Effectiveness of chemotherapy using bortezomib combined with homoharringtonine and cytarabine in refractory or relapsed acute myeloid leukemia: a phase II, multicenter, prospective clinical trial
BackgroundRefractory/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.ObjectivesTo investigate CR/CR with incomplete...
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| Format: | Article |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1142449/full |
| _version_ | 1797741125562269696 |
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| author | Chengtao Zhang Da Gao Xiaohong Wang Xiuli Sun Yan Yan Yan Yang Jingjing Zhang Jinsong Yan Jinsong Yan Jinsong Yan |
| author_facet | Chengtao Zhang Da Gao Xiaohong Wang Xiuli Sun Yan Yan Yan Yang Jingjing Zhang Jinsong Yan Jinsong Yan Jinsong Yan |
| author_sort | Chengtao Zhang |
| collection | DOAJ |
| description | BackgroundRefractory/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.ObjectivesTo 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.MethodsWe 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.ResultsAfter 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.ConclusionBHA 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 registrationhttps://www.chictr.org.cn/, identifier ChiCTR2000029841. |
| first_indexed | 2024-03-12T14:22:22Z |
| format | Article |
| id | doaj.art-66e9760abfd245eaa77c72dcd62e58a5 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-12T14:22:22Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-66e9760abfd245eaa77c72dcd62e58a52023-08-18T14:29:52ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-08-011310.3389/fonc.2023.11424491142449Effectiveness of chemotherapy using bortezomib combined with homoharringtonine and cytarabine in refractory or relapsed acute myeloid leukemia: a phase II, multicenter, prospective clinical trialChengtao Zhang0Da Gao1Xiaohong Wang2Xiuli Sun3Yan Yan4Yan Yang5Jingjing Zhang6Jinsong Yan7Jinsong Yan8Jinsong Yan9Department 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, ChinaDepartment of Hematology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, ChinaDepartment of Hematology, The ChaoYang Central Hospital, Liaoning, ChinaDepartment of Hematology, The First Affiliated Hospital of Dalian Medical University, Dalian, ChinaDepartment of Hematology, Bayannur Hospital, Bayannur, Inner Mongolia, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaBlood Stem Cell Transplantation Institute of Dalian Medical University, Dalian, ChinaPediatric Oncology and Hematology Center of the Second Hospital of Dalian Medical University, Dalian, ChinaBackgroundRefractory/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.ObjectivesTo 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.MethodsWe 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.ResultsAfter 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.ConclusionBHA 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 registrationhttps://www.chictr.org.cn/, identifier ChiCTR2000029841.https://www.frontiersin.org/articles/10.3389/fonc.2023.1142449/fullacute myeloid leukemiarefractory and relapsedbortezomibhomoharringtonineFLT3 mutationinduction |
| spellingShingle | Chengtao Zhang Da Gao Xiaohong Wang Xiuli Sun Yan Yan Yan Yang Jingjing Zhang Jinsong Yan Jinsong Yan Jinsong Yan Effectiveness of chemotherapy using bortezomib combined with homoharringtonine and cytarabine in refractory or relapsed acute myeloid leukemia: a phase II, multicenter, prospective clinical trial Frontiers in Oncology acute myeloid leukemia refractory and relapsed bortezomib homoharringtonine FLT3 mutation induction |
| title | Effectiveness of chemotherapy using bortezomib combined with homoharringtonine and cytarabine in refractory or relapsed acute myeloid leukemia: a phase II, multicenter, prospective clinical trial |
| title_full | Effectiveness of chemotherapy using bortezomib combined with homoharringtonine and cytarabine in refractory or relapsed acute myeloid leukemia: a phase II, multicenter, prospective clinical trial |
| title_fullStr | Effectiveness of chemotherapy using bortezomib combined with homoharringtonine and cytarabine in refractory or relapsed acute myeloid leukemia: a phase II, multicenter, prospective clinical trial |
| title_full_unstemmed | Effectiveness of chemotherapy using bortezomib combined with homoharringtonine and cytarabine in refractory or relapsed acute myeloid leukemia: a phase II, multicenter, prospective clinical trial |
| title_short | Effectiveness of chemotherapy using bortezomib combined with homoharringtonine and cytarabine in refractory or relapsed acute myeloid leukemia: a phase II, multicenter, prospective clinical trial |
| title_sort | effectiveness of chemotherapy using bortezomib combined with homoharringtonine and cytarabine in refractory or relapsed acute myeloid leukemia a phase ii multicenter prospective clinical trial |
| topic | acute myeloid leukemia refractory and relapsed bortezomib homoharringtonine FLT3 mutation induction |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1142449/full |
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