Trabal Adriana, Gibson Amber, He Jiasen, McCall David, Roth Michael, Nuñez Cesar, Garcia Miriam, Buzbee Meredith, Toepfer Laurie, Bidikian Aram, Daver Naval, Kadia Tapan, Short Nicholas J, Issa Ghayas C, Ravandi Farhad, DiNardo Courtney D, Montalban Bravo Guillermo, Garces Sofia, Marcogliese Andrea, Paek Hana, Dreyer Zoann, Brackett Julienne, Redell Michele, Yi Joanna, Garcia-Manero Guillermo, Konopleva Marina, Stevens Alexandra, Cuglievan Branko
Department of Pediatric Hematology/Oncology, Golisano Children's Hospital, Fort Myers, FL 33908, USA.
Department of Pediatric Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Cancers (Basel). 2023 Mar 26;15(7):1983. doi: 10.3390/cancers15071983.
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 (n = 17), WT1 (n = 13), FLT3-ITD (n = 10), monosomy 7 (n = 5), TP53 (n = 3), Inv(3) (n = 3), (n = 2), monosomy 5 (n = 1), (n = 1) and (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.
BCL-2抑制剂维奈克拉与低强度治疗联合使用可提高成年急性髓系白血病（AML）患者的生存率，但其对儿童AML患者的益处仍不明确。我们回顾性分析了德克萨斯医学中心两家机构对43例儿童AML患者使用维奈克拉的经验；中位年龄17岁（范围0.6 - 21岁）。该人群具有高度难治性；44%的患者（n = 19）接受过≥3线既往治疗，37%（n = 16）接受过既往骨髓移植，81%（n = 35）具有不良遗传学特征（n = 17）、WT1（n = 13）、FLT3-ITD（n = 10）、单体7（n = 5）、TP53（n = 3）、Inv(3)（n = 3）、（n = 2）、单体5（n = 1）、（n = 1）和（n = 1）。大多数患者（86%）接受维奈克拉联合去甲基化药物治疗。3级或4级不良事件包括37%（n = 16）的患者发生发热性中性粒细胞减少、12%（n = 5）的患者发生非发热性中性粒细胞减少、14%（n = 6）的患者发生贫血、14%（n = 6）的患者发生血小板减少。在40例可评估缓解情况的患者中，10例患者（25%）达到完全缓解（CR），6例患者（15%）达到血细胞计数未完全恢复的完全缓解（CRi），2例患者（5%）获得部分缓解，（CR/CRi综合缓解率 = 40%；总缓解率 = 45%）。11例（25%）患者在维奈克拉联合治疗后接受了造血干细胞移植，6例患者仍存活（中位随访时间33.6个月）。中位无事件生存期和总生存期分别为3.7个月和8.7个月。我们的研究结果表明，在儿童AML患者中，维奈克拉耐受性良好，安全性与成人相似。需要更多研究来为儿童人群确定基于维奈克拉的最佳治疗方案。
