Outcomes of older patients with NPM1-mutated AML: current treatments and the promise of venetoclax-based regimens

被引：136

作者：

Lachowiez, Curtis A. ^{[1
]}

Loghavi, Sanam ^{[2
]}

Kadia, Tapan M. ^{[3
]}

Daver, Naval ^{[3
]}

Borthakur, Gautam ^{[3
]}

Pemmaraju, Naveen ^{[3
]}

Naqvi, Kiran ^{[3
]}

Alvarado, Yesid ^{[3
]}

Yilmaz, Musa ^{[3
]}

Short, Nicholas ^{[3
]}

Ohanian, Maro ^{[3
]}

Pierce, Sherry R. ^{[3
]}

Patel, Keyur P. ^{[2
]}

Qiao, Wei ^{[4
]}

Ning, Jing ^{[4
]}

Sasaki, Koji ^{[3
]}

Takahashi, Koichi ^{[3
]}

Jabbour, Elias ^{[3
]}

Andreeff, Michael ^{[3
]}

Ravandi, Farhad ^{[3
]}

Kantarjian, Hagop M. ^{[3
]}

Konopleva, Marina ^{[3
]}

DiNardo, Courtney D. ^{[3
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Div Pathol & Lab Med, Houston, TX 77030 USA

[3] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Div Canc Med, Houston, TX 77030 USA

[4] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA

来源：

BLOOD ADVANCES | 2020年 / 4卷 / 07期

关键词：

ACUTE MYELOID-LEUKEMIA; TRANS-RETINOIC ACID; PROGNOSTIC-SIGNIFICANCE; NPM1; MUTATIONS; NUCLEOPHOSMIN; RELEVANCE; ADULTS; IMPACT; TRIAL;

D O I：

10.1182/bloodadvances.2019001267

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Nucleophosmin-1 mutations (NPM1(+)) occur in similar to 30% of acute myeloid leukemia (AML) patients. Although typically associated with favorable prognosis, the beneficial impact of NPM1(+) decreases with increasing age in patients treated with standard intensive chemotherapy (IC) or hypomethylating agents (HMAs). This retrospective analysis compared outcomes of NPM1(+) AML patients treated with 1 of 3 induction approaches: HMA plus BCL-2 inhibitor venetodax (VEN), HMA, or IC therapy. Composite complete response (CR c : CR + CR with incomplete count recovery) was seen in 96% (27/28), 36% (17/47), and 89% (204/228) of HMA + VEN, HMA, and IC patients, respectively (HMA VEN vs HMA, P < .001; HMA + VEN vs IC, P = .10). Older patients (age >65 years) treated with HMA + VEN, HMA, or IC had CR rates of 88%, 28%, and 56%, respectively (HMA VEN vs HMA, P < .001; HMA + VEN vs IC, P = .01). Significant improvement in overall survival (OS) was seen in patients age >65 years treated with HMA VEN vs HMA (not reached [NR] vs 0.4 years; P < .001) or IC (NR vs 0.93 years; P = .001). Older patients treated with HMA + VEN had OS of 80% after median 1-year follow-up, with estimated 2-year OS of 70%. In the multivariable Cox model analysis, HMA + VEN was associated with a 69% lower risk of death compared with IC (hazard ratio, 0.31; 95% confidence interval, 0.12-0.83; type I error-adjusted P = .038). HMA + VEN combinations demonstrated impressive results compared with traditional standard-of-care regimens in older patients with NPM1(+) AML.

引用

页码：1311 / 1320

页数：10

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