硼替佐米联合高三尖杉酯碱及阿糖胞苷化疗方案治疗难治性或复发性急性髓系白血病的疗效：一项多中心前瞻性II期临床试验

Effectiveness of chemotherapy using bortezomib combined with homoharringtonine and cytarabine in refractory or relapsed acute myeloid leukemia: a phase II, multicenter, prospective clinical trial.

作者信息

Zhang Chengtao, Gao Da, Wang Xiaohong, Sun Xiuli, Yan Yan, Yang Yan, Zhang Jingjing, Yan Jinsong

机构信息

Department of Hematology, Liaoning Key Laboratory of Hematopoietic Stem Cell Transplantation and Translational Medicine, Liaoning Medical Center for Hematopoietic Stem Cell Transplantation, The Second Hospital of Dalian Medical University, Dalian, China.

Department of Hematology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.

出版信息

Front Oncol. 2023 Aug 18;13:1142449. doi: 10.3389/fonc.2023.1142449. eCollection 2023.

DOI:10.3389/fonc.2023.1142449

PMID:37664023

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10472935/

Abstract

BACKGROUND

Refractory/relapsed acute myeloid leukemia (R/R AML) has unsatisfactory outcomes even after allogeneic hematopoietic stem cell transplantation. Long-term survival is mainly influenced by complete remission (CR) rates after induction therapies.

OBJECTIVES

To investigate CR/CR with incomplete hematologic recovery (CRi) rates and adverse events with a new induction therapy (bortezomib, homoharringtonine, and cytarabine [BHA]) for patients with R/R AML.

METHODS

We enrolled 21 patients with R/R AML (median age, 42 [range, 30-62] years), who received BHA for remission induction (bortezomib, 1.3 mg/m/day on days 1 and 4; homoharringtonine, 4 mg/m/day for 5 days, and cytarabine, 1.5 g/m/day for 5 days). CR and adverse events were assessed.

RESULTS

After one course of BHA, the CR/CRi and partial remission rates were 38.1% and 14.3%, respectively, with an overall response rate (ORR) of 52.4% in 21 patients. 9 of 21 patients harbored FLT3-ITD or FLT3-TKD mutations, and achieved either CR/CRi or ORR of 66.7% (=0.03) by comparison with that in R/R AML without FLT3 mutation. After induction therapy, consolidation chemotherapy or allogeneic hematopoietic stem cell transplantation led to a one-year overall survival of 27.8% in all patients. One-year relapse-free survival was 50% in 8 patients who had achieved CR/CRi after one course of BHA. During induction, non-hematologic adverse events (grade 3/4) commonly were infection (90.5%), hypokalemia (14.4%), hypocalcemia (14.3%), and mucositis (9.5%). In patients achieving CR, the median time to neutrophil count >0.5×10/L and time to platelet count >20×10/L were 15 (13-17) days and 13 (13-18) days, respectively.

CONCLUSION

BHA chemotherapy regimen was safe and tolerable to serve as an induction therapy for R/R AML, particularly with FLT3 mutation. The higher CR/CRi rate will give a clue to determine a potentialeffectiveness of BHA for AML patients carrying FLT3 mutation in a further investigation.

CLINICAL TRIAL REGISTRATION

https://www.chictr.org.cn/, identifier ChiCTR2000029841.

摘要

背景

难治性/复发性急性髓系白血病（R/R AML）即使在异基因造血干细胞移植后预后仍不理想。长期生存主要受诱导治疗后的完全缓解（CR）率影响。

目的

研究一种新的诱导治疗方案（硼替佐米、高三尖杉酯碱和阿糖胞苷[BHA]）用于R/R AML患者的CR/伴有血液学不完全恢复的CR（CRi）率及不良事件。

方法

我们纳入了21例R/R AML患者（中位年龄42岁[范围30 - 62岁]），接受BHA进行缓解诱导治疗（硼替佐米，第1天和第4天1.3 mg/m²/天；高三尖杉酯碱，4 mg/m²/天，共5天；阿糖胞苷，1.5 g/m²/天，共5天）。评估CR和不良事件。

结果

经过一个疗程的BHA治疗后，21例患者的CR/CRi率和部分缓解率分别为38.1%和14.3%，总缓解率（ORR）为52.4%。21例患者中有9例携带FLT3 - ITD或FLT3 - TKD突变，与无FLT3突变的R/R AML患者相比，其CR/CRi率或ORR为66.7%（P = 0.03）。诱导治疗后，巩固化疗或异基因造血干细胞移植使所有患者的1年总生存率为27.8%。在经过一个疗程BHA治疗后达到CR/CRi的8例患者中，1年无复发生存率为50%。诱导治疗期间，非血液学不良事件（3/4级）常见的有感染（90.5%）、低钾血症（14.4%）、低钙血症（14.3%）和黏膜炎（9.5%）。在达到CR的患者中，中性粒细胞计数>0.5×10⁹/L的中位时间和血小板计数>20×10⁹/L的中位时间分别为15（13 - 17）天和13（13 - 18）天。