Venetoclax combined with FLAG-IDA induction and consolidation in newly diagnosed acute myeloid leukemia

被引：72

作者：

DiNardo, Courtney D. ^{[1
]}

Lachowiez, Curtis A. ^{[2
]}

Takahashi, Koichi ^{[1
]}

Loghavi, Sanam ^{[3
]}

Kadia, Tapan ^{[1
]}

Daver, Naval ^{[1
]}

Xiao, Lianchun ^{[4
]}

Adeoti, Maria ^{[1
]}

Short, Nicholas J. ^{[1
]}

Sasaki, Koji ^{[1
]}

Wang, Sa A. ^{[3
]}

Borthakur, Gautam ^{[1
]}

Issa, Ghayas ^{[1
]}

Maiti, Abhishek ^{[1
]}

Alvarado, Yesid ^{[1
]}

Pemmaraju, Naveen ^{[1
]}

Bravo, Guillermo Montalban ^{[1
]}

Masarova, Lucia ^{[1
]}

Yilmaz, Musa ^{[2
]}

Jain, Nitin ^{[1
]}

Andreeff, Michael ^{[1
]}

Garcia-Manero, Guillermo ^{[1
]}

Kornblau, Steven ^{[1
]}

Ravandi, Farhad ^{[1
]}

Jabbour, Elias ^{[1
]}

Konopleva, Marina Y. ^{[1
]}

Kantarjian, Hagop M. ^{[1
]}

机构：

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

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

[3] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA

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

来源：

AMERICAN JOURNAL OF HEMATOLOGY | 2022年 / 97卷 / 08期

关键词：

MINIMAL RESIDUAL DISEASE; HIGH-RISK; CHEMOTHERAPY; CYTARABINE; ADULTS; TRANSPLANTATION; RECOMMENDATIONS; DAUNORUBICIN; MULTICENTER; FLUDARABINE;

D O I：

10.1002/ajh.26601

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Multi-agent induction chemotherapy (IC) improves response rates in younger patients with acute myeloid leukemia (AML); however, relapse remains the principal cause of treatment failure. Improved induction regimens are needed. A prospective single-center phase Ib/II study evaluating fludarabine, cytarabine, G-CSF, and idarubicin combined with venetoclax (FLAG-IDA + VEN) in patients with newly diagnosed (ND) or relapsed/refractory AML. The primary efficacy endpoint was assessment of overall activity (overall response rate [ORR]: complete remission [CR] + CR with partial hematologic recovery [CRh] + CR with incomplete hematologic recovery [CRi] + morphologic leukemia free state + partial response). Secondary objectives included additional assessments of efficacy, overall survival (OS), and event-free survival (EFS). Results of the expanded ND cohort with additional follow-up are reported. Forty-five patients (median age: 44 years [range 20-65]) enrolled. ORR was 98% (N = 44/45; 95% credible interval 89.9%-99.7%). Eighty-nine percent (N = 40/45) of patients attained a composite CR (CRc + CRh + CRi) including 93% (N = 37/40) who were measurable residual disease (MRD) negative. Twenty-seven (60%) patients transitioned to allogeneic stem cell transplant (alloHSCT). Common non-hematologic adverse events included febrile neutropenia (44%; N = 20), pneumonia (22%, N = 10), bacteremia (18%, N = 8), and skin/soft tissue infections (44%, N = 20). After a median follow-up of 20 months, median EFS and OS were not reached. Estimated 24-month EFS and OS were 64% and 76%, respectively. FLAG-IDA + VEN is an active regimen in ND-AML capable of producing high MRD-negative remission rates and enabling transition to alloHSCT when appropriate in most patients. Toxicities were as expected with IC and were manageable. Estimated 24-month survival appears favorable compared to historical IC benchmarks.

引用

页码：1035 / 1043

页数：9

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