Azacitidine and venetoclax with or without pevonedistat in patients with newly diagnosed acute myeloid leukemia

被引：0

作者：

Short, Nicholas J. ^{[1
]}

Wierzbowska, Agnieszka ^{[2
]}

Cluzeau, Thomas ^{[3
]}

Laribi, Kamel ^{[4
]}

Recher, Christian ^{[5
]}

Czyz, Jaroslaw ^{[6
,7
]}

Ochrem, Bogdan ^{[8
]}

Ades, Lionel ^{[9
]}

Gallego-Hernanz, Maria Pilar ^{[10
]}

Heiblig, Mael ^{[11
]}

Audisio, Ernesta ^{[12
]}

Zarzycka, Ewa ^{[13
]}

Li, Shuli ^{[14
]}

Ferenc, Nicholas ^{[14
]}

Yeh, Tammie ^{[14
]}

Faller, Douglas V. ^{[14
]}

Sedarati, Farhad ^{[14
]}

Papayannidis, Cristina ^{[15
]}

机构：

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

[2] Med Univ Lodz, Dept Hematol, Lodz, Poland

[3] Cote Azur Univ, Ctr Hosp Univ Nice CHU, Dept Hematol, Nice, France

[4] Ctr Hosp Mans, Dept Hematol, Le Mans, France

[5] Univ Toulouse, Univ Paul Sabatier Toulouse 3, Inst Univ Canc Toulouse Oncopole, Toulouse, France

[6] Szpital Uniwersytecki 2, Bydgoszcz, Poland

[7] Nicolaus Copernicus Univ Torun, Dept Hematol, Coll Medicum Bydgoszcz, Bydgoszcz, Poland

[8] Univ Hosp, Dept Hematol, Krakow, Poland

[9] Hop St Louis, AP HP, Dept Hematol & Immunol, Paris, France

[10] CHU Miletrie, Dept Hematol, Poitiers, France

[11] Hop Lyon Sud, Serv Hematol Clin, Hosp Civils Lyon, Lyon, France

[12] Haematol Dept, SC Ematol 2, Turin, Italy

[13] Med Univ Gdansk, Dept Hematol & Transplantol, Gdansk, Poland

[14] Inc TDCA, Takeda Dev Ctr Amer, Lexington, MA USA

[15] Ist Ematol Seragnoli, IRCCS Azienda Osped Univ Bologna, Bologna, Italy

来源：

LEUKEMIA & LYMPHOMA | 2025年 / 66卷 / 03期

关键词：

Acute myeloid leukemia; azacitidine; pevonedistat; phase; 2; venetoclax; OLDER PATIENTS; NEDD8-ACTIVATING ENZYME; AML; RECOMMENDATIONS; INHIBITOR; CARE;

D O I：

10.1080/10428194.2024.2431878

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

This phase 2 study investigated pevonedistat + azacitidine + venetoclax (n = 83) versus azacitidine + venetoclax (n = 81) in patients with newly diagnosed acute myeloid leukemia (AML) ineligible for intensive chemotherapy. The study was stopped early following negative results from PANTHER, which evaluated pevonedistat in higher-risk myelodysplastic syndromes/chronic myelomonocytic leukemia or low-blast AML. Outcomes were analyzed up to the datacut. For pevonedistat + azacitidine + venetoclax versus azacitidine + venetoclax, the median follow-up was 8.44 versus 7.95 months; the complete remission (CR) rate was 45% versus 49%; composite CR (CCR; CR+CR with incomplete blood count recovery) was 77% versus 72%. There were no differences in event-free survival (primary endpoint; hazard ratio [HR]: 0.99; 95% confidence interval [CI]: 0.61-1.60; p = 0.477) or overall survival (HR: 1.42; 95% CI: 0.82-2.49; p = 0.896). In exploratory analyses in IDH-mutated AML, CCR rates were higher with pevonedistat + azacitidine + venetoclax versus azacitidine + venetoclax. Safety was similar between treatment arms. Efficacy/safety with azacitidine + venetoclax was consistent with the phase 3 VIALE-A study.Trial registrationNCT04266795

引用

页码：458 / 468

页数：11

共 50 条

[31] Pevonedistat and azacitidine upregulate NOXA (PMAIP1) to increase sensitivity to venetoclax in preclinical models of acute myeloid leukemia
Cojocari, Dan
Smith, Brianna N.
Purkal, Julie J.
Arrate, Maria P.
Huska, Jason D.
Xiao, Yu
Gorska, Agnieszka
Hogdal, Leah J.
Ramsey, Haley E.
Boghaert, Erwin R.
Phillips, Darren C.
Savona, Michael R.
HAEMATOLOGICA, 2022, 107 (04) : 825 - 835
[32] Venetoclax for the treatment of newly diagnosed acute myeloid leukemia in patients who are ineligible for intensive chemotherapy
Richard-Carpentier, Guillaume
DiNardo, Courtney D.
THERAPEUTIC ADVANCES IN HEMATOLOGY, 2019, 10
[33] VENETOCLAX, AZACITIDINE, COMBINED WITH LOW-DOSE CYTARABINE IMPROVE THE REMISSION RATE IN OLDER OR UNFIT PATIENTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA
Han, Xiao
Song, Qingxiao
Wan, Kai
Zhang, Mengyun
Liu, Xue
Yan, Hongju
Zhang, Cheng
Wen, Qin
Zhang, Xi
BONE MARROW TRANSPLANTATION, 2024, 59 : 176 - 177
[34] PEVONEDISTAT (P), VENETOCLAX (V) AND AZACITIDINE (A) VERSUS V plus A IN ADULT PATIENTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA WHO ARE UNSUITABLE FOR INTENSIVE CHEMOTHERAPY: A RANDOMIZED, PHASE 2 TRIAL (NCT04266795)
Papayannidis, C.
Sedarati, F.
Zhao, D.
Tsukurov, O.
Friedlander, S.
Faller, D. V.
Short, N. J.
HAEMATOLOGICA, 2021, 106 (10) : 50 - 51
[35] Higher-dose venetoclax with measurable residual disease-guided azacitidine discontinuation in newly diagnosed acute myeloid leukemia
Gutman, Jonathan A.
Winters, Amanda
Kent, Andrew
Amaya, Maria
Mcmahon, Christine
Smith, Clayton
Jordan, Craig T.
Stevens, Brett
Minhajuddin, Mohammad
Pei, Shanshan
Schowinsky, Jeffrey
Tobin, Jennifer
O'Brien, Kelly
Falco, Angela
Taylor, Elizabeth
Brecl, Constance
Zhou, Katie
Ho, Phuong
Sohalski, Connor
Dell-Martin, Jessica
Ondracek, Olivia
Abbott, Diana
Pollyea, Daniel A.
HAEMATOLOGICA, 2023, 108 (10) : 2616 - 2625
[36] A prospective study of all-trans retinoic acid plus venetoclax and azacitidine in newly diagnosed acute myeloid leukemia.
Gu, Chengyuan
Wang, Ruju
Kang, Huizhu
He, Xuefeng
Chen, Jun
Lin, Zhihong
Liu, Yuejun
Yang, Ting
Wu, Depei
Han, Yue
JOURNAL OF CLINICAL ONCOLOGY, 2024, 42 (16)
[37] A Phase I Study of Pevonedistat, Azacitidine and Venetoclax for Patients with Relapsed/Refractory Acute Myelogenous Leukemia (AML)
Murthy, Guru Subramanian Guru
Kaufmann, Scott H.
Szabo, Aniko
Harrington, Alexandra M.
Michaelis, Laura C.
Abedin, Sameem
Carlson, Karen
Runaas, Lyndsey
Longo, Walter L.
Hinman, Alexander
Maldonado-Schmidt, Sonia
Thomas, Althea
Baim, Arielle
Litzow, Mark R.
Atallah, Ehab L.
BLOOD, 2021, 138
[38] Venetoclax-based combinations for the treatment of newly diagnosed acute myeloid leukemia
Othman, Tamer A.
Azenkot, Tali
Moskoff, Benjamin N.
Tenold, Matthew E.
Jonas, Brian A.
FUTURE ONCOLOGY, 2021, 17 (23) : 2989 - 3005
[39] Outcomes in patients with newly diagnosed TP53-mutated acute myeloid leukemia with or without venetoclax-based therapy
Venugopal, Sangeetha
Shoukier, Mahran
Konopleva, Marina
Dinardo, Courtney D.
Ravandi, Farhad
Short, Nicholas J.
Andreeff, Michael
Borthakur, Gautam
Daver, Naval
Pemmaraju, Naveen
Sasaki, Koji
Montalban-Bravo, Guillermo
Marx, Kayleigh R.
Pierce, Sherry
Popat, Uday R.
Shpall, Elizabeth J.
Kanagal-Shamanna, Rashmi
Garcia-Manero, Guillermo
Kantarjian, Hagop M.
Kadia, Tapan M.
CANCER, 2021, 127 (19) : 3541 - 3551
[40] Azacitidine in combination with shortened venetoclax treatment cycles in patients with acute myeloid leukemia
Fleischmann, Maximilian
Jentzsch, Madlen
Brioli, Annamaria
Eisele, Florian
Frietsch, Jochen J.
Eigendorff, Farina
Tober, Romy
Schrenk, Karin G.
Hammersen, Jakob Friedrich
Yomade, Olaposi
Hilgendorf, Inken
Hochhaus, Andreas
Scholl, Sebastian
Schnetzke, Ulf
ANNALS OF HEMATOLOGY, 2025, 104 (01) : 285 - 294

← 1 2 3 4 5 →