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Follicular Lymphoma (FL) originates from B lymphocytes in the germinal center and is one of the most common indolent lymphomas
.
At present, the treatment of follicular lymphoma is mainly based on rituximab-based immunochemotherapy, but patients still have unmet need for treatment.
If most FL cannot be cured, patients will have multiple relapses, each time After recurrence, the duration of treatment remission is gradually shortened, and the chance of refractory treatment increases; in addition, some patients have early progression or recurrence, or transformation to aggressive lymphoma, and so on
.
With the rise of molecular targeted drugs and immunotherapy, the prognosis of FL patients has been further improved, and the treatment model of FL has also undergone a revolutionary change, gradually changing from an immunochemotherapy model to a non-chemotherapy model
.
Yimaitong invited Professor Xia Zhongjun from the Department of Hematology Oncology, Sun Yat-sen University Cancer Hospital, and Professor Zhang Liling from the Cancer Center of Union Hospital, Tongji Medical College of Huazhong University of Science and Technology to discuss the current status of FL treatment and its future development
.
Q1: Could you please introduce the current treatment status of follicular lymphoma and what is the treatment dilemma? Prof.
Zhongjun Xia FL is a common subtype of indolent B-cell lymphoma, the disease progresses slowly, and most patients have progressed to stage III~IV when they see a doctor
.
Taking the single-center data of Sun Yat-sen University Cancer Hospital as an example, according to incomplete statistics, there are more than 1,500 cases of lymphoma and more than 300 cases of FL diagnosed each year, of which about 75% of patients are diagnosed with stage III/IV FL
.
These patients often cannot be cured, and disease progression may occur during treatment, leading to treatment failure or death
.
Therefore, the current main treatment goal of FL is to extend the patient’s progression-free survival (PFS), thereby prolonging the patient’s overall survival (OS)
.
In addition, during the entire course of FL, most patients will have multiple recurrences and progress, and the difficulty of treatment will increase after each relapse.
Especially patients with disease progression (POD24) within two years after the start of first-line treatment have significantly poorer OS
.
Studies have shown that about 20%-25% of FL patients will develop POD24, and the 5-year OS rate of this part of patients is only 50%
.
Therefore, POD24 has become an urgent problem in FL treatment
.
Although Professor Zhang Liling currently has prognostic tools such as FLIPI-1, FLIPI-2, and PRIMA-PI, there is no best prognostic model that can accurately predict the occurrence of POD24, and various prognostic tools have certain limitations
.
At this stage, the FL field needs to further explore the bioprognostic markers of high-risk patients, and identify POD24 patients as soon as possible
.
In addition, some FL patients will have a pathological transformation.
About 30%-40% of FL patients will transform into aggressive diffuse large B-cell lymphoma (DLBCL), of which about 21% are "double-hit" DLBCL.
The patient is more difficult to treat and the prognosis is worse
.
How to identify patients with transformation characteristics as early as possible, and how to reduce the risk of transformation in treatment, is also the direction to be explored in the diagnosis and treatment of FL
.
At present, our center is participating in a multi-center retrospective study led by Professor Xu Bing, aiming to explore the correlation between clinical factors and the prognosis of newly-treated FL.
The data is still in the stage of collation.
I hope that the results of the study can help clinicians to be more accurate.
Identify high-risk patients
.
Q2: Based on your many years of clinical experience, can you talk about the evolution of treatment strategies for initial treatment of FL? In recent years, what are the research developments worth paying attention to in the field of FL treatment? Professor Xia Zhongjun Before the advent of CD20 monoclonal antibody, the treatment plan for FL was mainly chemotherapy.
Although it can relieve the disease, it is difficult to prolong the patient's OS
.
After the emergence of rituximab, a number of clinical studies have shown that rituximab combined with various chemotherapy regimens (including CVP, CHOP, etc.
) first-line treatment of FL have shown long-term survival benefits.
So far, rituximab Anti-based immunochemotherapy has become the first-line treatment of FL
.
Subsequently, the researchers explored the optimal chemotherapy regimen in combination with rituximab
.
The most representative is the FOLL 05 study, which compared patients with advanced FL who received R-CVP (rituximab, cyclophosphamide, vincristine, prednisone), R-CHOP and RFM (rituximab).
The efficacy and safety of ciximab, fludarabine, mitoxantrone)
.
Research results show that R-CHOP can significantly prolong PFS in patients than R-CVP, and RFM has the most adverse reactions.
Therefore, R-CHOP has become a common immunochemotherapy regimen for the first-line treatment of FL
.
Subsequently, the StiL study compared the efficacy and safety of BR (bendamustine, rituximab) and R-CHOP regimens in patients with indolent lymphoma (including FL).
The study suggested that compared with R-CHOP Scheme, BR scheme can significantly prolong the PFS of FL patients, and has lower toxicity, but OS has no benefit
.
Professor Zhang Liling, with the continuous emergence of new drugs, the treatment of FL has gradually tended to the "no chemotherapy" treatment mode
.
The RELEVANCE study compared the efficacy of R2 (rituximab, lenalidomide) no chemotherapy regimen and traditional rituximab combined chemotherapy (R-chemo) regimen in newly treated FL patients.
The efficacy of chemotherapy is similar to that of traditional R-Chemo, but there are fewer adverse reactions related to chemotherapy, which may improve the quality of life of FL patients during a longer course of disease
.
At present, the R2 program has been written into the CSCO and ESMO guidelines as one of the first-line treatment options
.
In addition, the emergence of new targeted therapy drugs also has a certain impact on the treatment pattern of FL
.
In terms of initial treatment of FL, a new type of CD20 monoclonal antibody, otuzumab, has been approved in China, combined with chemotherapy, for initial treatment of stage II with huge masses, stage III or IV follicular lymphoma Adult patients, patients who have achieved at least partial remission, are subsequently maintained with otuzumab
.
The results of the global Phase III GALLIUM study showed that compared with the traditional R-chemo, G-chemo reduced the risk of progression, recurrence and death in newly treated FL patients by 34%, and the relative risk of POD24 events was reduced by 46%.
There is no significant difference in safety between the schemes
.
Figure 1 The Chinese subgroup analysis of PFS in the GALLIUM study showed that with a median follow-up of 71.
9 months, the disease progression rate in the G-chemo group was lower (32% vs 51.
5%), and the 5-year PFS rate in the G-chemo group was higher than that in the R-chemo group ( Estimated 5-year PFS: 66.
87% vs.
53.
25%), and the cumulative incidence of POD24 events is lower (16.
0% vs.
21.
2%)
.
G-chemo has become a new choice for the first-line treatment of FL patients in China
.
Figure 2 PFSQ3 of the Chinese subgroup of the GALLIUM study: At present, otuzumab has been approved for marketing in China.
What are your expectations for the future treatment of follicular lymphoma, and what new drugs are worth looking forward to? Professor Zhongjun Xia's current humanized new anti-CD20 monoclonal antibody, Otuzumab, has been approved for marketing in China, and has been used in the treatment of FL patients in many countries before
.
A number of research data published abroad have confirmed that compared with R-chemo, G-chemo has more benefits in the treatment of indolent lymphoma, especially in patients with FL
.
Therefore, whether it is the treatment of initial treatment or the treatment of relapsed and refractory FL, clinicians should pay attention to the progress of G-chemo, so that more FL patients can benefit from it
.
Professor Zhang Liling’s retrospective study has confirmed that compared with chemotherapy alone, the application of rituximab in first-line and maintenance therapy can significantly reduce the risk of histological transformation of FL
.
So does the new CD20 monoclonal antibody otuzumab have a certain value in reducing the risk of follicular lymphoma transformation? The relevant research results are very exciting
.
In addition, in order to improve survival and tolerability, the treatment mode of FL has gradually tended to high-efficiency and low-toxicity "de-chemotherapy" regimen
.
The results of a phase II study of otuzumab combined with lenalidomide (GLen regimen) in the treatment of high tumor burden newly-treated FL showed an encouraging effect, with a complete remission rate of 94% and an estimated 2-year PFS rate of 96%.
And it reduces the risk of POD24, but due to the small number of patients, a larger sample study is needed for further verification
.
On the whole, the future application of otuzumab in FL "no chemotherapy" treatment model may also bring new treatment options for patients
.
Figure 3 Phase II study of PFS in the treatment of relapsed and refractory FL.
There are many new targeted therapies and immunotherapy drugs, such as PI3K inhibitors, EZH2 inhibitors, chimeric antigen receptor T cell (CAR-T) therapy, etc.
Shows good anti-tumor activity
.
In the future, the combination of these new drugs with existing treatment options and the efficacy and safety of the new drugs in newly-treated FL patients deserve further attention from clinicians
.
Professor Xia Zhongjun, Department of Hematology and Oncology, Sun Yat-sen University Cancer Hospital, Chairman of the Palliative and Rehabilitation Professional Committee of Guangdong Anti-Cancer Association, Chairman of the Chemotherapy Professional Committee of Guangzhou Anti-Cancer Association, Chairman of the Guangdong Lymphoma Professional Committee of UCOM Alliance, Deputy of the Hematological Oncology Professional Committee of Guangzhou Medical Association Chairperson of the Standing Committee of the Lymphoma Professional Committee of the Guangdong Anti-Cancer Association Member of the Professional Committee of Cancer Rehabilitation and Palliative Care of the Chinese Anti-Cancer Association Director of the Lymphoma Ward of the Hospital Tumor Center Member of the Lymphoma Professional Committee of the Hubei Anti-Cancer Association Member of the CSCO Anti-Lymphoma Alliance Member of the Lymphoma Professional Committee of the Chinese Anti-Cancer Association Member of the Tumor Translational Medicine Group of the Oncology Branch of the Chinese Medical Association Member of the Standing Committee of the Lymphoma Professional Committee Member of the Lymphoma and Hematology Committee of the Chinese Society of Geriatric Cancer Chairperson ★ Scan the QR code below to enter the "Mystery Exploration" channel ★Poke "Read the original text" and enter the "Mystery Exploration" channel!
.
At present, the treatment of follicular lymphoma is mainly based on rituximab-based immunochemotherapy, but patients still have unmet need for treatment.
If most FL cannot be cured, patients will have multiple relapses, each time After recurrence, the duration of treatment remission is gradually shortened, and the chance of refractory treatment increases; in addition, some patients have early progression or recurrence, or transformation to aggressive lymphoma, and so on
.
With the rise of molecular targeted drugs and immunotherapy, the prognosis of FL patients has been further improved, and the treatment model of FL has also undergone a revolutionary change, gradually changing from an immunochemotherapy model to a non-chemotherapy model
.
Yimaitong invited Professor Xia Zhongjun from the Department of Hematology Oncology, Sun Yat-sen University Cancer Hospital, and Professor Zhang Liling from the Cancer Center of Union Hospital, Tongji Medical College of Huazhong University of Science and Technology to discuss the current status of FL treatment and its future development
.
Q1: Could you please introduce the current treatment status of follicular lymphoma and what is the treatment dilemma? Prof.
Zhongjun Xia FL is a common subtype of indolent B-cell lymphoma, the disease progresses slowly, and most patients have progressed to stage III~IV when they see a doctor
.
Taking the single-center data of Sun Yat-sen University Cancer Hospital as an example, according to incomplete statistics, there are more than 1,500 cases of lymphoma and more than 300 cases of FL diagnosed each year, of which about 75% of patients are diagnosed with stage III/IV FL
.
These patients often cannot be cured, and disease progression may occur during treatment, leading to treatment failure or death
.
Therefore, the current main treatment goal of FL is to extend the patient’s progression-free survival (PFS), thereby prolonging the patient’s overall survival (OS)
.
In addition, during the entire course of FL, most patients will have multiple recurrences and progress, and the difficulty of treatment will increase after each relapse.
Especially patients with disease progression (POD24) within two years after the start of first-line treatment have significantly poorer OS
.
Studies have shown that about 20%-25% of FL patients will develop POD24, and the 5-year OS rate of this part of patients is only 50%
.
Therefore, POD24 has become an urgent problem in FL treatment
.
Although Professor Zhang Liling currently has prognostic tools such as FLIPI-1, FLIPI-2, and PRIMA-PI, there is no best prognostic model that can accurately predict the occurrence of POD24, and various prognostic tools have certain limitations
.
At this stage, the FL field needs to further explore the bioprognostic markers of high-risk patients, and identify POD24 patients as soon as possible
.
In addition, some FL patients will have a pathological transformation.
About 30%-40% of FL patients will transform into aggressive diffuse large B-cell lymphoma (DLBCL), of which about 21% are "double-hit" DLBCL.
The patient is more difficult to treat and the prognosis is worse
.
How to identify patients with transformation characteristics as early as possible, and how to reduce the risk of transformation in treatment, is also the direction to be explored in the diagnosis and treatment of FL
.
At present, our center is participating in a multi-center retrospective study led by Professor Xu Bing, aiming to explore the correlation between clinical factors and the prognosis of newly-treated FL.
The data is still in the stage of collation.
I hope that the results of the study can help clinicians to be more accurate.
Identify high-risk patients
.
Q2: Based on your many years of clinical experience, can you talk about the evolution of treatment strategies for initial treatment of FL? In recent years, what are the research developments worth paying attention to in the field of FL treatment? Professor Xia Zhongjun Before the advent of CD20 monoclonal antibody, the treatment plan for FL was mainly chemotherapy.
Although it can relieve the disease, it is difficult to prolong the patient's OS
.
After the emergence of rituximab, a number of clinical studies have shown that rituximab combined with various chemotherapy regimens (including CVP, CHOP, etc.
) first-line treatment of FL have shown long-term survival benefits.
So far, rituximab Anti-based immunochemotherapy has become the first-line treatment of FL
.
Subsequently, the researchers explored the optimal chemotherapy regimen in combination with rituximab
.
The most representative is the FOLL 05 study, which compared patients with advanced FL who received R-CVP (rituximab, cyclophosphamide, vincristine, prednisone), R-CHOP and RFM (rituximab).
The efficacy and safety of ciximab, fludarabine, mitoxantrone)
.
Research results show that R-CHOP can significantly prolong PFS in patients than R-CVP, and RFM has the most adverse reactions.
Therefore, R-CHOP has become a common immunochemotherapy regimen for the first-line treatment of FL
.
Subsequently, the StiL study compared the efficacy and safety of BR (bendamustine, rituximab) and R-CHOP regimens in patients with indolent lymphoma (including FL).
The study suggested that compared with R-CHOP Scheme, BR scheme can significantly prolong the PFS of FL patients, and has lower toxicity, but OS has no benefit
.
Professor Zhang Liling, with the continuous emergence of new drugs, the treatment of FL has gradually tended to the "no chemotherapy" treatment mode
.
The RELEVANCE study compared the efficacy of R2 (rituximab, lenalidomide) no chemotherapy regimen and traditional rituximab combined chemotherapy (R-chemo) regimen in newly treated FL patients.
The efficacy of chemotherapy is similar to that of traditional R-Chemo, but there are fewer adverse reactions related to chemotherapy, which may improve the quality of life of FL patients during a longer course of disease
.
At present, the R2 program has been written into the CSCO and ESMO guidelines as one of the first-line treatment options
.
In addition, the emergence of new targeted therapy drugs also has a certain impact on the treatment pattern of FL
.
In terms of initial treatment of FL, a new type of CD20 monoclonal antibody, otuzumab, has been approved in China, combined with chemotherapy, for initial treatment of stage II with huge masses, stage III or IV follicular lymphoma Adult patients, patients who have achieved at least partial remission, are subsequently maintained with otuzumab
.
The results of the global Phase III GALLIUM study showed that compared with the traditional R-chemo, G-chemo reduced the risk of progression, recurrence and death in newly treated FL patients by 34%, and the relative risk of POD24 events was reduced by 46%.
There is no significant difference in safety between the schemes
.
Figure 1 The Chinese subgroup analysis of PFS in the GALLIUM study showed that with a median follow-up of 71.
9 months, the disease progression rate in the G-chemo group was lower (32% vs 51.
5%), and the 5-year PFS rate in the G-chemo group was higher than that in the R-chemo group ( Estimated 5-year PFS: 66.
87% vs.
53.
25%), and the cumulative incidence of POD24 events is lower (16.
0% vs.
21.
2%)
.
G-chemo has become a new choice for the first-line treatment of FL patients in China
.
Figure 2 PFSQ3 of the Chinese subgroup of the GALLIUM study: At present, otuzumab has been approved for marketing in China.
What are your expectations for the future treatment of follicular lymphoma, and what new drugs are worth looking forward to? Professor Zhongjun Xia's current humanized new anti-CD20 monoclonal antibody, Otuzumab, has been approved for marketing in China, and has been used in the treatment of FL patients in many countries before
.
A number of research data published abroad have confirmed that compared with R-chemo, G-chemo has more benefits in the treatment of indolent lymphoma, especially in patients with FL
.
Therefore, whether it is the treatment of initial treatment or the treatment of relapsed and refractory FL, clinicians should pay attention to the progress of G-chemo, so that more FL patients can benefit from it
.
Professor Zhang Liling’s retrospective study has confirmed that compared with chemotherapy alone, the application of rituximab in first-line and maintenance therapy can significantly reduce the risk of histological transformation of FL
.
So does the new CD20 monoclonal antibody otuzumab have a certain value in reducing the risk of follicular lymphoma transformation? The relevant research results are very exciting
.
In addition, in order to improve survival and tolerability, the treatment mode of FL has gradually tended to high-efficiency and low-toxicity "de-chemotherapy" regimen
.
The results of a phase II study of otuzumab combined with lenalidomide (GLen regimen) in the treatment of high tumor burden newly-treated FL showed an encouraging effect, with a complete remission rate of 94% and an estimated 2-year PFS rate of 96%.
And it reduces the risk of POD24, but due to the small number of patients, a larger sample study is needed for further verification
.
On the whole, the future application of otuzumab in FL "no chemotherapy" treatment model may also bring new treatment options for patients
.
Figure 3 Phase II study of PFS in the treatment of relapsed and refractory FL.
There are many new targeted therapies and immunotherapy drugs, such as PI3K inhibitors, EZH2 inhibitors, chimeric antigen receptor T cell (CAR-T) therapy, etc.
Shows good anti-tumor activity
.
In the future, the combination of these new drugs with existing treatment options and the efficacy and safety of the new drugs in newly-treated FL patients deserve further attention from clinicians
.
Professor Xia Zhongjun, Department of Hematology and Oncology, Sun Yat-sen University Cancer Hospital, Chairman of the Palliative and Rehabilitation Professional Committee of Guangdong Anti-Cancer Association, Chairman of the Chemotherapy Professional Committee of Guangzhou Anti-Cancer Association, Chairman of the Guangdong Lymphoma Professional Committee of UCOM Alliance, Deputy of the Hematological Oncology Professional Committee of Guangzhou Medical Association Chairperson of the Standing Committee of the Lymphoma Professional Committee of the Guangdong Anti-Cancer Association Member of the Professional Committee of Cancer Rehabilitation and Palliative Care of the Chinese Anti-Cancer Association Director of the Lymphoma Ward of the Hospital Tumor Center Member of the Lymphoma Professional Committee of the Hubei Anti-Cancer Association Member of the CSCO Anti-Lymphoma Alliance Member of the Lymphoma Professional Committee of the Chinese Anti-Cancer Association Member of the Tumor Translational Medicine Group of the Oncology Branch of the Chinese Medical Association Member of the Standing Committee of the Lymphoma Professional Committee Member of the Lymphoma and Hematology Committee of the Chinese Society of Geriatric Cancer Chairperson ★ Scan the QR code below to enter the "Mystery Exploration" channel ★Poke "Read the original text" and enter the "Mystery Exploration" channel!
