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In recent years, the treatment strategies of hematological tumors have changed rapidly, and many progresses have been made in both theory and clinical practice
.
Nowadays, most patients with B-cell lymphoma can achieve long-term survival, but they are still faced with the treatment dilemma of incurable and high recurrence rate, and the treatment needs of patients need to be met urgently
.
Based on clinical needs and focusing on the treatment progress of B-cell lymphoma, Yimaitong specially invited Professor Li Yuhua of Pearl River Hospital of Southern Medical University and Professor Li Wenyu of Guangdong Provincial People's Hospital to be interviewed to share the treatment strategy of B-cell lymphoma in the era of new drugs
.
Yimaitong: Could you please discuss the current status of B-cell lymphoma treatment in my country based on your clinical experience? Professor Li Yuhua Since the launch of rituximab in the late 1990s, immunotherapy has become an indispensable part of the treatment of malignant lymphoma, especially B-cell lymphoma.
With the continuous emergence of new immunotherapy drugs, B-cell lymphoma Cancer has entered a new era of immunotherapy
.
B-cell lymphomas can be classified into three types based on their natural history, namely indolent, aggressive, and highly aggressive lymphomas
.
In clinical practice, some aggressive B-cell lymphomas can be cured by chemotherapy or targeted therapy.
For example, nearly half of the most common diffuse large B-cell lymphoma (DLBCL) can be cured, but 30%-50% are still cured.
of patients with refractory or relapse (R/R); although indolent lymphoma can be controlled by disease progression, it is still incurable, prone to repeated recurrence, and each recurrence is accompanied by a shortened survival period and significantly reduced quality of life
.
Nevertheless, clinicians still hope to further improve the cure rate of aggressive lymphoma and improve the quality of life of patients with indolent lymphoma, so that they can live the same life as their peers
.
Professor Li Wenyu has increased the incidence of B-cell lymphoma year by year in recent years.
In the past 15 years, the clinical trials of new anti-lymphoma drugs in China have made great progress, and patients have more treatment options, but their survival still needs to be improved
.
The latest data show that in 2020, there will be about 93,000 new non-Hodgkin lymphoma (NHL) patients in China and 54,000 deaths
.
As a lymphoma specialist, our department has about 400 new cases of lymphoma every year, more than half of which are B-cell lymphomas.
The number of patients with indolent lymphomas has also increased in recent years, but there is still no cure
.
In recent years, the treatment of indolent lymphoma has progressed rapidly, and new drugs represented by the new generation of anti-CD20 monoclonal antibody otuzumab have shown excellent efficacy and safety.
It is believed that with the continuous emergence of new drugs, immunotherapy drugs combined with small molecules Targeted drugs may replace traditional chemotherapy and become the main means of B-cell lymphoma treatment
.
Yimaitong: As you said, the emergence of many new drugs has greatly improved the efficacy of B-cell lymphoma, but over time, patients tend to relapse, which ultimately leads to an increased chance of refractory treatment
.
How to improve the curative effect and survival of patients with relapsed/refractory B-cell lymphoma is also a current research hotspot.
Could you share with us the progress worthy of attention in the treatment of relapsed/refractory B-cell lymphoma? Professor Li Yuhua took the most common indolent lymphoma FL as an example.
Foreign studies have shown that although the overall prognosis of FL patients is good, 20% of FL patients still progress or relapse within 2 years after starting first-line therapy (POD24), and 10%-70% of FL patients During the course of the disease, it transforms to highly aggressive lymphoma, and the annual transformation rate is 3%.
The prognosis of these two types of patients is poor
.
The incidence of POD24 in Chinese patients may be higher than that in the West.
A domestic single-center analysis published in the Journal of Clinical Hematology recently showed that 24.
1% of FL patients will relapse and progress within 2 years.
The treatment plan has been greatly improved compared with the previous era of simple radiotherapy and chemotherapy, but it is still necessary to pay attention to the problem of relapse and refractory
.
Improving the remission rate and survival outcome of relapsed patients is also one of the main directions to explore new treatment options
.
LYSA Phase II Clinical Study Evaluating Ortuzumab (GA101) + Venetoclax + Atezolizumab in the Treatment of R/RB Cell Lymphomas (including FL/Marginal Zone Lymphoma [MZL]) ) efficacy and safety
.
With a median follow-up of 14.
5 months in the FL cohort (n=58), the ORR was 53.
6%, of which 30.
4% had a molecular response (CMR)
.
The median follow-up time of the MZL cohort (n=20) was 11.
9 months, and the ORR was 66.
76% (complete response [CR] 16.
7%, partial response [PR] 50%)
.
The efficacy of this multicenter study was durable in both the R/R FL and MZL cohorts, with only 21.
4% of patients experiencing relapse/progression
.
There were no unexpected toxicities associated with the triple regimen
.
The G-Ven-Ate triple therapy regimen was well tolerated and did not cause unexpected toxicities
.
Compared with other novel treatment regimens, the ORR at the end of induction seems to be comparable to other novel regimens with durable remissions so far, and we look forward to the future application of this combination regimen in B-cell lymphoma
.
Professor Li Wenyu of Ortuzumab combined with lenalidomide (Glen) has shown clinically meaningful efficacy in both newly treated FL and relapsed and refractory FL.
In newly treated FL, the 2-year PFS rate can be as high as 96%; In relapsed and refractory FL, the 2-year PFS rate can reach 74%, which is expected to bring a better chemotherapy-free regimen for FL patients
.
The Glen regimen is also a viable treatment option for previously rituximab-refractory FL patients
.
With the deepening of research, it is hoped that indolent lymphoma can become a chronic disease, improve the deep remission rate, prolong the disease stabilization and control time of patients, improve the quality of life of patients, prolong the OS of patients, and even achieve cure
.
Yimaitong: Research such as CLL14 has also brought new hope for the treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) patients.
Could you please discuss this topic in depth? In the field of CLL treatment, Professor Li Wenyu has mainly focused on BTK inhibitors, BCL-2 inhibitors, PI3K inhibitors, and the new humanized anti-CD20 monoclonal antibody octuzumab in the past two years.
Although the curative effect is good, patients in the real world often discontinue the drug due to adverse reactions, and their living conditions are often not as good as in clinical trials.
Therefore, it is very expected that the fixed course of CLL will be widely used in the real world in the future
.
The latest efficacy and safety data from the CLL14 study show that a fixed course of veneclax plus octuzumab resulted in a longer PFS and higher than chlorambucil plus octuzumab deep remission rate
.
The majority of patients had not relapsed three years after completing veneclax plus octuzumab
.
Although patients with poor prognosis such as TP53 mutation/deletion still have poor prognosis, a fixed course of veneclax combined with octuzumab is still an effective treatment option for treatment-naïve patients with comorbid CLL
.
For young patients, we hope that through a fixed course of treatment, patients can better return to normal work and life; for elderly patients, the long-term toxic and side effects caused by taking targeted drugs all year round can be reduced.
The treatment landscape for SLL has changed dramatically
.
Yimaitong: Could you please share your experience in the clinical application of otuzumab and talk about your prospects for the treatment of B-cell lymphoma? Prof.
Li Yuhua's first approved indication for ortuzumab in China this year is FL, but the drug has been used abroad for 8 years, and both efficacy and safety have shown significant benefits
.
At present, 2 patients in our department have received octuzumab infusion, and the safety of the infusion process is good.
At present, these 2 patients are still under evaluation of efficacy.
Combined with previous octuzumab-related studies, the efficacy has been significantly improved.
It is believed that otuzumab-based therapy can become the preferred treatment for patients with B-cell lymphoma
.
Accessibility and standardized use are synchronized.
Since the approval of octuzumab, the Lymphoma Expert Committee of the Chinese Society of Clinical Oncology (CSCO) has started to launch the "Chinese Expert Consensus on the Guiding Principles of Clinical Drug Use of Otuzumab (2021 Edition)" The formulation of the drug, taking into account the existing domestic and foreign clinical research evidence and clinical practice in China, has carried out a detailed interpretation from the mechanism of action, usage and dosage, and effectiveness research.
This greatly increased accessibility is expected to help patients maximize clinical benefit
.
Professor Li Wenyu's current drug research on lymphoma mainly focuses on the targeted therapy of surface antigens, signaling pathways in the pathogenesis of lymphoma cells, and regulation of immune microenvironment
.
In order to improve survival and tolerance, the treatment mode of FL has gradually focused on targeted and immune drugs.
More and more newly diagnosed patients are cured from first-line treatment, and R/R patients also have more choices and attempts.
opportunity, the era of "chemo-free" is just around the corner
.
Now the remission rate of CAR-T cell therapy is also very high, but the follow-up relapse problem also needs to be considered in combination with new drugs, and the combined use of otuzumab for maintenance therapy is also an explorable direction
.
In addition to indolent lymphoma, clinicians are also concerned with highly aggressive DLBCL
.
The number of DLBCL cases in provincial tertiary hospitals accounts for 30%-40% of the total number of lymphomas, and it may be higher in county/city/district hospitals
.
The CAR-T cell therapy that everyone is concerned about now can cure 30%-40% of patients with relapsed and refractory DLBCL.
In addition, antibody drug conjugates (ADCs) and bispecific antibodies have also entered a stage of rapid development.
The trials are in full swing in China.
It is believed that the new anti-tumor drugs will show explosive growth in the next two years, allowing more lymphoma patients to achieve long-term survival and improve their quality of life
.
Professor Li Yuhua, Chief Physician, Professor, Doctor of Medicine, Post-doctoral Supervisor, Director of the Department of Hematology, Pearl River Hospital, Southern Medical University Member of the Cell Therapy Group of the Professional Committee of Hematology and Cancer Chairman of the Professional Committee of Guangdong Provincial Institute of Immunology Deputy Chairman of the Professional Committee of Clinical Immunology of Guangdong Provincial Association of Immunology Professor Chang Li Wenyu of the 17th Council of the Guangdong Provincial Pharmaceutical Association Hematology Drug Expert Committee Chief Physician, Master Supervisor, Doctor of Medicine Guangdong Provincial People's Hospital Administrative Director of the Lymphoma Department of the Center Chairman of the Lymphoma Professional Committee of the Guangdong Women's Physician Association Vice Chairman of the Medical Oncology Branch of the Guangdong Medical Association Vice Chairman of the Guangzhou Hematology and Oncology Professional Committee Vice Chairman of the Lymphoma Professional Committee of the Guangzhou Anti-Cancer Association Association Member CACA Youth Committee ★ Scan the QR code below to enter the "Mystery Exploration" channel ★ Click "Read the original text" to enter the "Mystery Exploration" channel!
.
Nowadays, most patients with B-cell lymphoma can achieve long-term survival, but they are still faced with the treatment dilemma of incurable and high recurrence rate, and the treatment needs of patients need to be met urgently
.
Based on clinical needs and focusing on the treatment progress of B-cell lymphoma, Yimaitong specially invited Professor Li Yuhua of Pearl River Hospital of Southern Medical University and Professor Li Wenyu of Guangdong Provincial People's Hospital to be interviewed to share the treatment strategy of B-cell lymphoma in the era of new drugs
.
Yimaitong: Could you please discuss the current status of B-cell lymphoma treatment in my country based on your clinical experience? Professor Li Yuhua Since the launch of rituximab in the late 1990s, immunotherapy has become an indispensable part of the treatment of malignant lymphoma, especially B-cell lymphoma.
With the continuous emergence of new immunotherapy drugs, B-cell lymphoma Cancer has entered a new era of immunotherapy
.
B-cell lymphomas can be classified into three types based on their natural history, namely indolent, aggressive, and highly aggressive lymphomas
.
In clinical practice, some aggressive B-cell lymphomas can be cured by chemotherapy or targeted therapy.
For example, nearly half of the most common diffuse large B-cell lymphoma (DLBCL) can be cured, but 30%-50% are still cured.
of patients with refractory or relapse (R/R); although indolent lymphoma can be controlled by disease progression, it is still incurable, prone to repeated recurrence, and each recurrence is accompanied by a shortened survival period and significantly reduced quality of life
.
Nevertheless, clinicians still hope to further improve the cure rate of aggressive lymphoma and improve the quality of life of patients with indolent lymphoma, so that they can live the same life as their peers
.
Professor Li Wenyu has increased the incidence of B-cell lymphoma year by year in recent years.
In the past 15 years, the clinical trials of new anti-lymphoma drugs in China have made great progress, and patients have more treatment options, but their survival still needs to be improved
.
The latest data show that in 2020, there will be about 93,000 new non-Hodgkin lymphoma (NHL) patients in China and 54,000 deaths
.
As a lymphoma specialist, our department has about 400 new cases of lymphoma every year, more than half of which are B-cell lymphomas.
The number of patients with indolent lymphomas has also increased in recent years, but there is still no cure
.
In recent years, the treatment of indolent lymphoma has progressed rapidly, and new drugs represented by the new generation of anti-CD20 monoclonal antibody otuzumab have shown excellent efficacy and safety.
It is believed that with the continuous emergence of new drugs, immunotherapy drugs combined with small molecules Targeted drugs may replace traditional chemotherapy and become the main means of B-cell lymphoma treatment
.
Yimaitong: As you said, the emergence of many new drugs has greatly improved the efficacy of B-cell lymphoma, but over time, patients tend to relapse, which ultimately leads to an increased chance of refractory treatment
.
How to improve the curative effect and survival of patients with relapsed/refractory B-cell lymphoma is also a current research hotspot.
Could you share with us the progress worthy of attention in the treatment of relapsed/refractory B-cell lymphoma? Professor Li Yuhua took the most common indolent lymphoma FL as an example.
Foreign studies have shown that although the overall prognosis of FL patients is good, 20% of FL patients still progress or relapse within 2 years after starting first-line therapy (POD24), and 10%-70% of FL patients During the course of the disease, it transforms to highly aggressive lymphoma, and the annual transformation rate is 3%.
The prognosis of these two types of patients is poor
.
The incidence of POD24 in Chinese patients may be higher than that in the West.
A domestic single-center analysis published in the Journal of Clinical Hematology recently showed that 24.
1% of FL patients will relapse and progress within 2 years.
The treatment plan has been greatly improved compared with the previous era of simple radiotherapy and chemotherapy, but it is still necessary to pay attention to the problem of relapse and refractory
.
Improving the remission rate and survival outcome of relapsed patients is also one of the main directions to explore new treatment options
.
LYSA Phase II Clinical Study Evaluating Ortuzumab (GA101) + Venetoclax + Atezolizumab in the Treatment of R/RB Cell Lymphomas (including FL/Marginal Zone Lymphoma [MZL]) ) efficacy and safety
.
With a median follow-up of 14.
5 months in the FL cohort (n=58), the ORR was 53.
6%, of which 30.
4% had a molecular response (CMR)
.
The median follow-up time of the MZL cohort (n=20) was 11.
9 months, and the ORR was 66.
76% (complete response [CR] 16.
7%, partial response [PR] 50%)
.
The efficacy of this multicenter study was durable in both the R/R FL and MZL cohorts, with only 21.
4% of patients experiencing relapse/progression
.
There were no unexpected toxicities associated with the triple regimen
.
The G-Ven-Ate triple therapy regimen was well tolerated and did not cause unexpected toxicities
.
Compared with other novel treatment regimens, the ORR at the end of induction seems to be comparable to other novel regimens with durable remissions so far, and we look forward to the future application of this combination regimen in B-cell lymphoma
.
Professor Li Wenyu of Ortuzumab combined with lenalidomide (Glen) has shown clinically meaningful efficacy in both newly treated FL and relapsed and refractory FL.
In newly treated FL, the 2-year PFS rate can be as high as 96%; In relapsed and refractory FL, the 2-year PFS rate can reach 74%, which is expected to bring a better chemotherapy-free regimen for FL patients
.
The Glen regimen is also a viable treatment option for previously rituximab-refractory FL patients
.
With the deepening of research, it is hoped that indolent lymphoma can become a chronic disease, improve the deep remission rate, prolong the disease stabilization and control time of patients, improve the quality of life of patients, prolong the OS of patients, and even achieve cure
.
Yimaitong: Research such as CLL14 has also brought new hope for the treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) patients.
Could you please discuss this topic in depth? In the field of CLL treatment, Professor Li Wenyu has mainly focused on BTK inhibitors, BCL-2 inhibitors, PI3K inhibitors, and the new humanized anti-CD20 monoclonal antibody octuzumab in the past two years.
Although the curative effect is good, patients in the real world often discontinue the drug due to adverse reactions, and their living conditions are often not as good as in clinical trials.
Therefore, it is very expected that the fixed course of CLL will be widely used in the real world in the future
.
The latest efficacy and safety data from the CLL14 study show that a fixed course of veneclax plus octuzumab resulted in a longer PFS and higher than chlorambucil plus octuzumab deep remission rate
.
The majority of patients had not relapsed three years after completing veneclax plus octuzumab
.
Although patients with poor prognosis such as TP53 mutation/deletion still have poor prognosis, a fixed course of veneclax combined with octuzumab is still an effective treatment option for treatment-naïve patients with comorbid CLL
.
For young patients, we hope that through a fixed course of treatment, patients can better return to normal work and life; for elderly patients, the long-term toxic and side effects caused by taking targeted drugs all year round can be reduced.
The treatment landscape for SLL has changed dramatically
.
Yimaitong: Could you please share your experience in the clinical application of otuzumab and talk about your prospects for the treatment of B-cell lymphoma? Prof.
Li Yuhua's first approved indication for ortuzumab in China this year is FL, but the drug has been used abroad for 8 years, and both efficacy and safety have shown significant benefits
.
At present, 2 patients in our department have received octuzumab infusion, and the safety of the infusion process is good.
At present, these 2 patients are still under evaluation of efficacy.
Combined with previous octuzumab-related studies, the efficacy has been significantly improved.
It is believed that otuzumab-based therapy can become the preferred treatment for patients with B-cell lymphoma
.
Accessibility and standardized use are synchronized.
Since the approval of octuzumab, the Lymphoma Expert Committee of the Chinese Society of Clinical Oncology (CSCO) has started to launch the "Chinese Expert Consensus on the Guiding Principles of Clinical Drug Use of Otuzumab (2021 Edition)" The formulation of the drug, taking into account the existing domestic and foreign clinical research evidence and clinical practice in China, has carried out a detailed interpretation from the mechanism of action, usage and dosage, and effectiveness research.
This greatly increased accessibility is expected to help patients maximize clinical benefit
.
Professor Li Wenyu's current drug research on lymphoma mainly focuses on the targeted therapy of surface antigens, signaling pathways in the pathogenesis of lymphoma cells, and regulation of immune microenvironment
.
In order to improve survival and tolerance, the treatment mode of FL has gradually focused on targeted and immune drugs.
More and more newly diagnosed patients are cured from first-line treatment, and R/R patients also have more choices and attempts.
opportunity, the era of "chemo-free" is just around the corner
.
Now the remission rate of CAR-T cell therapy is also very high, but the follow-up relapse problem also needs to be considered in combination with new drugs, and the combined use of otuzumab for maintenance therapy is also an explorable direction
.
In addition to indolent lymphoma, clinicians are also concerned with highly aggressive DLBCL
.
The number of DLBCL cases in provincial tertiary hospitals accounts for 30%-40% of the total number of lymphomas, and it may be higher in county/city/district hospitals
.
The CAR-T cell therapy that everyone is concerned about now can cure 30%-40% of patients with relapsed and refractory DLBCL.
In addition, antibody drug conjugates (ADCs) and bispecific antibodies have also entered a stage of rapid development.
The trials are in full swing in China.
It is believed that the new anti-tumor drugs will show explosive growth in the next two years, allowing more lymphoma patients to achieve long-term survival and improve their quality of life
.
Professor Li Yuhua, Chief Physician, Professor, Doctor of Medicine, Post-doctoral Supervisor, Director of the Department of Hematology, Pearl River Hospital, Southern Medical University Member of the Cell Therapy Group of the Professional Committee of Hematology and Cancer Chairman of the Professional Committee of Guangdong Provincial Institute of Immunology Deputy Chairman of the Professional Committee of Clinical Immunology of Guangdong Provincial Association of Immunology Professor Chang Li Wenyu of the 17th Council of the Guangdong Provincial Pharmaceutical Association Hematology Drug Expert Committee Chief Physician, Master Supervisor, Doctor of Medicine Guangdong Provincial People's Hospital Administrative Director of the Lymphoma Department of the Center Chairman of the Lymphoma Professional Committee of the Guangdong Women's Physician Association Vice Chairman of the Medical Oncology Branch of the Guangdong Medical Association Vice Chairman of the Guangzhou Hematology and Oncology Professional Committee Vice Chairman of the Lymphoma Professional Committee of the Guangzhou Anti-Cancer Association Association Member CACA Youth Committee ★ Scan the QR code below to enter the "Mystery Exploration" channel ★ Click "Read the original text" to enter the "Mystery Exploration" channel!
