Venetoclax-based salvage therapy in patients with relapsed/refractory acute myeloid leukemia previously treated with FLT3 or IDH1/2 inhibitors

被引:10
作者
Bewersdorf, Jan Philipp [1 ]
Shallis, Rory M. [2 ,3 ]
Derkach, Andriy [4 ]
Goldberg, Aaron D. [1 ]
Stein, Anthony [5 ]
Stein, Eytan M. [1 ]
Marcucci, Guido [5 ]
Zeidan, Amer M. [2 ,3 ]
Shimony, Shai [6 ]
DeAngelo, Daniel J. [6 ]
Stone, Richard M. [6 ]
Aldoss, Ibrahim [5 ]
Ball, Brian J. [5 ]
Stahl, Maximilian [6 ]
机构
[1] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, 1275 York Ave, New York, NY 10021 USA
[2] Yale Univ, New Haven, CT USA
[3] Yale Canc Ctr, New Haven, CT USA
[4] Mem Sloan Kettering Canc Ctr, Dept Biostat & Epidemiol, 1275 York Ave, New York, NY 10021 USA
[5] City Hope Natl Med Ctr, 1500 E Duarte Rd, Duarte, CA 91010 USA
[6] Dana Farber Canc Inst, Div Leukemia, Dept Med Oncol, Boston, MA 02115 USA
基金
美国国家卫生研究院;
关键词
Acute myeloid leukemia; AML; targeted agents; venetoclax; outcomes; AZACITIDINE; COMBINATION;
D O I
10.1080/10428194.2022.2136952
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
FLT3, IDH1 and IDH2 inhibitors as well as venetoclax in combination with hypomethylating agents or low-dose cytarabine have expanded treatment options for patients with acute myeloid leukemia (AML). However, little data exist on the efficacy of venetoclax-based therapies in AML patients previously treated with FLT3 or IDH1/2 inhibitors. In this multicenter, retrospective cohort study, we included 44 patients who received venetoclax-based therapy after FLT3, IDH1 or IDH2 inhibitors. The overall response rate (ORR; composite of complete remission [CR]/CR with incomplete count recovery, partial remission, and morphologic leukemia free state) was 56.8% (18.2% CR) and a median overall survival of 9.2 months. While 6 out of 7 patients with IDH1 mutations who had previously been treated with ivosidenib responded to venetoclax-based therapy, FLT3-ITD mutations were associated with a lower response rate. Our data suggest that venetoclax can be an effective salvage therapy in patients previously treated with IDH1/2 or FLT3 inhibitors.
引用
收藏
页码:188 / 196
页数:9
相关论文
共 18 条
[1]   The propriety of upgrading responses to venetoclax plus azacitidine in newly diagnosed patients with acute myeloid leukemia [J].
Abbott, Diana ;
Cherry, Evan ;
Amaya, Maria ;
McMahon, Christine ;
Schwartz, Marc ;
Winters, Amanda ;
Schowinsky, Jeffrey ;
Jordan, Craig T. ;
Smith, Clayton ;
Gutman, Jonathan A. ;
Pollyea, Daniel A. .
LEUKEMIA & LYMPHOMA, 2021, 62 (06) :1466-1473
[2]   Venetoclax-based combinations in AML and high-risk MDS prior to and following allogeneic hematopoietic cell transplant [J].
Bewersdorf, Jan Philipp ;
Derkach, Andriy ;
Gowda, Lohith ;
Menghrajani, Kamal ;
DeWolf, Susan ;
Ruiz, Josel D. ;
Ponce, Doris M. ;
Shaffer, Brian C. ;
Tamari, Roni ;
Young, James W. ;
Jakubowski, Ann A. ;
Gyurkocza, Boglarka ;
Chan, Alexander ;
Xiao, Wenbin ;
Glass, Jacob ;
King, Amber C. ;
Cai, Sheng F. ;
Daniyan, Anthony ;
Famulare, Christopher ;
Cuello, Bernadette M. ;
Podoltsev, Nikolai A. ;
Roshal, Mikhail ;
Giralt, Sergio ;
Perales, Miguel-Angel ;
Seropian, Stuart ;
Cho, Christina ;
Zeidan, Amer M. ;
Prebet, Thomas ;
Stein, Eytan M. ;
Tallman, Martin S. ;
Goldberg, Aaron D. ;
Stahl, Maximilian .
LEUKEMIA & LYMPHOMA, 2021, 62 (14) :3394-3401
[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]   How I treat relapsed or refractory AML [J].
DeWolf, Susan ;
Tallman, Martin S. .
BLOOD, 2020, 136 (09) :1023-1032
[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]   Molecular patterns of response and treatment failure after frontline venetoclax combinations in older patients with AML [J].
DiNardo, C. D. ;
Tiong, I. S. ;
Quaglieri, A. ;
MacRaild, S. ;
Loghavi, S. ;
Brown, F. C. ;
Thijssen, R. ;
Pomilio, G. ;
Ivey, A. ;
Salmon, J. M. ;
Glytsou, C. ;
Fleming, S. A. ;
Zhang, Q. ;
Ma, H. ;
Patel, K. P. ;
Kornblau, S. M. ;
Xu, Z. ;
Chua, C. C. ;
Chen, Xufeng ;
Blombery, P. ;
Flensburg, C. ;
Cummings, N. ;
Aifantis, I. ;
Kantarjian, H. ;
Huang, D. C. S. ;
Roberts, A. W. ;
Majewski, I. J. ;
Konopleva, M. ;
Wei, A. H. .
BLOOD, 2020, 135 (11) :791-803
[7]   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
[8]   How I treat acute myeloid leukemia in the era of new drugs [J].
DiNardo, Courtney D. ;
Wei, Andrew H. .
BLOOD, 2020, 135 (02) :85-96
[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]   Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel [J].
Doehner, Hartmut ;
Estey, Elihu ;
Grimwade, David ;
Amadori, Sergio ;
Appelbaum, Frederick R. ;
Buechner, Thomas ;
Dombret, Herve ;
Ebert, Benjamin L. ;
Fenaux, Pierre ;
Larson, Richard A. ;
Levine, Ross L. ;
Lo-Coco, Francesco ;
Naoe, Tomoki ;
Niederwieser, Dietger ;
Ossenkoppele, Gert J. ;
Sanz, Miguel ;
Sierra, Jorge ;
Tallman, Martin S. ;
Tien, Hwei-Fang ;
Wei, Andrew H. ;
Lowenberg, Bob ;
Bloomfield, Clara D. .
BLOOD, 2017, 129 (04) :424-447