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Mantle cell lymphoma is a highly heterogeneous type of lymphoma, which is mainly divided into three subtypes: classic mantle cell lymphoma, leukemia-like non-lymphatic mantle cell lymphoma and in situ mantle cell neoplasia.
On April 16-18, 2021, the First National Lymphocytic Disease Academic Conference of the Chinese Medical Association and the 2021 International Lymphoma Update Symposium were successfully held in Chengdu.
The conference invited well-known experts at home and abroad to give wonderful speeches on topics related to lymphocytic diseases.
.
On this occasion, Yimaitong invited Professor Yi Shuhua from the Hospital of Hematology of the Chinese Academy of Medical Sciences to give an interview to share the research progress of mantle cell lymphoma.
Yimaitong: The prognosis of mantle cell lymphoma is poor.
Relapse and refractory is a difficult problem in the treatment of mantle cell lymphoma.
Could you please tell us about the current research developments for relapsed and refractory mantle cell lymphoma, especially for resistant mantle cell lymphoma after first-line treatment? Professor Yi Shuhua mantle cell lymphoma is a rare subtype of lymphoma that mainly occurs in middle-aged and elderly people, and has both indolence and aggressive characteristics.
Its first-line treatment is mainly bridging by induction therapy containing high-dose cytarabine Autologous hematopoietic stem cell transplantation and maintenance therapy with rituximab after transplantation.
Of course, for patients who are not suitable for transplantation, a weaker immunochemotherapy regimen can be selected for induction therapy, such as bendamustine combined with rituximab, etc.
, and maintenance therapy can be determined according to the choice of first-line induction therapy.
Mantle cell lymphoma is incurable, and patients will eventually progress to the disease.
Relapsed and refractory patients have greatly reduced drug sensitivity to common chemotherapy regimens, resulting in very poor efficacy of second-line treatment.
Therefore, the treatment of relapsed and refractory patients is very dependent on the development of new drugs.
The new drugs currently used for mantle cell lymphoma mainly include BTK inhibitors, BCL-2 inhibitors, immunomodulators lenalidomide, and chimeric antigen receptor T cells (CAR-T).
Among them, CAR-T therapy can be described as a revolutionary treatment for relapsed and refractory mantle cell lymphoma.
Its treatment remission rate is very high, with a complete remission rate as high as 60%-70%, and some patients can obtain sustained remission.
However, patients with relapsed and refractory mantle cell lymphoma are often accompanied by highly aggressive molecular biological features, such as abnormal TP53.
The results of many current clinical studies suggest that high-dose cytarabine-based chemotherapy in the first-line treatment does not bring survival benefits to patients with abnormal TP53, and the median overall survival after autologous hematopoietic stem cell transplantation consolidation therapy is only About 2 years.
In addition, clinical research results show that neither BTK inhibitors nor BCL-2 inhibitors can improve the survival of patients with abnormal TP53.
Fortunately, from the current research data, lenalidomide may be able to partially improve the curative effect of mantle cell lymphoma with high-risk cytogenetic abnormalities; CAR-T therapy is currently the only confirmed treatment for TP53 abnormal mantle cell lymphoma.
An effective new treatment for tumor patients, but its long-term efficacy has not been reported so far.
Generally speaking, the pathogenesis of mantle cell lymphoma is very complicated.
For example, patients with abnormal TP53 have very unstable chromosomes, often accompanied by more complex abnormal karyotypes.
Therefore, we cannot expect to overcome the problem of resistance with only one or two drugs.
We hope to design a more comprehensive treatment plan that takes into account all abnormal signaling pathways, so that it is possible to overcome drug resistance.
From the current clinical studies, the application of lenalidomide and CAR-T is a good research direction, but whether it can improve the survival of patients with high-risk and adverse prognostic factors remains to be further studied and explored.
Yimaitong: At present, relevant research is focusing on the establishment of a prognostic model of mantle cell lymphoma.
The prognostic factors of mantle cell lymphoma are also summarized at the 2020 ASH Conference. Could you please introduce the significance of the establishment of a prognostic model for the diagnosis and treatment of mantle cell lymphoma? Professor Yi Shuhua currently has two scoring systems for mantle cell lymphoma prognosis, one is the simple mantle cell lymphoma international prognostic scoring system (MIPI), and the other is the proliferation index of ki-67 (the positive standard is> 30%) The MIPI-C scoring system for risk stratification in conjunction with MIPI.
Mantle cell lymphoma is a subtype of lymphoma characterized by cell proliferation disorders, so the cell proliferation index is of great significance for prognostic evaluation.
Therefore, the ki-67 proliferation index is very important.
In addition, there are relatively few studies on the prognosis assessment model of mantle cell lymphoma.
In 2020, the French team established a so-called genomics prognostic scoring system that combines KMT2D and TP53 gene mutations or deletions on the basis of MIPI-C scores, but the prognostic model only includes 2 molecular biological indicators, which is not true Significant molecular prognostic model.
What is the real molecular prognostic model? The true molecular prognostic model should incorporate the molecular genetic characteristics of the disease as a whole with clinical prognostic relevance, and can guide the patient's choice of medication, which is the ideal molecular prognostic model.
The Hematology Hospital of the Chinese Academy of Medical Sciences also published the results of an exploratory study on the prognostic model of mantle cell lymphoma in 2020 on ASH.
This study is the first to conduct an integrated analysis of the genomics and transcriptomics of 134 patients with mantle cell lymphoma.
According to genetic characteristics, mantle cell lymphoma is divided into four molecular subtypes, C1, C2, C3, and C4.
Each subtype has a different gene expression profile and clinical characteristics.
Importantly, patients of these four molecular subtypes show significant prognostic differences.
The median progression-free survival (PFS) has not been reached in the C1 subtype, 41.
2 months for the C2 subtype, and 30.
7 for the C3 subtype.
Months, 16.
1 months in the C4 subtype (p<0.
001).
We hope that this molecular prognostic model can guide future treatment options.
Yimaitong: What are your expectations for the use of many new drugs and new therapies such as CAR-T therapy in mantle cell lymphoma? Regarding the future treatment prospects of mantle cell lymphoma, what are your prospects? Professor Yi Shuhua’s mantle cell lymphoma is often accompanied by very complex molecular genetic changes after recurrence, including changes in the tumor microenvironment.
Although the application of new therapies such as CAR-T has achieved good results, we cannot expect This problem can be completely overcome by only this kind of therapy.
Therefore, in the future, we will explore more treatment models, such as small molecule targeted drugs combined with cellular immunotherapy, etc.
, hoping to further improve the efficacy of patients with relapsed and refractory mantle cell lymphoma.
In recent years, sequencing and gene expression studies of patients with BTK inhibitor resistance and BCL-2 resistance have shown that abnormal metabolic pathways are an important mechanism leading to resistance.
Inhibitors targeting abnormal metabolic pathways, such as CDK inhibitors, may be able to overcome or avoid the problem of drug resistance in patients.
However, CDK inhibitors have not been well clinically applied in mantle cell lymphoma.
Therefore, new targeted drugs combined with CDK inhibitors may be one of the directions that need to be explored in the field of mantle cell lymphoma in the future, and may be able to improve the survival of patients with relapsed and refractory mantle cell lymphoma.
Professor Yi Shuhua Doctor of Medicine, Associate Chief Physician, Master's Tutor, Hematology Hospital of Chinese Academy of Medical Sciences (Institute of Hematology), National Clinical Research Center for Hematological Diseases, The 11th Committee of Lymphocytic Disease Group of Chinese Medical Association Hematology Branch Member, Youth Committee, Hematology Oncology Committee of China Anti-Cancer Association, Secretary-General, Committee of Hematology and Immunity Branch of Chinese Society of Immunology, Member of Lymphoma Professional Committee of Tianjin Anti-Cancer Association, Member of Tianjin Anti-Aging Association, Youth Member of Professional Committee of Tianjin Integrative Medicine Association Visiting scholar at MD Anderson Cancer Center, United States Postdoctoral fellow at City of Hope National Medical Center, United States stamped "read the original text", we make progress together
On April 16-18, 2021, the First National Lymphocytic Disease Academic Conference of the Chinese Medical Association and the 2021 International Lymphoma Update Symposium were successfully held in Chengdu.
The conference invited well-known experts at home and abroad to give wonderful speeches on topics related to lymphocytic diseases.
.
On this occasion, Yimaitong invited Professor Yi Shuhua from the Hospital of Hematology of the Chinese Academy of Medical Sciences to give an interview to share the research progress of mantle cell lymphoma.
Yimaitong: The prognosis of mantle cell lymphoma is poor.
Relapse and refractory is a difficult problem in the treatment of mantle cell lymphoma.
Could you please tell us about the current research developments for relapsed and refractory mantle cell lymphoma, especially for resistant mantle cell lymphoma after first-line treatment? Professor Yi Shuhua mantle cell lymphoma is a rare subtype of lymphoma that mainly occurs in middle-aged and elderly people, and has both indolence and aggressive characteristics.
Its first-line treatment is mainly bridging by induction therapy containing high-dose cytarabine Autologous hematopoietic stem cell transplantation and maintenance therapy with rituximab after transplantation.
Of course, for patients who are not suitable for transplantation, a weaker immunochemotherapy regimen can be selected for induction therapy, such as bendamustine combined with rituximab, etc.
, and maintenance therapy can be determined according to the choice of first-line induction therapy.
Mantle cell lymphoma is incurable, and patients will eventually progress to the disease.
Relapsed and refractory patients have greatly reduced drug sensitivity to common chemotherapy regimens, resulting in very poor efficacy of second-line treatment.
Therefore, the treatment of relapsed and refractory patients is very dependent on the development of new drugs.
The new drugs currently used for mantle cell lymphoma mainly include BTK inhibitors, BCL-2 inhibitors, immunomodulators lenalidomide, and chimeric antigen receptor T cells (CAR-T).
Among them, CAR-T therapy can be described as a revolutionary treatment for relapsed and refractory mantle cell lymphoma.
Its treatment remission rate is very high, with a complete remission rate as high as 60%-70%, and some patients can obtain sustained remission.
However, patients with relapsed and refractory mantle cell lymphoma are often accompanied by highly aggressive molecular biological features, such as abnormal TP53.
The results of many current clinical studies suggest that high-dose cytarabine-based chemotherapy in the first-line treatment does not bring survival benefits to patients with abnormal TP53, and the median overall survival after autologous hematopoietic stem cell transplantation consolidation therapy is only About 2 years.
In addition, clinical research results show that neither BTK inhibitors nor BCL-2 inhibitors can improve the survival of patients with abnormal TP53.
Fortunately, from the current research data, lenalidomide may be able to partially improve the curative effect of mantle cell lymphoma with high-risk cytogenetic abnormalities; CAR-T therapy is currently the only confirmed treatment for TP53 abnormal mantle cell lymphoma.
An effective new treatment for tumor patients, but its long-term efficacy has not been reported so far.
Generally speaking, the pathogenesis of mantle cell lymphoma is very complicated.
For example, patients with abnormal TP53 have very unstable chromosomes, often accompanied by more complex abnormal karyotypes.
Therefore, we cannot expect to overcome the problem of resistance with only one or two drugs.
We hope to design a more comprehensive treatment plan that takes into account all abnormal signaling pathways, so that it is possible to overcome drug resistance.
From the current clinical studies, the application of lenalidomide and CAR-T is a good research direction, but whether it can improve the survival of patients with high-risk and adverse prognostic factors remains to be further studied and explored.
Yimaitong: At present, relevant research is focusing on the establishment of a prognostic model of mantle cell lymphoma.
The prognostic factors of mantle cell lymphoma are also summarized at the 2020 ASH Conference. Could you please introduce the significance of the establishment of a prognostic model for the diagnosis and treatment of mantle cell lymphoma? Professor Yi Shuhua currently has two scoring systems for mantle cell lymphoma prognosis, one is the simple mantle cell lymphoma international prognostic scoring system (MIPI), and the other is the proliferation index of ki-67 (the positive standard is> 30%) The MIPI-C scoring system for risk stratification in conjunction with MIPI.
Mantle cell lymphoma is a subtype of lymphoma characterized by cell proliferation disorders, so the cell proliferation index is of great significance for prognostic evaluation.
Therefore, the ki-67 proliferation index is very important.
In addition, there are relatively few studies on the prognosis assessment model of mantle cell lymphoma.
In 2020, the French team established a so-called genomics prognostic scoring system that combines KMT2D and TP53 gene mutations or deletions on the basis of MIPI-C scores, but the prognostic model only includes 2 molecular biological indicators, which is not true Significant molecular prognostic model.
What is the real molecular prognostic model? The true molecular prognostic model should incorporate the molecular genetic characteristics of the disease as a whole with clinical prognostic relevance, and can guide the patient's choice of medication, which is the ideal molecular prognostic model.
The Hematology Hospital of the Chinese Academy of Medical Sciences also published the results of an exploratory study on the prognostic model of mantle cell lymphoma in 2020 on ASH.
This study is the first to conduct an integrated analysis of the genomics and transcriptomics of 134 patients with mantle cell lymphoma.
According to genetic characteristics, mantle cell lymphoma is divided into four molecular subtypes, C1, C2, C3, and C4.
Each subtype has a different gene expression profile and clinical characteristics.
Importantly, patients of these four molecular subtypes show significant prognostic differences.
The median progression-free survival (PFS) has not been reached in the C1 subtype, 41.
2 months for the C2 subtype, and 30.
7 for the C3 subtype.
Months, 16.
1 months in the C4 subtype (p<0.
001).
We hope that this molecular prognostic model can guide future treatment options.
Yimaitong: What are your expectations for the use of many new drugs and new therapies such as CAR-T therapy in mantle cell lymphoma? Regarding the future treatment prospects of mantle cell lymphoma, what are your prospects? Professor Yi Shuhua’s mantle cell lymphoma is often accompanied by very complex molecular genetic changes after recurrence, including changes in the tumor microenvironment.
Although the application of new therapies such as CAR-T has achieved good results, we cannot expect This problem can be completely overcome by only this kind of therapy.
Therefore, in the future, we will explore more treatment models, such as small molecule targeted drugs combined with cellular immunotherapy, etc.
, hoping to further improve the efficacy of patients with relapsed and refractory mantle cell lymphoma.
In recent years, sequencing and gene expression studies of patients with BTK inhibitor resistance and BCL-2 resistance have shown that abnormal metabolic pathways are an important mechanism leading to resistance.
Inhibitors targeting abnormal metabolic pathways, such as CDK inhibitors, may be able to overcome or avoid the problem of drug resistance in patients.
However, CDK inhibitors have not been well clinically applied in mantle cell lymphoma.
Therefore, new targeted drugs combined with CDK inhibitors may be one of the directions that need to be explored in the field of mantle cell lymphoma in the future, and may be able to improve the survival of patients with relapsed and refractory mantle cell lymphoma.
Professor Yi Shuhua Doctor of Medicine, Associate Chief Physician, Master's Tutor, Hematology Hospital of Chinese Academy of Medical Sciences (Institute of Hematology), National Clinical Research Center for Hematological Diseases, The 11th Committee of Lymphocytic Disease Group of Chinese Medical Association Hematology Branch Member, Youth Committee, Hematology Oncology Committee of China Anti-Cancer Association, Secretary-General, Committee of Hematology and Immunity Branch of Chinese Society of Immunology, Member of Lymphoma Professional Committee of Tianjin Anti-Cancer Association, Member of Tianjin Anti-Aging Association, Youth Member of Professional Committee of Tianjin Integrative Medicine Association Visiting scholar at MD Anderson Cancer Center, United States Postdoctoral fellow at City of Hope National Medical Center, United States stamped "read the original text", we make progress together
