Standardized monitoring and testing to help precise treatment, the series of lectures on standardized diagnosis, treatment and management of chronic myeloid leukemia has set sail again

On July 6 and 30, 2022, "Chronic Myeloid Leukemia (CML) Standardized Diagnosis and Management Series Tour Lectures" were held in the "Cloud" successively

"CML Standardized Diagnosis and Treatment Tour" invited Prof.

Following the launch of the CML standardized diagnosis and treatment system, the "CML Standardized Diagnosis and Treatment Tour" set sail again.

Professor Wang Jianxiang

• Hematology Hospital, Institute of Hematology, Chinese Academy of Medical Sciences

• Director of National Hematology Clinical Research Center

• Former Chairman of the Chinese Medical Association Hematology Branch

• Vice President of Internal Medicine Branch of Chinese Medical Doctor Association

• Vice President of Hematology Branch of Chinese Medical Doctor Association

• J Hematol & Oncol Associate Editor

• Blood Editorial Board

• Editor-in-Chief of Chinese Journal of Hematology (2012-2016)

• Chairman of the Hematology and Oncology Committee of China Anti-Cancer Association (2012-2015)

• "Outstanding Youth", "New Century Hundreds and Tens of Thousands of Talents Project" National Candidates, Tribute Experts of the Ministry of Health, Special Post Experts of the State Council

• The main developer of CD19, CD33 CAR-T

• A leader in leukemia treatment, prognostic stratification, intensive induction, and full management have significantly improved the efficacy of acute leukemia

  
  

• Led the formulation of several guidelines for the diagnosis and treatment of "Acute Myeloid Leukemia", "Acute Lymphoblastic Leukemia" and "Chronic Myeloid Leukemia"

• NIH Postdoctoral Outstanding Research Award, the first prize of the 10th "Wu Jieping Medical Research Award - Paul Janssen Pharmaceutical Research Award", the first prize of Tianjin Science and Technology Progress Award (the first person to complete it)

Professor Yang Haiping

• Leader of Hematology Department of the First Affiliated Hospital of Henan University of Science and Technology

• Director of Hematology Department, Chief Physician, Doctor of Medicine, Master Supervisor

• Chairman of Hematology Professional Society of Luoyang Medical Association

• Vice Chairman of Henan Society of Hematology and Immunology

• Vice Chairman of Luoyang Experimental Hematology Society

• Standing Committee Member of Henan Society of Hematology

• Member of Hematology Society of Henan Medical Association

• Good at diagnosis and treatment of various difficult anemia, bleeding, jaundice and fever

• Good at chemotherapy of hematological malignancies such as leukemia, lymphoma, and multiple myeloma

• He is good at hematopoietic stem cell transplantation and has accumulated rich experience in the management of transplant complications

• Published 6 SCI papers, 20 Chinese papers, edited 2 books, 3 scientific researches, 3 patents, presided over 3 scientific research projects, and 5 clinical studies

The chairman of the conference, Professor Wang Jianxiang, and the executive chairman, Professor Yang Haiping, said that the emergence of tyrosine kinase inhibitors (TKIs) has greatly prolonged the survival of CML patients, and their management cycle has been significantly longer

Under the auspices of Professor Tian Hongqi from Luoyang Central Hospital Affiliated to Zhengzhou University, Professor Liu Bingcheng first introduced the CML standardized diagnosis and treatment project process, and then comprehensively interpreted the latest CML guidelines from the aspects of diagnosis, staging, and treatment

She pointed out that the latest guidelines for CML emphasize that with typical clinical manifestations, CML can be diagnosed with a combination of Ph chromosome or BCR-ABL1 fusion gene

discussion session

Prof.
Zhang Haiyan of Linyi People's Hospital, Prof.
Chai Tie of Tangshan Workers' Hospital and Prof.
Zhang Haixia of North China University of Science and Technology Affiliated Hospital had wonderful discussions
.

The main contents are as follows:

1.
If a patient with T315I mutation is detected, can a third-generation TKI drug be directly selected?

If T315I mutation is found during first-line treatment, third-generation TKI drugs can be directly selected, but the proportion of early clones in newly diagnosed patients may be very small.
Even if there is T315I mutation, detection methods with low sensitivity may not be able to identify, and clinical attention should be continued
.

 

2.
Can elderly patients stop taking the drug?

Research presented at the 2021 ASH meeting showed that atypical patients had similar discontinuation success rates to classic discontinuation success, while a higher proportion of patients experienced disease progression after relapse
.

Elderly patients should be cautiously discontinued, and dose optimization can be performed, but regular monitoring is required, with timely follow-up and treatment response assessment every three months
.

Significance of CML Standardized Monitoring and Detection

Under the auspices of Professor Tian Hongqi from the Luoyang Central Hospital Affiliated to Zhengzhou University, Professor Hua Luoming gave an academic lecture entitled "The Significance of Standardized Monitoring and Detection of CML"
.

Standardized monitoring and detection is the key to chronic CML management
.

Molecular surveillance was associated with TKI treatment, and patients with less frequent molecular surveillance had lower disease progression, risk of death, emergency room visits and hospitalizations, and lower healthcare costs
.

Standardized monitoring of BCR-ABL fusion gene expression level is an important prerequisite for follow-up efficacy evaluation and guidance of medication
.

Domestic and foreign guidelines point out that BCR-ABL fusion gene monitoring at 3, 6, and 12 months is a milestone in the treatment of CML
.

Standardized monitoring of BCR-ABL levels can identify patients in the "warning" or "failure" phase as early as possible and detect drug resistance
.

Both domestic and foreign guidelines recommend that patients in the "warning" or "failure" stage undergo BCR-ABL kinase domain mutation testing
.

If the timing of mutation detection is too late, 2/3 of CML patients will have poor survival, and early detection and early adjustment of the plan are more conducive to long-term benefits for patients
.

Performing routine mutational analysis of the BCR-ABL kinase domain can guide subsequent therapy
.

T315I is the most common mutation type in TKI-resistant patients, and first- and second-generation TKIs are not effective for T315I-mutated patients.
Therefore, blindly changing drugs without mutation detection cannot meet the treatment needs and delay the treatment time.
, wasting treatment costs
.

Improving the awareness and quality of mutation detection can achieve precise treatment of point mutations, which is an important part of drug selection and efficacy evaluation for CML patients.
Precision treatment can bring more precise long-term survival benefits to patients
.

"Drug therapy" + "regular PCR standardized monitoring" + "standardized mutation detection" will become the ultimate weapon to help CML patients move towards a cure
.

discussion session

Prof.
Gao Feng from the Affiliated Hospital of North China University of Technology, Prof.
Jie Guitao from Linyi Central Hospital, and Prof.
You Yueming from Hebei PetroChina Central Hospital had wonderful discussions
.

The main contents are as follows:

1.
With the first/second generation TKI drugs targeting BCR-ABL until the third generation TKI is launched in China, the treatment of CML has made revolutionary progress
.

With the continuous emergence of new precise targeted therapy drugs and the continuous improvement of precise detection methods, CML has transformed from an incurable malignant hematological tumor to a "chronic disease" that currently achieves functional cure
.

In the long-term chronic disease management process, the standardized management of CML, especially the standardized management of CML in primary hospitals, is very important
.

2.
Standardized monitoring is of great significance to the treatment of CML.
For example, young high-risk patients are monitored for changes in their condition during the treatment of a generation of TKI drugs, and the drugs can be changed in time, which can achieve good curative effects, especially for patients with T315I mutation.
Ni treatment works very well
.

3.
CML patients can combine different treatment goals.
For example, the treatment goal of elderly patients is survival time (OS), and the treatment goal of some young and even middle-aged and elderly patients is treatment-free remission (TFR).
Appropriately select first-, second-, and third-generation TKIs.
Medications to achieve the corresponding depth of relief
.

project discussion

Under the auspices of Prof.
Liu Bingcheng, Prof.
Hua Luoming and Prof.
Yang Haiping, the 16 panelists at the meeting focused on the diagnosis and staging of CML, treatment and efficacy evaluation of CML, regular follow-up and standardized monitoring, mutation detection and precise treatment, Standardized diagnosis and treatment of drug-resistant CML patients, sharing and discussion of difficult cases, etc.
, launched a multi-dimensional academic discussion on standardized diagnosis and treatment of CML
.

The main contents are as follows:

1.
An elderly patient goes to the doctor because of elevated platelets, and the Ph chromosome and BCR-ABL1 fusion gene are positive.
FISH is not performed.
How should it be diagnosed and whether monitoring is required?

BCR-ABL—CML“”，PhBCR-ABL1CML
。
（FISH）JAK2、MPL、CALR，
。
JAK2、MPL、CALR，BCR-ABL，JAK2，BCR-ABLJAK2
。

2.
（BP）/TKI，？

TKIBP，，
。
，TKI
。
，，
。

3.
TKIT315I，TKI？

T315I/TKI，
。
CP，MMR，，，3-4
。

4.
TKI，TKITKI？

For patients who failed the second-generation therapy due to poor efficacy, the later the number of treatment lines, the higher the failure rate.
Less than third-generation TKI drugs
.

The ELN guidelines also recommend direct switching to third-generation drugs after failure of second-generation TKI therapy
.

5.
Young BP patients with non-T315I mutation have good curative effect after switching to orebatinib.
How long should TKI continue to be maintained after transplantation?

In addition to close monitoring of MRD after transplantation, these patients also require maintenance therapy with TKI drugs
.

Studies have shown that if the leukemia does not relapse for 5 years, the clinical cure rate is more than 80%
.

The longer the duration of maintenance treatment, the less likely to relapse, and should be maintained for at least five years
.

6.
When the patient reaches the withdrawal standard, should the dose be gradually reduced or should be discontinued directly?

Whether or not the drug is discontinued depends mainly on the patient's wishes
.

If the patient does not pursue discontinuation, the dose can be gradually reduced to the lowest safe dose
.

If the patient has a strong willingness to stop the drug, the success rate of reducing the dose first and then stopping the drug is 20-30% higher than that of direct drug withdrawal
.

Regarding the problem of recurrence after drug withdrawal, 99% of patients with recurrence after drug withdrawal are molecular recurrence, which can be recovered by re-medication
.

Summary of the meeting

At the end of the meeting, Professor Wang Jianxiang concluded that in recent years, CML treatment drugs have continued to develop, but there are still problems such as drug intolerance, poor efficacy, and disease progression during the treatment process
.

In order to achieve better treatment effects, it is necessary to continuously update treatment and monitoring methods, and adjust treatment plans according to the results of monitoring
.

The "CML Standardized Diagnosis and Treatment Tour" conducted in-depth discussions on CML diagnosis and treatment and monitoring.
The participating experts not only gained insights, but also developed ideas.
It is hoped that through the exchanges and learning in the conference, the most advanced standardized management concept of CML can be passed on to more people clinicians, thereby benefiting more patients with CML
.

Edit: May Typesetting: moly Execution: siqili

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