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Acute myeloid leukemia (AML), as one of the common types of leukemia in the blood system, has always been the focus of clinical research
.
In recent years, the diagnosis and treatment of AML and drug research have developed rapidly and have yielded a lot.
In 2021, a number of domestic diagnosis and treatment guidelines will also be updated simultaneously
.
At the beginning of 2022, Yimaitong specially invited Professor Wei Hui from the Hematology Hospital of the Institute of Hematology, Chinese Academy of Medical Sciences to review the research progress of AML in 2021 and discuss the future development direction of AML
.
The treatment of elderly and relapsed/refractory AML patients is still difficult.
The clinical treatment methods for AML mainly include chemotherapy and hematopoietic stem cell transplantation
.
Although adult AML patients can achieve better efficacy after chemotherapy and hematopoietic stem cell transplantation
.
However, for elderly AML patients (≥60 years old) or relapsed and refractory (R/R) AML patients, there is currently a lack of effective treatment methods, which is still a very difficult problem in clinical treatment
.
Although emerging targeted drugs can benefit elderly or R/R AML patients, the prognosis of patients remains unsatisfactory
.
In addition, although chemotherapy and hematopoietic stem cell transplantation are the main treatment methods for AML at present, the treatment-related side effects are relatively large, which affects subsequent treatment.
How to reduce drug toxicity is a content that needs to be further explored in AML research.
Clinically, there is still a need for lower toxicity and lower toxicity.
effective medicine
.
The rapid development of targeted therapy Based on the current status of AML treatment, among the new progress in various research fields of AML, the progress of targeted drugs has attracted much attention
.
Professor Wei Hui summarized the latest progress of AML-related 3 types of targeted drugs (IDH inhibitors, BCL-2 inhibitors, FLT3 inhibitors)
.
The most significant progress is the combination of isocitrate dehydrogenase 1 (IDH1) inhibitors and azacitidine
.
A randomized controlled study found that patients treated with an IDH1 inhibitor in combination with azacitidine achieved higher response rates, longer overall survival, and improved overall survival compared to patients with IDH1 mutations who were treated with azacitidine monotherapy.
long event-free survival
.
This new development also brings new options for elderly IDH1-mutant AML patients who are not suitable for intensive chemotherapy (unfit)
.
Professor Wei Hui believes that this program may rewrite domestic and foreign guidelines in the future
.
Other inhibitors have also made good progress
.
One is the BCL-2 inhibitor veneclax
.
In the past clinical use, veneclax was mostly used in combination with chemotherapy drugs such as azacitidine.
The current study uses veneclax in combination with a series of targeted drugs, including FLT3 inhibitors, unmarketed CD47 monoclonal antibodies, etc.
Or further combined with other drugs on this basis
.
The results of several studies have suggested that the combination of targeted drugs and targeted drugs in the treatment of AML patients can further improve the efficacy compared with the combination of targeted drugs and other treatment options
.
Another drug is FMS-like tyrosine kinase 3 (FLT3) inhibitor, the current main research direction is in combination with azacitidine, "3+7" regimen, etc.
, and it is also trying to be used in the maintenance treatment of AML patients , although no positive results have been obtained so far, the results of these studies are worth looking forward to
.
The study of mutated genes that can guide the treatment of AML patients with targeted drugs is based on the study of AML-related mutated genes
.
Studies have found that the type of AML mutated gene affects the prognosis of the disease
.
For example, common gene mutations in AML include NPM1 mutation, FLT3 mutation, DNMT3A mutation, etc.
These gene mutations are prone to coexist
.
The prognosis of AML patients with NPM1 mutation is good, but the prognosis of AML patients with FLT3 mutation and DNMT3A mutation is poor, and the prognosis of patients with these three gene mutations at the same time is very poor
.
The detection of these mutated genes can help in the selection of clinical treatment drugs and provide individualized treatment for patients
.
Most patients can benefit from it.
For example, patients with NPM1 mutation have better efficacy with veneclax; patients with FLT3-ITD mutation are currently clinically treated with FLT3 inhibitor geritinib and other drugs; CEBPA double mutation is more common in domestic AML patients , such patients can be treated with intensive chemotherapy, and the prognosis is better
.
However, there are also some patients with gene mutations who cannot benefit from it temporarily.
For example, patients with TP53 mutations, the currently marketed targeted drugs, including veneclax, can improve the remission rate, but the long-term efficacy needs to be improved.
In the future, the combination of veneclax Whether CD47 monoclonal antibody can bring better efficacy, more research is needed
.
A number of targeted drugs have been included in the guidelines.
The research on AML-related genes and targeted drugs has progressed rapidly and has yielded fruitful results
.
To this end, in 2021, a number of domestic guidelines have updated the section on innovative targeted drugs, providing new options for AML treatment
.
Here, Prof.
Wei Hui summarized several important drugs that have been updated in domestic guidelines
.
First of all, some elderly patients cannot tolerate intensive chemotherapy due to frailty and comorbidities.
For unfit patients who are newly diagnosed in the elderly, the new guideline adds the BCL-2 inhibitor veneclax
.
The drug is also suitable for adult unfit patients
.
In addition, the new guideline also lists pan-targeted drugs, demethylation drugs, etc.
in the recommended drugs for maintenance treatment of elderly AML patients, and is no longer limited to the "3+7" regimen and hematopoietic stem cell transplantation
.
The new guideline also updates drug recommendations for patients with genetic mutations
.
For AML patients with FLT3-ITD mutation, geritinib can be selected.
For patients with FLT3-ITD mutation after adult allogeneic hematopoietic stem cell transplantation, the guidelines recommend maintenance therapy with FLT3 inhibitors, including sorafenib and gilritinib
.
In addition, IDH inhibitors for the treatment of R/R AML are also reflected in the guidelines, but such drugs have not yet been approved in China, and it is expected that they will be approved and marketed in China in the future
.
In general, the emergence of these innovative targeted drugs and the update of guideline recommendations have the most important significance of improving the efficacy of AML and constantly filling the gaps in clinical treatment
.
Future research directions The importance of targeted drugs in the treatment of AML is obvious to all
.
Targeted drugs are not only a research hotspot in the field of AML, but also a research hotspot in the entire tumor field
.
In addition to targeted therapy, Professor Wei Hui said that immunotherapy is also one of the treatments for AML
.
The use of antibody-based immunotherapy, such as antibody-drug conjugates (ADC), may improve or greatly improve the efficacy of AML, and it is expected to be applied to AML treatment in the future
.
Professor Wei Hui pointed out that disease stratification is also one of the research hotspots in the future
.
Through the study of AML-related mutated genes, the prognostic status of patients can be distinguished according to the mutated genes, and the corresponding drugs can be selected.
For example, FLT3 inhibitors can be used to treat AML patients with FLT3-ITD mutations, and IDH inhibitors can be used to treat patients with IDH mutations
.
In addition, disease stratification can be performed according to minimal residual disease (MRD) after treatment
.
If the patient's MRD remains positive or changes from negative to positive, active hematopoietic stem cell transplantation, targeted therapy or immunotherapy should be considered in clinical practice; if the patient's MRD is negative or declines rapidly, the treatment intensity can be reduced in clinical treatment, with chemotherapy as the Mainly, avoid hematopoietic stem cell transplantation therapy
.
Summary In the past few years, AML research has made continuous new progress, breaking the situation that AML treatment can only rely on chemotherapy and hematopoietic stem cell transplantation
.
In recent years, with the continuous breakthroughs in the exploration of AML-related genes, the emergence of many innovative targeted drugs and innovative therapies has brought good news to AML patients
.
Looking forward to more new progress and breakthroughs in the future, bringing more benefits to AML patients! Professor Wei Hui Chief Physician and Doctoral Supervisor The editor-in-chief graduated from China Medical University in 2000 and obtained a master's degree.
He graduated from China Union Medical College and obtained a doctorate in 2006.
From 2010 to 2013, he worked as a postdoctoral fellow at the National Institutes of Health, mainly engaged in basic and clinical research on leukemia.
", we progress together
.
In recent years, the diagnosis and treatment of AML and drug research have developed rapidly and have yielded a lot.
In 2021, a number of domestic diagnosis and treatment guidelines will also be updated simultaneously
.
At the beginning of 2022, Yimaitong specially invited Professor Wei Hui from the Hematology Hospital of the Institute of Hematology, Chinese Academy of Medical Sciences to review the research progress of AML in 2021 and discuss the future development direction of AML
.
The treatment of elderly and relapsed/refractory AML patients is still difficult.
The clinical treatment methods for AML mainly include chemotherapy and hematopoietic stem cell transplantation
.
Although adult AML patients can achieve better efficacy after chemotherapy and hematopoietic stem cell transplantation
.
However, for elderly AML patients (≥60 years old) or relapsed and refractory (R/R) AML patients, there is currently a lack of effective treatment methods, which is still a very difficult problem in clinical treatment
.
Although emerging targeted drugs can benefit elderly or R/R AML patients, the prognosis of patients remains unsatisfactory
.
In addition, although chemotherapy and hematopoietic stem cell transplantation are the main treatment methods for AML at present, the treatment-related side effects are relatively large, which affects subsequent treatment.
How to reduce drug toxicity is a content that needs to be further explored in AML research.
Clinically, there is still a need for lower toxicity and lower toxicity.
effective medicine
.
The rapid development of targeted therapy Based on the current status of AML treatment, among the new progress in various research fields of AML, the progress of targeted drugs has attracted much attention
.
Professor Wei Hui summarized the latest progress of AML-related 3 types of targeted drugs (IDH inhibitors, BCL-2 inhibitors, FLT3 inhibitors)
.
The most significant progress is the combination of isocitrate dehydrogenase 1 (IDH1) inhibitors and azacitidine
.
A randomized controlled study found that patients treated with an IDH1 inhibitor in combination with azacitidine achieved higher response rates, longer overall survival, and improved overall survival compared to patients with IDH1 mutations who were treated with azacitidine monotherapy.
long event-free survival
.
This new development also brings new options for elderly IDH1-mutant AML patients who are not suitable for intensive chemotherapy (unfit)
.
Professor Wei Hui believes that this program may rewrite domestic and foreign guidelines in the future
.
Other inhibitors have also made good progress
.
One is the BCL-2 inhibitor veneclax
.
In the past clinical use, veneclax was mostly used in combination with chemotherapy drugs such as azacitidine.
The current study uses veneclax in combination with a series of targeted drugs, including FLT3 inhibitors, unmarketed CD47 monoclonal antibodies, etc.
Or further combined with other drugs on this basis
.
The results of several studies have suggested that the combination of targeted drugs and targeted drugs in the treatment of AML patients can further improve the efficacy compared with the combination of targeted drugs and other treatment options
.
Another drug is FMS-like tyrosine kinase 3 (FLT3) inhibitor, the current main research direction is in combination with azacitidine, "3+7" regimen, etc.
, and it is also trying to be used in the maintenance treatment of AML patients , although no positive results have been obtained so far, the results of these studies are worth looking forward to
.
The study of mutated genes that can guide the treatment of AML patients with targeted drugs is based on the study of AML-related mutated genes
.
Studies have found that the type of AML mutated gene affects the prognosis of the disease
.
For example, common gene mutations in AML include NPM1 mutation, FLT3 mutation, DNMT3A mutation, etc.
These gene mutations are prone to coexist
.
The prognosis of AML patients with NPM1 mutation is good, but the prognosis of AML patients with FLT3 mutation and DNMT3A mutation is poor, and the prognosis of patients with these three gene mutations at the same time is very poor
.
The detection of these mutated genes can help in the selection of clinical treatment drugs and provide individualized treatment for patients
.
Most patients can benefit from it.
For example, patients with NPM1 mutation have better efficacy with veneclax; patients with FLT3-ITD mutation are currently clinically treated with FLT3 inhibitor geritinib and other drugs; CEBPA double mutation is more common in domestic AML patients , such patients can be treated with intensive chemotherapy, and the prognosis is better
.
However, there are also some patients with gene mutations who cannot benefit from it temporarily.
For example, patients with TP53 mutations, the currently marketed targeted drugs, including veneclax, can improve the remission rate, but the long-term efficacy needs to be improved.
In the future, the combination of veneclax Whether CD47 monoclonal antibody can bring better efficacy, more research is needed
.
A number of targeted drugs have been included in the guidelines.
The research on AML-related genes and targeted drugs has progressed rapidly and has yielded fruitful results
.
To this end, in 2021, a number of domestic guidelines have updated the section on innovative targeted drugs, providing new options for AML treatment
.
Here, Prof.
Wei Hui summarized several important drugs that have been updated in domestic guidelines
.
First of all, some elderly patients cannot tolerate intensive chemotherapy due to frailty and comorbidities.
For unfit patients who are newly diagnosed in the elderly, the new guideline adds the BCL-2 inhibitor veneclax
.
The drug is also suitable for adult unfit patients
.
In addition, the new guideline also lists pan-targeted drugs, demethylation drugs, etc.
in the recommended drugs for maintenance treatment of elderly AML patients, and is no longer limited to the "3+7" regimen and hematopoietic stem cell transplantation
.
The new guideline also updates drug recommendations for patients with genetic mutations
.
For AML patients with FLT3-ITD mutation, geritinib can be selected.
For patients with FLT3-ITD mutation after adult allogeneic hematopoietic stem cell transplantation, the guidelines recommend maintenance therapy with FLT3 inhibitors, including sorafenib and gilritinib
.
In addition, IDH inhibitors for the treatment of R/R AML are also reflected in the guidelines, but such drugs have not yet been approved in China, and it is expected that they will be approved and marketed in China in the future
.
In general, the emergence of these innovative targeted drugs and the update of guideline recommendations have the most important significance of improving the efficacy of AML and constantly filling the gaps in clinical treatment
.
Future research directions The importance of targeted drugs in the treatment of AML is obvious to all
.
Targeted drugs are not only a research hotspot in the field of AML, but also a research hotspot in the entire tumor field
.
In addition to targeted therapy, Professor Wei Hui said that immunotherapy is also one of the treatments for AML
.
The use of antibody-based immunotherapy, such as antibody-drug conjugates (ADC), may improve or greatly improve the efficacy of AML, and it is expected to be applied to AML treatment in the future
.
Professor Wei Hui pointed out that disease stratification is also one of the research hotspots in the future
.
Through the study of AML-related mutated genes, the prognostic status of patients can be distinguished according to the mutated genes, and the corresponding drugs can be selected.
For example, FLT3 inhibitors can be used to treat AML patients with FLT3-ITD mutations, and IDH inhibitors can be used to treat patients with IDH mutations
.
In addition, disease stratification can be performed according to minimal residual disease (MRD) after treatment
.
If the patient's MRD remains positive or changes from negative to positive, active hematopoietic stem cell transplantation, targeted therapy or immunotherapy should be considered in clinical practice; if the patient's MRD is negative or declines rapidly, the treatment intensity can be reduced in clinical treatment, with chemotherapy as the Mainly, avoid hematopoietic stem cell transplantation therapy
.
Summary In the past few years, AML research has made continuous new progress, breaking the situation that AML treatment can only rely on chemotherapy and hematopoietic stem cell transplantation
.
In recent years, with the continuous breakthroughs in the exploration of AML-related genes, the emergence of many innovative targeted drugs and innovative therapies has brought good news to AML patients
.
Looking forward to more new progress and breakthroughs in the future, bringing more benefits to AML patients! Professor Wei Hui Chief Physician and Doctoral Supervisor The editor-in-chief graduated from China Medical University in 2000 and obtained a master's degree.
He graduated from China Union Medical College and obtained a doctorate in 2006.
From 2010 to 2013, he worked as a postdoctoral fellow at the National Institutes of Health, mainly engaged in basic and clinical research on leukemia.
", we progress together
