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In 1982, the working classification of lymphoma first proposed the concept of "indolent lymphoma".
Although there is no cure for indolent lymphoma at present, looking back over the past three decades, with the continuous emergence of new drugs, the treatment mode of indolent lymphoma has undergone tremendous changes.
The patient's survival has improved significantly
.
Yimaitong specially invited Professor Jin Zhengming from the Department of Hematology of the First Affiliated Hospital of Soochow University and Professor Wang Li of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine for an interview, reviewing the development history of indolent lymphoma, and learning from indolent lymphoma based on the current clinical practice.
The pioneering spirit of hard work, in order to benefit more laziness patients
.
Yi Mai Tong: First of all, please review the treatment mode of indolent lymphoma and the survival status of patients before the advent of rituximab
.
Before the advent of rituximab by Professor Jin Zhengming, the main treatment for indolent lymphoma was chemotherapy, which we call the era of chemotherapy.
From the beginning of single-agent chemotherapy, it gradually developed into multi-drug combination chemotherapy.
Treatment presents many serious challenges
.
The first is chemotherapy-related adverse reactions.
Patients with indolent lymphoma are often older and have poor tolerance to chemotherapy.
Second, whether increasing the dose of chemotherapy or combining chemotherapy drugs, it seems that the survival of patients cannot be significantly improved.
More adverse reactions; in addition, for patients with indolent lymphoma with low tumor burden, aggressive chemotherapy regimens cannot significantly improve patient survival, so "watch and wait" therapy is the preferred treatment for patients with indolent lymphoma.
After the patient develops symptoms, the chemotherapy regimen is formulated according to the individual situation
.
Yi Mai Tong: Rituximab, as a milestone drug in the field of lymphoma, has established an unshakable position in just a few decades
.
How did rituximab revolutionize the treatment paradigm for indolent lymphoma? Professor Wang Li's breakthroughs in indolent lymphoma signal transduction pathways and anti-tumor immune responses, especially in the research of non-cytotoxic drugs, support the development of tumor immunity
.
Rituximab is an epoch-making drug in the treatment of indolent lymphoma
.
The application of rituximab in indolent lymphoma is also a process of gradual exploration, which is mainly divided into two stages
.
Rituximab single-agent induction vs waiting and observation: As Professor Jin Zhengming said, for patients with indolent lymphoma with low tumor burden, the first choice is to wait and observe treatment in the early stage
.
A study in the United Kingdom in asymptomatic and mass-free stage II, III, and IV FL-naïve patients compared watchful waiting with rituximab single-agent induction, rituximab single-agent induction + maintenance Efficacy among the three groups
.
The recent (7-month) remission rate increased significantly from 6% to 74% and 88%, respectively (p<0.
01); the 3-year progression-free survival rate increased significantly from 33% to 60% and 81%, respectively (p<0.
01).
And rituximab treatment also significantly delayed the time to receive chemotherapy or radiation
.
Rituximab combined with chemotherapy vs traditional chemotherapy: In the past, chemotherapy-based treatment of indolent lymphoma has achieved remission, but it is difficult to prolong the overall survival (OS) of patients
.
After the emergence of rituximab, a number of clinical studies have shown that rituximab combined with various chemotherapy regimens (including CVP, CHOP, etc.
) in the first-line treatment of FL have shown long-term survival benefits
.
Three pivotal studies of R in the treatment of FL: GLSG2000, M39021, and M39023, respectively compared the efficacy of chemotherapy combined with targeted therapy and chemotherapy alone in newly treated patients
.
The results showed that the survival rate of patients in the R-chemo (R combined with chemotherapy) group was improved compared with the patients in the chemotherapy alone group, and there was a significant difference in overall survival
.
On this basis, the Eastern Cooperative Oncology Group (ECOG) conducted the ECOG1496 study in treatment-naïve FL patients, revealing that rituximab maintenance therapy can benefit FL patients
.
So far, rituximab-based immunochemotherapy has become the first-line treatment of FL, and we call this period the era of immunochemotherapy
.
Yimaitong: In order to improve the efficacy and drug safety of indolent lymphoma, what other explorations have been made by workers in this field? Professor Wang Li's therapeutic exploration in the field of indolent lymphoma has never stopped
.
In the exploration of chemotherapy drugs, rituximab combined with bendamustine can effectively improve the treatment effect of patients, reduce recurrence, and in terms of adverse reactions, it can significantly reduce myelosuppression and cardiotoxicity compared with the R-CHOP regimen.
.
In terms of monoclonal antibody exploration, in preclinical studies, the type II humanized anti-CD20 monoclonal antibody octuzumab has been shown to have stronger antibody-dependent cell-mediated effects than murine rituximab Cytotoxicity (ADCC) and phagocytosis (ADCP), lower complement-dependent cytotoxicity (CDC)
.
Clinical trials also showed that the global phase III GALLIUM study showed that octuzumab plus chemotherapy significantly prolonged PFS compared with rituximab plus chemotherapy (5-year PFS rate: 70.
5% vs 63.
2%; p=0.
0043) Patients with treatment-naïve FL had a 34% reduction in the risk of recurrence and death, and a 46% reduction in the risk of early disease progression
.
Currently, octuzumab has been approved by the FDA for the treatment of first-line chronic lymphocytic leukemia (CLL), first-line and relapsed and refractory FL, and its studies in various other indolent lymphomas are also underway, such as mantle cell lymphoma , marginal zone lymphoma, Waldenström's macroglobulinemia, etc.
, expecting to bring more benefits to patients
.
In recent years, many small molecule targeted drugs have been explored in an endless stream.
It is hoped that in the future, patients with indolent lymphoma can achieve long-term disease control without chemotherapy, reduce treatment-related adverse reactions, and allow patients to achieve higher quality and longer survival
.
The emergence of Professor Jin Zhengming's rituximab has not changed the reality that indolent lymphoma cannot be cured.
Therefore, we have changed the treatment goal to prolong the survival of patients, improve the quality of life of patients, and restore patients to a generally normal living state, which also promotes Researchers to explore new treatment options
.
As Professor Wang Li mentioned "no chemotherapy regimen", this is an important direction for indolent lymphoma exploration
.
The chemotherapy-free treatment regimen has achieved great success in FL at this stage.
One of the earliest important regimens to convert this concept into clinical practice is rituximab combined with lenalidomide (R2).
The efficacy is similar to that of immunochemotherapy.
The program is similar.
The biggest advantage of this program is that it avoids chemotherapy and reduces the pain of medication for patients, so that patients who cannot tolerate chemotherapy have new treatment options.
Therefore, the R2 program created the so-called "Chemo-Free" times
.
The study of the novel octuzumab combined with lenalidomide (Glen) in the first-line treatment of FL patients with high tumor burden has also shown good efficacy: 2-year PFS reached 96%, and the overall response rate (ORR) was as high as 98%
.
The emergence of small-molecule drugs such as BTK inhibitors, BCL-2 inhibitors, and PI3K inhibitors has also given patients with indolent lymphoma more options for medication
.
Yimaitong: Anti-CD20 monoclonal antibody has always been the cornerstone drug in the field of indolent lymphoma.
Now the first-line indication of the new oltuzumab has entered medical insurance.
What do you think it means for patients and the field of indolent lymphoma? Professor Jin Zhengming's drug accessibility is the core of its application value.
Reducing the burden on patients and allowing good drugs to enter medical insurance are important measures to improve drug accessibility
.
Ortuzumab, as the world's first type II humanized anti-CD20 monoclonal antibody that has undergone glycosylation, took just over 3 months from its launch at the end of August last year to its entry into the medical insurance list
.
Currently, newly treated FL patients who meet the treatment indications in the clinic usually choose octuzumab combined with chemotherapy, because in the field of FL, octuzumab is the first targeted drug to achieve full coverage of induction and maintenance therapy.
Covering gaps in the coverage of FL maintenance therapy within the catalog
.
Although the indications for octuzumab included in medical insurance are currently narrow, its disease application is generally broad, and it has shown excellent efficacy in a variety of B-cell lymphomas other than FL
.
At present, our department has accumulated a certain amount of experience in the application of ortuzumab.
Its safety during infusion is good, and the adverse reactions are similar to those of rituximab, and no unexpected adverse events have occurred
.
At the same time, we also observed that some patients who had failed rituximab treatment in the past also obtained good efficacy from otuzumab
.
Professor Wang Li has greatly enhanced drug accessibility for patients, and FL patients can receive better and safer drugs
.
Many patients in our department who cannot continue to use rituximab due to severe allergic or infusion reactions can have a good infusion experience after switching to otuzumab without any adverse reactions
.
In FL patients with high tumor burden, octuzumab had higher tumor permeability and significantly improved clearance
.
In the first-line treatment, the combination regimen of octuzumab is used for induction + octuzumab single-agent maintenance, and the patient's recurrence-free progression time is longer.
For the overall survival period, the burden of treatment costs and the risk of recurrence caused by recurrence are greatly reduced.
Anxiety and other psychological problems
.
In short, the emergence of rituximab has brought good news to the majority of lymphoma patients.
As a new generation of anti-CD20 monoclonal antibody, otuzumab has set a new milestone for the first-line treatment of lymphoma
.
Professor Jin Zhengming, Head of Lymphoma Subspecialty, Hematology Department, First Affiliated Hospital of Soochow University, Member of Lymphoma Professional Committee of China Anti-Cancer Association, Member of Lymphoma Group, Hematology Branch of Chinese Medical Association, Vice Chairman of Lymphoma Professional Committee of Jiangsu Cancer Prevention and Control Alliance Jiangsu Province Member of the Standing Committee of the Anti-Cancer Association, Member of the Jiangsu Provincial Blood Disease Quality Management Committee, Member of the Blood Branch of the Chinese Geriatrics Association, and participated in the compilation of [Hematology], [Training Textbooks on the Standardized Use of Antibacterial Drugs by the Ministry of Health], etc.
, in the fields of diagnosis and treatment of malignant hematological diseases and hematopoietic stem cell transplantation With rich clinical experience, Professor Wang Li, Chief Physician, Department of Hematology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine Doctor of Shanghai Jiaotong University School of Medicine, Ph.
D.
Supervisor Youth Member of Hematology Branch Member of Laboratory Diagnostics Group of Chinese Medical Association Young Member of Chinese Aged Hematology Lymphoma Group Chaired 3 National Natural Science Foundation projects, 4 provincial-level projects, and 7 provincial and ministerial-level awards won by Shanghai Municipal Education Commission plateau Gaofeng Talent Shanghai Outstanding Young Medical Talent ★ Scan the QR code below to enter the "Mystery Exploration" channel ★ Click "Read the original text" to enter the "Mystery Exploration" channel!
Although there is no cure for indolent lymphoma at present, looking back over the past three decades, with the continuous emergence of new drugs, the treatment mode of indolent lymphoma has undergone tremendous changes.
The patient's survival has improved significantly
.
Yimaitong specially invited Professor Jin Zhengming from the Department of Hematology of the First Affiliated Hospital of Soochow University and Professor Wang Li of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine for an interview, reviewing the development history of indolent lymphoma, and learning from indolent lymphoma based on the current clinical practice.
The pioneering spirit of hard work, in order to benefit more laziness patients
.
Yi Mai Tong: First of all, please review the treatment mode of indolent lymphoma and the survival status of patients before the advent of rituximab
.
Before the advent of rituximab by Professor Jin Zhengming, the main treatment for indolent lymphoma was chemotherapy, which we call the era of chemotherapy.
From the beginning of single-agent chemotherapy, it gradually developed into multi-drug combination chemotherapy.
Treatment presents many serious challenges
.
The first is chemotherapy-related adverse reactions.
Patients with indolent lymphoma are often older and have poor tolerance to chemotherapy.
Second, whether increasing the dose of chemotherapy or combining chemotherapy drugs, it seems that the survival of patients cannot be significantly improved.
More adverse reactions; in addition, for patients with indolent lymphoma with low tumor burden, aggressive chemotherapy regimens cannot significantly improve patient survival, so "watch and wait" therapy is the preferred treatment for patients with indolent lymphoma.
After the patient develops symptoms, the chemotherapy regimen is formulated according to the individual situation
.
Yi Mai Tong: Rituximab, as a milestone drug in the field of lymphoma, has established an unshakable position in just a few decades
.
How did rituximab revolutionize the treatment paradigm for indolent lymphoma? Professor Wang Li's breakthroughs in indolent lymphoma signal transduction pathways and anti-tumor immune responses, especially in the research of non-cytotoxic drugs, support the development of tumor immunity
.
Rituximab is an epoch-making drug in the treatment of indolent lymphoma
.
The application of rituximab in indolent lymphoma is also a process of gradual exploration, which is mainly divided into two stages
.
Rituximab single-agent induction vs waiting and observation: As Professor Jin Zhengming said, for patients with indolent lymphoma with low tumor burden, the first choice is to wait and observe treatment in the early stage
.
A study in the United Kingdom in asymptomatic and mass-free stage II, III, and IV FL-naïve patients compared watchful waiting with rituximab single-agent induction, rituximab single-agent induction + maintenance Efficacy among the three groups
.
The recent (7-month) remission rate increased significantly from 6% to 74% and 88%, respectively (p<0.
01); the 3-year progression-free survival rate increased significantly from 33% to 60% and 81%, respectively (p<0.
01).
And rituximab treatment also significantly delayed the time to receive chemotherapy or radiation
.
Rituximab combined with chemotherapy vs traditional chemotherapy: In the past, chemotherapy-based treatment of indolent lymphoma has achieved remission, but it is difficult to prolong the overall survival (OS) of patients
.
After the emergence of rituximab, a number of clinical studies have shown that rituximab combined with various chemotherapy regimens (including CVP, CHOP, etc.
) in the first-line treatment of FL have shown long-term survival benefits
.
Three pivotal studies of R in the treatment of FL: GLSG2000, M39021, and M39023, respectively compared the efficacy of chemotherapy combined with targeted therapy and chemotherapy alone in newly treated patients
.
The results showed that the survival rate of patients in the R-chemo (R combined with chemotherapy) group was improved compared with the patients in the chemotherapy alone group, and there was a significant difference in overall survival
.
On this basis, the Eastern Cooperative Oncology Group (ECOG) conducted the ECOG1496 study in treatment-naïve FL patients, revealing that rituximab maintenance therapy can benefit FL patients
.
So far, rituximab-based immunochemotherapy has become the first-line treatment of FL, and we call this period the era of immunochemotherapy
.
Yimaitong: In order to improve the efficacy and drug safety of indolent lymphoma, what other explorations have been made by workers in this field? Professor Wang Li's therapeutic exploration in the field of indolent lymphoma has never stopped
.
In the exploration of chemotherapy drugs, rituximab combined with bendamustine can effectively improve the treatment effect of patients, reduce recurrence, and in terms of adverse reactions, it can significantly reduce myelosuppression and cardiotoxicity compared with the R-CHOP regimen.
.
In terms of monoclonal antibody exploration, in preclinical studies, the type II humanized anti-CD20 monoclonal antibody octuzumab has been shown to have stronger antibody-dependent cell-mediated effects than murine rituximab Cytotoxicity (ADCC) and phagocytosis (ADCP), lower complement-dependent cytotoxicity (CDC)
.
Clinical trials also showed that the global phase III GALLIUM study showed that octuzumab plus chemotherapy significantly prolonged PFS compared with rituximab plus chemotherapy (5-year PFS rate: 70.
5% vs 63.
2%; p=0.
0043) Patients with treatment-naïve FL had a 34% reduction in the risk of recurrence and death, and a 46% reduction in the risk of early disease progression
.
Currently, octuzumab has been approved by the FDA for the treatment of first-line chronic lymphocytic leukemia (CLL), first-line and relapsed and refractory FL, and its studies in various other indolent lymphomas are also underway, such as mantle cell lymphoma , marginal zone lymphoma, Waldenström's macroglobulinemia, etc.
, expecting to bring more benefits to patients
.
In recent years, many small molecule targeted drugs have been explored in an endless stream.
It is hoped that in the future, patients with indolent lymphoma can achieve long-term disease control without chemotherapy, reduce treatment-related adverse reactions, and allow patients to achieve higher quality and longer survival
.
The emergence of Professor Jin Zhengming's rituximab has not changed the reality that indolent lymphoma cannot be cured.
Therefore, we have changed the treatment goal to prolong the survival of patients, improve the quality of life of patients, and restore patients to a generally normal living state, which also promotes Researchers to explore new treatment options
.
As Professor Wang Li mentioned "no chemotherapy regimen", this is an important direction for indolent lymphoma exploration
.
The chemotherapy-free treatment regimen has achieved great success in FL at this stage.
One of the earliest important regimens to convert this concept into clinical practice is rituximab combined with lenalidomide (R2).
The efficacy is similar to that of immunochemotherapy.
The program is similar.
The biggest advantage of this program is that it avoids chemotherapy and reduces the pain of medication for patients, so that patients who cannot tolerate chemotherapy have new treatment options.
Therefore, the R2 program created the so-called "Chemo-Free" times
.
The study of the novel octuzumab combined with lenalidomide (Glen) in the first-line treatment of FL patients with high tumor burden has also shown good efficacy: 2-year PFS reached 96%, and the overall response rate (ORR) was as high as 98%
.
The emergence of small-molecule drugs such as BTK inhibitors, BCL-2 inhibitors, and PI3K inhibitors has also given patients with indolent lymphoma more options for medication
.
Yimaitong: Anti-CD20 monoclonal antibody has always been the cornerstone drug in the field of indolent lymphoma.
Now the first-line indication of the new oltuzumab has entered medical insurance.
What do you think it means for patients and the field of indolent lymphoma? Professor Jin Zhengming's drug accessibility is the core of its application value.
Reducing the burden on patients and allowing good drugs to enter medical insurance are important measures to improve drug accessibility
.
Ortuzumab, as the world's first type II humanized anti-CD20 monoclonal antibody that has undergone glycosylation, took just over 3 months from its launch at the end of August last year to its entry into the medical insurance list
.
Currently, newly treated FL patients who meet the treatment indications in the clinic usually choose octuzumab combined with chemotherapy, because in the field of FL, octuzumab is the first targeted drug to achieve full coverage of induction and maintenance therapy.
Covering gaps in the coverage of FL maintenance therapy within the catalog
.
Although the indications for octuzumab included in medical insurance are currently narrow, its disease application is generally broad, and it has shown excellent efficacy in a variety of B-cell lymphomas other than FL
.
At present, our department has accumulated a certain amount of experience in the application of ortuzumab.
Its safety during infusion is good, and the adverse reactions are similar to those of rituximab, and no unexpected adverse events have occurred
.
At the same time, we also observed that some patients who had failed rituximab treatment in the past also obtained good efficacy from otuzumab
.
Professor Wang Li has greatly enhanced drug accessibility for patients, and FL patients can receive better and safer drugs
.
Many patients in our department who cannot continue to use rituximab due to severe allergic or infusion reactions can have a good infusion experience after switching to otuzumab without any adverse reactions
.
In FL patients with high tumor burden, octuzumab had higher tumor permeability and significantly improved clearance
.
In the first-line treatment, the combination regimen of octuzumab is used for induction + octuzumab single-agent maintenance, and the patient's recurrence-free progression time is longer.
For the overall survival period, the burden of treatment costs and the risk of recurrence caused by recurrence are greatly reduced.
Anxiety and other psychological problems
.
In short, the emergence of rituximab has brought good news to the majority of lymphoma patients.
As a new generation of anti-CD20 monoclonal antibody, otuzumab has set a new milestone for the first-line treatment of lymphoma
.
Professor Jin Zhengming, Head of Lymphoma Subspecialty, Hematology Department, First Affiliated Hospital of Soochow University, Member of Lymphoma Professional Committee of China Anti-Cancer Association, Member of Lymphoma Group, Hematology Branch of Chinese Medical Association, Vice Chairman of Lymphoma Professional Committee of Jiangsu Cancer Prevention and Control Alliance Jiangsu Province Member of the Standing Committee of the Anti-Cancer Association, Member of the Jiangsu Provincial Blood Disease Quality Management Committee, Member of the Blood Branch of the Chinese Geriatrics Association, and participated in the compilation of [Hematology], [Training Textbooks on the Standardized Use of Antibacterial Drugs by the Ministry of Health], etc.
, in the fields of diagnosis and treatment of malignant hematological diseases and hematopoietic stem cell transplantation With rich clinical experience, Professor Wang Li, Chief Physician, Department of Hematology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine Doctor of Shanghai Jiaotong University School of Medicine, Ph.
D.
Supervisor Youth Member of Hematology Branch Member of Laboratory Diagnostics Group of Chinese Medical Association Young Member of Chinese Aged Hematology Lymphoma Group Chaired 3 National Natural Science Foundation projects, 4 provincial-level projects, and 7 provincial and ministerial-level awards won by Shanghai Municipal Education Commission plateau Gaofeng Talent Shanghai Outstanding Young Medical Talent ★ Scan the QR code below to enter the "Mystery Exploration" channel ★ Click "Read the original text" to enter the "Mystery Exploration" channel!
