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

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

Chengtao Zhang  1 , Da Gao  2 , Xiaohong Wang  3 , Xiuli Sun  4 , Yan Yan  5 , Yan Yang  1 , Jingjing Zhang  1 , Jinsong Yan  1   6   7
Affiliations

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

Chengtao Zhang et al. Front Oncol. .

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/m2/day on days 1 and 4; homoharringtonine, 4 mg/m2/day for 5 days, and cytarabine, 1.5 g/m2/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% (P=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 >0.5×109/L and time to platelet count >20×109/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.

Keywords: FLT3 mutation; acute myeloid leukemia; bortezomib; homoharringtonine; induction; refractory and relapsed.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The 1-year estimated overall survival in all patients (A) and relapse-free survival in patients who had achieved CR/CRi (B). (A) The 1-year estimated OS rate was 27.8% in all patients. (B) Among 8 patients who had achieved CR/CRi, the 1-year estimated RFS rate was 50%.
Figure 2
Figure 2
1-year estimated OS in transplantation patients (A) and in patients with FLT3 mutation (B). (A) 1-year estimated OS rate was 44.4% in 9 patients who received transplantation, the median OS was not reached to investigation point in non-transplanted patients (P=0.03). (B) 1-year estimated OS rates was 44.4% in 9 FLT3-mutation patients, while 16.7% in 12 non-FLT3 mutation patients (P=0.12).
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