Effectiveness of Chemotherapy Using Bortezomib Combined with Homoharringtonine and Cytarabine in Refractory or Relapsed Acute Myeloid Leukemia: a Phase II, Multicenter, Prospective Clinical Trial

Overview

Journal Front Oncol

Specialty Oncology

Date 2023 Sep 4

PMID 37664023

Authors

Chengtao Zhang

Da Gao

Xiaohong Wang

Xiuli Sun

Yan Yan

Yan Yang

Jingjing Zhang

Jinsong Yan

Affiliations

Soon will be listed here.

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.

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