widely evaluated in the current literature. Our patients come from a large, socioeconomically and geographically diverse area including the majority of Northern California. Most had ELN Adverse Risk (52%) or Intermediate Risk (44%) AML, and most had an ECOG Performance Status of 1 (64%). Over half (52%) had prior hypomethylating agent exposure, and 40% had Secondary AML. We observed an overall response rate of 52%, with eight patients (32%) achieving composite complete remission. Median overall survival was 5.5 months, and for patients achieving composite complete remission this was 21.6 months. One-year estimated overall survival was 38%. Three patients were able to proceed directly to stem cell transplant for consolidation, and all three were alive at last follow-up, ranging 13.8-24.0 months. We found venetoclax in combination with hypomethylating agents to be well tolerated and potentially efficacious in securing long-term remissions for patients with relapsed/refractory AML.

引用

页数：6

共 19 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] Age and acute myeloid leukemia [J].

Appelbaum, FR ;

Gundacker, H ;

Head, DR ;

Slovak, ML ;

Willman, CL ;

Godwin, JE ;

Anderson, JE ;

Petersdorf, SH .

BLOOD, 2006, 107 (09) :3481-3485

[3] Venetoclax as monotherapy and in combination with hypomethylating agents or low dose cytarabine in relapsed and treatment refractory acute myeloid leukemia: a systematic review and meta-analysis [J].

Bewersdorf, Jan Philipp ;

Giri, Smith ;

Wang, Rong ;

Williams, Robert T. ;

Tallman, Martin S. ;

Zeidan, Amer M. ;

Stahl, Maximilian .

HAEMATOLOGICA, 2020, 105 (11) :2659-2663

[4] BCL-2 family proteins as 5-Azacytidine-sensitizing targets and determinants of response in myeloid malignancies [J].

Bogenberger, J. M. ;

Kornblau, S. M. ;

Pierceall, W. E. ;

Lena, R. ;

Chow, D. ;

Shi, C-X ;

Mantei, J. ;

Ahmann, G. ;

Gonzales, I. M. ;

Choudhary, A. ;

Valdez, R. ;

Camoriano, J. ;

Fauble, V. ;

Tiedemann, R. E. ;

Qiu, Y. H. ;

Coombes, K. R. ;

Cardone, M. ;

Braggio, E. ;

Yin, H. ;

Azorsa, D. O. ;

Mesa, R. A. ;

Stewart, A. K. ;

Tibes, R. .

LEUKEMIA, 2014, 28 (08) :1657-1665

[5] Changes in Cytogenetics and Molecular Genetics in Acute Myeloid Leukemia From Childhood to Adult Age Groups [J].

Creutzig, Ursula ;

Zimmermann, Martin ;

Reinhardt, Dirk ;

Rasche, Mareike ;

von Neuhoff, Christine ;

Alpermann, Tamara ;

Dworzak, Michael ;

Perglerova, Karolina ;

Zemanova, Zuzana ;

Tchinda, Joelle ;

Bradtke, Jutta ;

Thiede, Christian ;

Haferlach, Claudia .

CANCER, 2016, 122 (24) :3821-3830

[6] 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

[7] 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

[8] 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

[9] 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

[10] 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

← 1 2 →