Venetoclax for Acute Myeloid Leukemia in Pediatric Patients: A Texas Medical Center Experience

被引：26

作者：

Trabal, Adriana ^{[1
]}

Gibson, Amber ^{[2
]}

He, Jiasen ^{[2
]}

McCall, David ^{[2
]}

Roth, Michael ^{[2
]}

Nunez, Cesar ^{[2
]}

Garcia, Miriam ^{[2
]}

Buzbee, Meredith ^{[2
]}

Toepfer, Laurie ^{[2
]}

Bidikian, Aram ^{[3
]}

Daver, Naval ^{[3
]}

Kadia, Tapan ^{[3
]}

Short, Nicholas J. ^{[3
]}

Issa, Ghayas C. ^{[3
]}

Ravandi, Farhad ^{[3
]}

DiNardo, Courtney D. ^{[3
]}

Bravo, Guillermo Montalban ^{[3
]}

Garces, Sofia ^{[4
]}

Marcogliese, Andrea ^{[5
]}

Paek, Hana ^{[6
]}

Dreyer, Zoann ^{[6
]}

Brackett, Julienne ^{[6
]}

Redell, Michele ^{[6
]}

Yi, Joanna ^{[6
]}

Garcia-Manero, Guillermo ^{[3
]}

Konopleva, Marina ^{[7
]}

Stevens, Alexandra ^{[6
]}

Cuglievan, Branko ^{[2
]}

机构：

[1] Golisano Childrens Hosp, Dept Pediat Hematol Oncol, Ft Myers, FL 33908 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Pediat Oncol, Houston, TX 77030 USA

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

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

[5] Texas Childrens Hosp, Dept Pathol & Immunol, Houston, TX 77030 USA

[6] Texas Childrens Hosp, Baylor Coll Med, Dept Pediat, Sect Hematol Oncol, Houston, TX 77030 USA

[7] Albert Einstein Coll Med, Dept Oncol, Bronx, NY 10461 USA

来源：

CANCERS | 2023年 / 15卷 / 07期

基金：

美国国家卫生研究院;

关键词：

acute myeloid leukemia; pediatric; children; venetoclax; Bcl-2; inhibitor; CHILDREN; COMBINATION; INHIBITOR; DISEASE; TRIAL;

D O I：

10.3390/cancers15071983

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Simple Summary: Pediatric patients with relapsed or refractory acute myeloid leukemia (AML) have poor survival with current therapy. Venetoclax is a small molecule inhibitor that has shown promise in both adult and pediatric leukemias. Here we describe the joint experience of the Texas Medical Center (The University of Texas MD Anderson Cancer Center and Baylor College of Medicine/Texas Children's Hospital) use of venetoclax in combination with various therapies for the treatment of pediatric relapsed AML. We report the safety and efficacy of this regimen in this population. The BCL-2 inhibitor venetoclax improves survival for adult patients with acute myeloid leukemia (AML) in combination with lower-intensity therapies, but its benefit in pediatric patients with AML remains unclear. We retrospectively reviewed two Texas Medical Center institutions' experience with venetoclax in 43 pediatric patients with AML; median age 17 years (range, 0.6-21). This population was highly refractory; 44% of patients (n = 19) had >= 3 prior lines of therapy, 37% (n = 16) had received a prior bone marrow transplant, and 81% (n = 35) had unfavorable genetics KMT2A (n = 17), WT1 (n = 13), FLT3-ITD (n = 10), monosomy 7 (n = 5), TP53 (n = 3), Inv(3) (n = 3), IDH1/2 (n = 2), monosomy 5 (n = 1), NUP98 (n = 1) and ASXL1 (n = 1). The majority (86%) received venetoclax with a hypomethylating agent. Grade 3 or 4 adverse events included febrile neutropenia in 37% (n = 16), non-febrile neutropenia in 12% (n = 5), anemia in 14% (n = 6), and thrombocytopenia in 14% (n = 6). Of 40 patients evaluable for response, 10 patients (25%) achieved complete response (CR), 6 patients (15%) achieved CR with incomplete blood count recovery (CRi), and 2 patients (5%) had a partial response, (CR/CRi composite = 40%; ORR = 45%). Eleven (25%) patients received a hematopoietic stem cell transplant following venetoclax combination therapy, and six remain alive (median follow-up time 33.6 months). Median event-free survival and overall survival duration was 3.7 months and 8.7 months, respectively. Our findings suggest that in pediatric patients with AML, venetoclax is well-tolerated, with a safety profile similar to that in adults. More studies are needed to establish an optimal venetoclax-based regimen for the pediatric population.

引用

页数：15

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