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In order to further promote the communication and development in the field of leukemia and lymphoma diagnosis at home and abroad, "The 6th Anti-leukemia·Lymphoma International Summit Forum and CSCO Anti-Leukemia Alliance & Anti-Lymphoma Alliance Tour Lecture-Harbin Station" in July 2021 Held in Harbin on 8-10
.
This forum brought together many outstanding leukemia and lymphoma experts at home and abroad, and will conduct in-depth discussions and exchanges on new drug development and clinical applications
.
Yimaitong has the honor to invite Professor Xu Bing from the First Affiliated Hospital of Xiamen University and Professor Yang Shenmiao from Peking University People’s Hospital to discuss the new anti-CD20 monoclonal antibody otuzumab in follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL).
) To share the application prospects
.
Yimaitong: First of all, could you please introduce how you give individualized treatment to patients with FL? Professor Xu Bing currently implements stratified treatment for FL according to the stage of the disease.
For patients with stage I or limited stage II FL, nearly 50% of patients can be cured by radiotherapy-based treatment
.
Some patients can be combined with anti-CD20 monoclonal antibody on the basis of radiotherapy to further improve the efficacy and reduce the recurrence rate and disease conversion rate
.
However, the proportion of stage I and limited stage II patients is relatively small, accounting for only 10% of FL
.
Most FL patients are non-limited stage II or III/IV patients.
For this part of FL patients, treatment stratification depends on whether there are indications for treatment
.
For FL patients who are not indicated for treatment, a "watchful and waiting" treatment strategy can be adopted, and treatment can be carried out after the disease has progressed
.
FL patients with indications for treatment are mainly treated with immunochemotherapy.
The current relevant guidelines mainly recommend anti-CD20 monoclonal antibody-based combination chemotherapy, or lenalidomide-based non-chemotherapy
.
The choice of the specific chemotherapy regimen depends on the patient's many factors
.
For older patients with poorer general conditions, the BR regimen or R-CVP regimen can be used; for patients with a higher SUV value or Ki-67 index and a higher probability of disease conversion, the R-CHOP regimen can be used
.
The results of the GALLIUM study show that compared with rituximab combined with chemotherapy, the new anti-CD20 monoclonal antibody otuzumab combined with chemotherapy can further improve the PFS of FL patients
.
At present, the treatment of FL has entered the stage of precision treatment.
The treatment strategy should not be selected simply according to the patient's age and physical condition, but the most suitable treatment plan for FL patients should be selected according to the patient's immune microenvironment and genetic changes
.
Yimaitong: You have done a lot of in-depth research in the field of FL.
Could you please introduce the latest progress in diagnosis and treatment of FL? Although Professor Xu Bing FL is a kind of indolent lymphoma, there has been more progress in related research in recent years
.
For patients with limited-stage FL, related studies have shown that the combination of maintenance therapy with anti-CD20 monoclonal antibody on the basis of radiotherapy alone can further improve the efficacy
.
For patients with advanced FL, the chemotherapy-free regimen of otuzumab combined with lenalidomide left a deep impression on everyone
.
Relevant research results show that the safe remission (CR) rate of this regimen in the treatment of FL patients reaches 94%, and the efficacy is significantly better than traditional immunochemotherapy regimens
.
At the same time, the 2-year PFS of FL patients under the treatment of this program reached 96%, which significantly reduced the risk of early disease progression in FL patients, and is expected to bring significant improvements to the prognosis of high-risk FL patients
.
In addition, related studies have shown that the antibody-conjugated drug Polatuzumab Vedotin combined with octuzumab and venacral regimens for the treatment of FL patients refractory to anti-CD20 mAb or alkylating agents, the overall response rate (ORR) can reach more than 70%, CR The rate can reach more than 50%
.
This program provides a better treatment option for FL patients with early disease progression and high refractory disease
.
With the application of many new drugs and new therapies in recent years, the prognosis of FL patients has been continuously improved
.
However, the current treatment of FL should emphasize standardized treatment and individualized treatment, not the latest treatment is the best treatment
.
The most appropriate curative effect should be selected according to the basic situation of the patient, in order to bring the best curative effect, the best quality of life and the longest survival for the patient
.
Yimaitong: Otuzumab has been approved in China.
What impact does the approval of Otuzumab have on the status of FL treatment? Professor Xu Bing is a new type of anti-CD20 monoclonal antibody, and the ADCC effect of otuzumab is significantly better than that of rituximab
.
For high-risk FL patients, otuzumab can reduce the risk of early disease progression and significantly improve the overall prognosis of FL patients
.
For relapsed and refractory FL, otuzumab has shown a good effect whether it is combined with chemotherapy such as BR regimen or combined with small molecule drugs such as lenalidomide
.
Whether in the initial treatment of FL or in the clinical trials of relapsed and refractory FL, otuzumab has obtained good test results
.
With the approval of otuzumab in China, the treatment effect of domestic FL will be significantly improved, and the prognosis of Chinese FL patients will definitely be significantly improved
.
Yimaitong: Could you please introduce the current status of CLL treatment, and what are the current development directions of CLL treatment worthy of attention? Professor Yang Shenmiao: The treatment of CLL has moved from the "immunochemotherapy era" to the "no chemotherapy era" based on small molecule drugs
.
With the continuous increase of BTK inhibitors in recent years and the continuous optimization of many BTK inhibitors in configuration, it is not difficult for CLL patients to achieve long-term survival.
The long-term survival problem of some high-risk CLL patients has also been well resolved
.
Although many treatment problems of high-risk CLL patients have been resolved, long-term disease control can be achieved
.
However, we are still trying to pursue a complete cure for CLL, that is, CLL patients will not affect their daily life after reaching CR, and will not relapse at the same time
.
At present, many prospective studies are exploring whether the deep remission brought by treatment can keep CLL patients in a long-term disease-free state, and the deep remission achieved through treatment allows patients to effectively and safely stop the drug
.
This is a direction currently being explored in the CLL field
.
Yimaitong: In recent years, the emergence of various new drugs has provided new ideas for the treatment of CLL
.
Could you please tell us what changes have taken place in the treatment strategy of CLL in recent years? Professor Yang Shenmiao: At present, relevant research is exploring whether short-term treatment can bring long-term disease control to CLL patients.
At present, some studies have obtained good results
.
The results of the CLL14 study showed that after 12 months of fixed course of treatment with Venecla combined with the new anti-CD20 monoclonal antibody otuzumab, CLL patients can maintain disease-free status for a long time, and some patients can also maintain minimal residual disease (MRD) Of the negative state
.
The research is still in progress.
It is worth looking forward to whether some low-risk, treatment-sensitive patients can be clinically cured through this treatment plan
.
In addition, the results of the MURANO study show that a 24-month fixed course of venexa and rituximab has also achieved good results in the treatment of relapsed and refractory CLL, and more than 80% of the patients in the study achieved a deep MRD negative state.
.
The results of the GLOW study and the CAPTIVATE study published on ASCO and EHA this year also explored the efficacy of a fixed course of treatment in CLL
.
The results of the study show that a fixed course of ibrutinib combined with Venecla can bring deep disease relief to patients with CLL, and the higher MRD negative rate in the study can translate into survival benefits
.
At present, the new drug combination program with a fixed course of treatment has a good treatment prospect in CLL, and the related combination program is also expected to be approved by the FDA in the near future, which is a research direction worth exploring in the field of CLL in recent years
.
Yimaitong: In view of the excellent efficacy of otuzumab in CLL, what do you think is the significance of the application of otuzumab for CLL patients? Professor Yang Shenmiao: Otuzumab has shown excellent tumor clearance ability in CLL
.
The CLL11 study compared the efficacy of otuzumab combined with chlorambucil and rituximab combined with chlorambucil in CLL.
The results of the study showed that the combination of otuzumab can bring additional survival gains.
Benefit
.
The FDA also approved otuzumab combined with chlorambucil for the first-line treatment of CLL as early as 2013, making otuzumab the first anti-tumor drug approved by the FDA through a breakthrough therapy pathway
.
In addition to chlorambucil, the combination of otuzumab and other drugs such as Venecla, Acalabrutinib has also achieved good results in the first-line treatment of CLL
.
Although the current treatment of CLL includes many new drugs, the emergence of many new drugs has also brought new problems to the treatment of CLL, that is, it is more difficult to choose treatment for relapsed and refractory patients who cannot obtain remission after treatment with new drugs.
.
As a new type of anti-CD20 monoclonal antibody, otuzumab can bring clinical benefits to these patients with relapsed and refractory CLL through different mechanisms
.
Relevant research results published on EHA and ASH this year also show that for CLL patients who are resistant to Ibrutinib treatment, the treatment of otuzumab can still benefit these patients
.
Therefore, it is expected that Otuzumab will be approved for CLL-related indications in China as soon as possible, bringing new treatment options to patients with newly treated and relapsed and refractory CLL, improving the quality of life of CLL patients, and prolonging the survival of CLL patients
.
Professor Xu Bing, a second-level chief physician, professor, and doctoral supervisor, Director of the Department of Hematology, Xiamen University, Director of the Department of Hematology, Xiamen University, Director of the First Affiliated Hospital of Xiamen University, Director of the Department of Hematology and Director of the Department of Internal Medicine, Director of Internal Medicine Training Base, Leader of Chinese Follicular Lymphoma Working Group, Chairman of Leukemia Academic Working Committee of Chinese Society of Geriatrics, Member of Standing Committee of Hematology and Oncology Professional Committee of Chinese Anti-Cancer Association, Standing Committee of Lymphoma Professional Committee of Chinese Anti-Cancer Association, won the first prize of provincial and ministerial scientific and technological progress 1 prize, 3 second prizes, presided over 4 National Natural Science Foundation of China, published more than 200 papers as the first or corresponding author, including 60 SCI papers, 20 papers with a score of 5 or more, and a total impact factor of more than 200.
Professor Yang Shenmiao Doctor of Medicine, Associate Chief Physician, Peking University Institute of Hematology, Associate Chief Physician, Member of Beijing Association of Integrative Medicine and Hematology, Member of Lymphoma Group, Oncology Branch of Chinese Medical Association, Member of Lymphhematology, Chinese Society of Geriatric Oncology, Youth Committee of Lymphology and Hematology, Chinese Society of Geriatric Cancer Professional Committee (CSCO) Member of the Chinese Anti-Lymphoma Alliance Member of the First Chinese Chronic Lymphocytic Leukemia Working Group (cwCLL) Committee of the Hematological Oncology Professional Committee of the Chinese Anti-Cancer Association.
Main professional direction: Lymphatic system proliferative diseases include: malignant lymphoma, chronic lymphoma Cell leukemia and other stamps "read the original", we make progress together
.
This forum brought together many outstanding leukemia and lymphoma experts at home and abroad, and will conduct in-depth discussions and exchanges on new drug development and clinical applications
.
Yimaitong has the honor to invite Professor Xu Bing from the First Affiliated Hospital of Xiamen University and Professor Yang Shenmiao from Peking University People’s Hospital to discuss the new anti-CD20 monoclonal antibody otuzumab in follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL).
) To share the application prospects
.
Yimaitong: First of all, could you please introduce how you give individualized treatment to patients with FL? Professor Xu Bing currently implements stratified treatment for FL according to the stage of the disease.
For patients with stage I or limited stage II FL, nearly 50% of patients can be cured by radiotherapy-based treatment
.
Some patients can be combined with anti-CD20 monoclonal antibody on the basis of radiotherapy to further improve the efficacy and reduce the recurrence rate and disease conversion rate
.
However, the proportion of stage I and limited stage II patients is relatively small, accounting for only 10% of FL
.
Most FL patients are non-limited stage II or III/IV patients.
For this part of FL patients, treatment stratification depends on whether there are indications for treatment
.
For FL patients who are not indicated for treatment, a "watchful and waiting" treatment strategy can be adopted, and treatment can be carried out after the disease has progressed
.
FL patients with indications for treatment are mainly treated with immunochemotherapy.
The current relevant guidelines mainly recommend anti-CD20 monoclonal antibody-based combination chemotherapy, or lenalidomide-based non-chemotherapy
.
The choice of the specific chemotherapy regimen depends on the patient's many factors
.
For older patients with poorer general conditions, the BR regimen or R-CVP regimen can be used; for patients with a higher SUV value or Ki-67 index and a higher probability of disease conversion, the R-CHOP regimen can be used
.
The results of the GALLIUM study show that compared with rituximab combined with chemotherapy, the new anti-CD20 monoclonal antibody otuzumab combined with chemotherapy can further improve the PFS of FL patients
.
At present, the treatment of FL has entered the stage of precision treatment.
The treatment strategy should not be selected simply according to the patient's age and physical condition, but the most suitable treatment plan for FL patients should be selected according to the patient's immune microenvironment and genetic changes
.
Yimaitong: You have done a lot of in-depth research in the field of FL.
Could you please introduce the latest progress in diagnosis and treatment of FL? Although Professor Xu Bing FL is a kind of indolent lymphoma, there has been more progress in related research in recent years
.
For patients with limited-stage FL, related studies have shown that the combination of maintenance therapy with anti-CD20 monoclonal antibody on the basis of radiotherapy alone can further improve the efficacy
.
For patients with advanced FL, the chemotherapy-free regimen of otuzumab combined with lenalidomide left a deep impression on everyone
.
Relevant research results show that the safe remission (CR) rate of this regimen in the treatment of FL patients reaches 94%, and the efficacy is significantly better than traditional immunochemotherapy regimens
.
At the same time, the 2-year PFS of FL patients under the treatment of this program reached 96%, which significantly reduced the risk of early disease progression in FL patients, and is expected to bring significant improvements to the prognosis of high-risk FL patients
.
In addition, related studies have shown that the antibody-conjugated drug Polatuzumab Vedotin combined with octuzumab and venacral regimens for the treatment of FL patients refractory to anti-CD20 mAb or alkylating agents, the overall response rate (ORR) can reach more than 70%, CR The rate can reach more than 50%
.
This program provides a better treatment option for FL patients with early disease progression and high refractory disease
.
With the application of many new drugs and new therapies in recent years, the prognosis of FL patients has been continuously improved
.
However, the current treatment of FL should emphasize standardized treatment and individualized treatment, not the latest treatment is the best treatment
.
The most appropriate curative effect should be selected according to the basic situation of the patient, in order to bring the best curative effect, the best quality of life and the longest survival for the patient
.
Yimaitong: Otuzumab has been approved in China.
What impact does the approval of Otuzumab have on the status of FL treatment? Professor Xu Bing is a new type of anti-CD20 monoclonal antibody, and the ADCC effect of otuzumab is significantly better than that of rituximab
.
For high-risk FL patients, otuzumab can reduce the risk of early disease progression and significantly improve the overall prognosis of FL patients
.
For relapsed and refractory FL, otuzumab has shown a good effect whether it is combined with chemotherapy such as BR regimen or combined with small molecule drugs such as lenalidomide
.
Whether in the initial treatment of FL or in the clinical trials of relapsed and refractory FL, otuzumab has obtained good test results
.
With the approval of otuzumab in China, the treatment effect of domestic FL will be significantly improved, and the prognosis of Chinese FL patients will definitely be significantly improved
.
Yimaitong: Could you please introduce the current status of CLL treatment, and what are the current development directions of CLL treatment worthy of attention? Professor Yang Shenmiao: The treatment of CLL has moved from the "immunochemotherapy era" to the "no chemotherapy era" based on small molecule drugs
.
With the continuous increase of BTK inhibitors in recent years and the continuous optimization of many BTK inhibitors in configuration, it is not difficult for CLL patients to achieve long-term survival.
The long-term survival problem of some high-risk CLL patients has also been well resolved
.
Although many treatment problems of high-risk CLL patients have been resolved, long-term disease control can be achieved
.
However, we are still trying to pursue a complete cure for CLL, that is, CLL patients will not affect their daily life after reaching CR, and will not relapse at the same time
.
At present, many prospective studies are exploring whether the deep remission brought by treatment can keep CLL patients in a long-term disease-free state, and the deep remission achieved through treatment allows patients to effectively and safely stop the drug
.
This is a direction currently being explored in the CLL field
.
Yimaitong: In recent years, the emergence of various new drugs has provided new ideas for the treatment of CLL
.
Could you please tell us what changes have taken place in the treatment strategy of CLL in recent years? Professor Yang Shenmiao: At present, relevant research is exploring whether short-term treatment can bring long-term disease control to CLL patients.
At present, some studies have obtained good results
.
The results of the CLL14 study showed that after 12 months of fixed course of treatment with Venecla combined with the new anti-CD20 monoclonal antibody otuzumab, CLL patients can maintain disease-free status for a long time, and some patients can also maintain minimal residual disease (MRD) Of the negative state
.
The research is still in progress.
It is worth looking forward to whether some low-risk, treatment-sensitive patients can be clinically cured through this treatment plan
.
In addition, the results of the MURANO study show that a 24-month fixed course of venexa and rituximab has also achieved good results in the treatment of relapsed and refractory CLL, and more than 80% of the patients in the study achieved a deep MRD negative state.
.
The results of the GLOW study and the CAPTIVATE study published on ASCO and EHA this year also explored the efficacy of a fixed course of treatment in CLL
.
The results of the study show that a fixed course of ibrutinib combined with Venecla can bring deep disease relief to patients with CLL, and the higher MRD negative rate in the study can translate into survival benefits
.
At present, the new drug combination program with a fixed course of treatment has a good treatment prospect in CLL, and the related combination program is also expected to be approved by the FDA in the near future, which is a research direction worth exploring in the field of CLL in recent years
.
Yimaitong: In view of the excellent efficacy of otuzumab in CLL, what do you think is the significance of the application of otuzumab for CLL patients? Professor Yang Shenmiao: Otuzumab has shown excellent tumor clearance ability in CLL
.
The CLL11 study compared the efficacy of otuzumab combined with chlorambucil and rituximab combined with chlorambucil in CLL.
The results of the study showed that the combination of otuzumab can bring additional survival gains.
Benefit
.
The FDA also approved otuzumab combined with chlorambucil for the first-line treatment of CLL as early as 2013, making otuzumab the first anti-tumor drug approved by the FDA through a breakthrough therapy pathway
.
In addition to chlorambucil, the combination of otuzumab and other drugs such as Venecla, Acalabrutinib has also achieved good results in the first-line treatment of CLL
.
Although the current treatment of CLL includes many new drugs, the emergence of many new drugs has also brought new problems to the treatment of CLL, that is, it is more difficult to choose treatment for relapsed and refractory patients who cannot obtain remission after treatment with new drugs.
.
As a new type of anti-CD20 monoclonal antibody, otuzumab can bring clinical benefits to these patients with relapsed and refractory CLL through different mechanisms
.
Relevant research results published on EHA and ASH this year also show that for CLL patients who are resistant to Ibrutinib treatment, the treatment of otuzumab can still benefit these patients
.
Therefore, it is expected that Otuzumab will be approved for CLL-related indications in China as soon as possible, bringing new treatment options to patients with newly treated and relapsed and refractory CLL, improving the quality of life of CLL patients, and prolonging the survival of CLL patients
.
Professor Xu Bing, a second-level chief physician, professor, and doctoral supervisor, Director of the Department of Hematology, Xiamen University, Director of the Department of Hematology, Xiamen University, Director of the First Affiliated Hospital of Xiamen University, Director of the Department of Hematology and Director of the Department of Internal Medicine, Director of Internal Medicine Training Base, Leader of Chinese Follicular Lymphoma Working Group, Chairman of Leukemia Academic Working Committee of Chinese Society of Geriatrics, Member of Standing Committee of Hematology and Oncology Professional Committee of Chinese Anti-Cancer Association, Standing Committee of Lymphoma Professional Committee of Chinese Anti-Cancer Association, won the first prize of provincial and ministerial scientific and technological progress 1 prize, 3 second prizes, presided over 4 National Natural Science Foundation of China, published more than 200 papers as the first or corresponding author, including 60 SCI papers, 20 papers with a score of 5 or more, and a total impact factor of more than 200.
Professor Yang Shenmiao Doctor of Medicine, Associate Chief Physician, Peking University Institute of Hematology, Associate Chief Physician, Member of Beijing Association of Integrative Medicine and Hematology, Member of Lymphoma Group, Oncology Branch of Chinese Medical Association, Member of Lymphhematology, Chinese Society of Geriatric Oncology, Youth Committee of Lymphology and Hematology, Chinese Society of Geriatric Cancer Professional Committee (CSCO) Member of the Chinese Anti-Lymphoma Alliance Member of the First Chinese Chronic Lymphocytic Leukemia Working Group (cwCLL) Committee of the Hematological Oncology Professional Committee of the Chinese Anti-Cancer Association.
Main professional direction: Lymphatic system proliferative diseases include: malignant lymphoma, chronic lymphoma Cell leukemia and other stamps "read the original", we make progress together
