Venetoclax and hypomethylating agent combination therapy in newly diagnosed acute myeloid leukemia: Genotype signatures for response and survival among 301 consecutive patients

被引：41

作者：

Gangat, Naseema ^{[1
,4
]}

Karrar, Omer ^{[1
]}

Iftikhar, Moazah ^{[1
]}

Mccullough, Kristen ^{[1
]}

Johnson, Isla M. ^{[1
]}

Abdelmagid, Maymona ^{[1
]}

Abdallah, Mostafa ^{[1
]}

Al-Kali, Aref ^{[1
]}

Alkhateeb, Hassan B. ^{[1
]}

Begna, Kebede H. ^{[1
]}

Mangaonkar, Abhishek ^{[1
]}

Saliba, Antoine N. ^{[1
]}

Torghabeh, Mehrdad Hefazi ^{[1
]}

Litzow, Mark R. ^{[1
]}

Hogan, William ^{[1
]}

Shah, Mithun ^{[1
]}

Patnaik, Mrinal M. ^{[1
]}

Pardanani, Animesh ^{[1
]}

Badar, Talha ^{[2
]}

Murthy, Hemant ^{[2
]}

Foran, James ^{[2
]}

Palmer, Jeanne ^{[3
]}

Sproat, Lisa ^{[3
]}

Khera, Nandita ^{[3
]}

Yi, Cecilia Arana ^{[3
]}

Tefferi, Ayalew ^{[1
]}

机构：

[1] Mayo Clin, Div Hematopathol, Rochester, MN USA

[2] Div Hematol, Mayo Clin, Jacksonville, FL USA

[3] Mayo Clin, Div Hematol, Scottsdale, AZ USA

[4] Mayo Clin, Dept Med, Div Hematol, 200 First St SW, Rochester, MN 55905 USA

来源：

AMERICAN JOURNAL OF HEMATOLOGY | 2024年 / 99卷 / 02期

关键词：

MEASURABLE RESIDUAL DISEASE; AZACITIDINE;

D O I：

10.1002/ajh.27138

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Venetoclax + hypomethylating agent (Ven-HMA) is currently the standard frontline therapy for older/unfit patients with newly diagnosed acute myeloid leukemia (ND-AML). Our objective in the current retrospective study of 301 adult patients (median age 73 years; 62% de novo) with ND-AML was to identify molecular predictors of treatment response to Ven-HMA and survival; European LeukemiaNet (ELN) genetic risk assignment was favorable 15%, intermediate 16%, and adverse 69%. Complete remission, with (CR) or without (CRi), count recovery, was documented in 182 (60%) patients. In multivariable analysis, inclusive of mutations only, "favorable" predictors of CR/CRi were NPM1 (86% vs. 56%), IDH2 (80% vs. 58%), and DDX41 (100% vs. 58%) and "unfavorable" TP53 (40% vs. 67%), FLT3-ITD (36% vs. 63%), and RUNX1 (44% vs. 64%) mutations; significance was sustained for each mutation after adjustment for age, karyotype, and therapy-related qualification. CR/CRi rates ranged from 36%, in the presence of unfavorable and absence of favorable mutation, to 91%, in the presence of favorable and absence of unfavorable mutation. At median follow-up of 8.5 months, 174 deaths and 41 allogeneic stem cell transplants (ASCT) were recorded. In multivariable analysis, risk factors for inferior survival included failure to achieve CR/CRi (HR 3.4, 95% CI 2.5-4.8), adverse karyotype (1.6, 1.1-2.6), TP53 mutation (1.6, 1.0-2.4), and absence of IDH2 mutation (2.2, 1.0-4.7); these risk factors were subsequently applied to construct an HR-weighted risk model that performed better than the ELN genetic risk model (AIC 1661 vs. 1750): low (n = 130; median survival 28.9 months), intermediate (n = 105; median 9.6 months), and high (n = 66; median 3.1 months; p < .001); survival in each risk category was significantly upgraded by ASCT. The current study identifies genotype signatures for predicting response and proposes a 3-tiered, CR/CRi-based, and genetics-enhanced survival model for AML patients receiving upfront therapy with Ven-HMA.

引用

页码：193 / 202

页数：10

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