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In order to promote academic exchanges and scientific and technological cooperation in the field of clinical oncology in China, and actively promote the development of the discipline, the 24th session is hosted by the Chinese Society of Clinical Oncology (CSCO), Beijing Hisco Clinical Oncology Research Foundation, and the Cancer Hospital of the Chinese Academy of Medical Sciences The National Clinical Oncology Conference and the 2021 CSCO Annual Conference will be held online from September 25th to 29th, 2021
.
With the theme of "Focus on Innovative Research, Leading the Original Future", this year's National Clinical Oncology Conference brought together well-known experts at home and abroad, focused on the clinical frontiers of oncology, and presented a gluttonous academic feast
.
On this occasion, Yimaitong cordially invites Professor Jin Jie from the First Affiliated Hospital of Zhejiang University School of Medicine to accept an interview to share how China’s relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) current status of treatment
.
Professor Jin Jie, Doctor of Medicine, Professor, Chief Physician, Doctoral Supervisor, Director of the Department of Hematology, The First Affiliated Hospital of Zhejiang University School of Medicine, and subject leader, Director of the Lymphoma Center, Zhejiang University First Hospital, Director of the Key Laboratory of Hematological Oncology (Diagnosis and Treatment), Zhejiang University Medical Science, Zhejiang University Director of the Department of Hematology, National Health Commission, Key Clinical Discipline of the National Health Commission-Hematology Discipline Leader, Zhejiang Provincial Key Innovation Team-Leukemia Basic and Clinical Research Innovation Team Leader, Chinese Women Physician Association Hematology Committee Chairman, Chinese Anti-Cancer Association Hematological Transformation Chairman of the Medical Specialized Committee CSCO Anti-leukemia Alliance Vice Chairman, Chinese Medical Doctor Association, Integrative Hematology Society, Vice Chairman, Chinese Medical Doctor Association, Standing Committee of the Hematology Society, Standing Committee of CSCO Anti-Lymphoma Alliance, Standing Committee of the Cross-Strait Hematology Society, Standing Committee, China Health Promotion Association Hematology Branch Committee member Yi Maitong, Chairman of the Hematology Branch of the Zhejiang Medical Association: Could you please talk about the current status of diagnosis and treatment of r/r DLBCL in China and the focus of clinical attention? Professor Jin Jie, DLBCL is the most common type of lymphoma in both European and American countries or Asian countries
.
Currently, clinical treatment of DLBCL usually adopts immunochemotherapy, such as R-CHOP (rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone)
.
Immunochemotherapy can relieve about 70% of patients, and about 50% of patients achieve 5-year progression-free survival1, but there are still some patients who relapse.
This part of patients is the focus of clinicians’ attention and is also the patients most in need of breakthrough in treatment.
Type
.
Yimaitong: In clinical practice, DLBCL is a very heterogeneous disease.
Which subtypes will the current treatment focus on? Professor Jin Jie’s DLBCL is very heterogeneous and contains many subtypes
.
When the detection technology is not mature, DLBCL is divided into GCB type and non-GCB type (such as ABC type) in clinical practice
.
Now through some new detection technologies, such as second-generation sequencing, DLBCL is divided into more subtypes
.
There are also many new targeted drugs.
These targeted drugs may be effective against DLBCL with certain genetic mutations.
DLBCL has gradually entered the era of precision treatment
.
Yimaitong: We have also learned that CAR-T therapy is quite successful in hematological tumors.
As an important cellular immunotherapy, CAR-T therapy has any significance for r/r DLBCL, and it will bring patients What are the benefits? For DLBCL patients, the CAR-T therapy is a new, effective and very promising therapy for DLBCL patients
.
CAR-T cell immunotherapy is a therapy that uses integrated genetically modified T cells to resist tumor cells
.
Chimeric antigen receptors can specifically recognize tumor-related antigen targets, and after recognition and binding, signals that activate proliferating T cells are transmitted to the cell, causing T cell activation and proliferation, thereby effectively killing tumor cells
.
The chemotherapy regimen has treatment limitations.
After chemotherapy, there are still some patients with DLBCL who relapse or are refractory
.
As a new therapy for patients with relapsed/refractory DLBCL, CAR-T therapy is currently the most effective and most promising therapeutic drug product
.
Published research data shows that the effective rates of Akirensai injection and Rekiolense injection (Benoda®) that are currently on the market in China have reached 70%-80%, and the complete remission (CR) rate is both It's about 50%
.
2,3 Yimaitong: You just mentioned the CAR-T products that have been commercialized on the market.
Could you please tell us whether there are differences between them, and what are the differences? Professor Jin Jie’s currently marketed Akirensai injection and Regiorenzai injection (Benoda®) are both the second-generation CAR-T products, and the third and fourth-generation CAR-T products.
It is still in clinical trials
.
The difference between these two CAR-T products is mainly in the costimulatory domain.
The costimulatory domain of Akirensai injection is CD28, and the costimulatory domain of Rekiolense injection is 4-1BB
.
The survival time of 4-1BB CAR-T cells in the body is significantly longer than that of CD28 CAR-T cells, so the effective duration of 4-1BB CAR-T cells will be longer
.
In addition, the results of the RELIANCE clinical study showed that among the 58 evaluable patients treated with Regiorense injection, the best objective response rate (ORR) was 75.
9%; the complete response rate (CR) was 51.
7%; the median Progression-free survival (PFS) and duration of remission (DOR) were 7.
0 months and 8.
0 months, respectively
.
In terms of adverse events, the incidence of cytokine release syndrome (CRS) of grade ≥3 was 5.
1%, and the incidence of neurotoxicity (NT) of grade ≥3 was 3.
4%
.
3 Combining with previous CAR-T research, it can be seen that the two CAR-T products have the same efficacy, while Regiorense Injection (Benoda®) is safer
.
Yimaitong: CAR-T is already the key development direction of immunotherapy in the future.
Please look forward to the future development direction of CAR-T, and how to improve the accessibility of CAR-T in clinical practice to maximize the benefits of patients? Professor Jin Jie moved forward the number of CAR-T treatment lines to improve the efficacy.
In various published studies, CAR-T therapy has shown good efficacy
.
However, because the patients treated with CAR-T are those who have received at least two-line treatment and the treatment has failed, or the autologous hematopoietic stem cell transplantation has failed, its efficacy will be affected to a certain extent
.
For high-risk patients, such as double-strike or triple-strike, double expression, and TP53 mutation patients, the prognosis is poor and easy to relapse.
If CAR-T treatment is moved forward, patients may benefit more
.
4 At present, clinical studies on the advancement of CAR-T treatment are ongoing.
If the results of the study show that its efficacy is better than conventional chemotherapy, after approval of the relevant indications, patients will be able to use CAR-T treatment earlier and obtain better results.
Good efficacy
.
Lower prices and benefit more patients.
The current commercialized CAR-T products are more expensive.
The domestically marketed Akirensai injection is more expensive and has lower patient accessibility
.
Most patients currently using CAR-T treatment are clinical trials.
If CAR-T treatment moves forward in the future to expand the applicable patient population, companies need to make certain adjustments in prices, which will benefit more patients
.
Shorten the preparation time and benefit more.
At present, the preparation of CAR-T cells requires the extraction of patient's T cells for individual preparation, and the preparation time exceeds 2 weeks
.
After CAR-T cells are successfully prepared, they must undergo strict inspections before they can be infused into the patient.
Therefore, after the patient’s T cells are collected, it will take about 20 days before the CAR-T cells can be infused.
.
If the Fast CAR-T or universal CAR-T developed in the future can shorten the waiting time of patients under the premise of ensuring the efficacy, it will bring greater benefits to patients
.
References: [1] Yao Yu, Xia Zuguang, Shen Yang, Wang Ling, Chen Qiusheng, Li Junmin.
Efficacy analysis of R-CHOP regimen in the treatment of patients with diffuse large B-cell lymphoma[J].
International Journal of Blood Transfusion and Hematology, 2008, 31(1):13-17.
[2] Frederick L Locke, Armin Ghobadi, Caron A Jacobson, et al.
Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single -arm, multicentre, phase 1-2 trial.
Lancet Oncol.
2019 January; 20(1): 31–42.
[3] Jun Zhu, Zhitao Ying, Yuqin Song, et al.
Clinical Response of CD19 CAR-T Cells ( relmacabtagene autoleucel, relma-cel)in Adults with Heavily-Pre-Treated Relapsed /Refractory (r/r) Large B-Cell Lymphoma in China.
Blood 2020; 136 (Supplement 1): 39–40.
[4] Sattva S.
Neelapu, Michael Dickinson, Matthew L, et al.
Interim Analysis of ZUMA-12: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) as First-Line Therapy in Patients (Pts) With High-Risk Large B Cell Lymphoma (LBCL ).
Blood 2020; 136 (Supplement 1): 49.
Poke "read the original text", we make progress together
.
With the theme of "Focus on Innovative Research, Leading the Original Future", this year's National Clinical Oncology Conference brought together well-known experts at home and abroad, focused on the clinical frontiers of oncology, and presented a gluttonous academic feast
.
On this occasion, Yimaitong cordially invites Professor Jin Jie from the First Affiliated Hospital of Zhejiang University School of Medicine to accept an interview to share how China’s relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) current status of treatment
.
Professor Jin Jie, Doctor of Medicine, Professor, Chief Physician, Doctoral Supervisor, Director of the Department of Hematology, The First Affiliated Hospital of Zhejiang University School of Medicine, and subject leader, Director of the Lymphoma Center, Zhejiang University First Hospital, Director of the Key Laboratory of Hematological Oncology (Diagnosis and Treatment), Zhejiang University Medical Science, Zhejiang University Director of the Department of Hematology, National Health Commission, Key Clinical Discipline of the National Health Commission-Hematology Discipline Leader, Zhejiang Provincial Key Innovation Team-Leukemia Basic and Clinical Research Innovation Team Leader, Chinese Women Physician Association Hematology Committee Chairman, Chinese Anti-Cancer Association Hematological Transformation Chairman of the Medical Specialized Committee CSCO Anti-leukemia Alliance Vice Chairman, Chinese Medical Doctor Association, Integrative Hematology Society, Vice Chairman, Chinese Medical Doctor Association, Standing Committee of the Hematology Society, Standing Committee of CSCO Anti-Lymphoma Alliance, Standing Committee of the Cross-Strait Hematology Society, Standing Committee, China Health Promotion Association Hematology Branch Committee member Yi Maitong, Chairman of the Hematology Branch of the Zhejiang Medical Association: Could you please talk about the current status of diagnosis and treatment of r/r DLBCL in China and the focus of clinical attention? Professor Jin Jie, DLBCL is the most common type of lymphoma in both European and American countries or Asian countries
.
Currently, clinical treatment of DLBCL usually adopts immunochemotherapy, such as R-CHOP (rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone)
.
Immunochemotherapy can relieve about 70% of patients, and about 50% of patients achieve 5-year progression-free survival1, but there are still some patients who relapse.
This part of patients is the focus of clinicians’ attention and is also the patients most in need of breakthrough in treatment.
Type
.
Yimaitong: In clinical practice, DLBCL is a very heterogeneous disease.
Which subtypes will the current treatment focus on? Professor Jin Jie’s DLBCL is very heterogeneous and contains many subtypes
.
When the detection technology is not mature, DLBCL is divided into GCB type and non-GCB type (such as ABC type) in clinical practice
.
Now through some new detection technologies, such as second-generation sequencing, DLBCL is divided into more subtypes
.
There are also many new targeted drugs.
These targeted drugs may be effective against DLBCL with certain genetic mutations.
DLBCL has gradually entered the era of precision treatment
.
Yimaitong: We have also learned that CAR-T therapy is quite successful in hematological tumors.
As an important cellular immunotherapy, CAR-T therapy has any significance for r/r DLBCL, and it will bring patients What are the benefits? For DLBCL patients, the CAR-T therapy is a new, effective and very promising therapy for DLBCL patients
.
CAR-T cell immunotherapy is a therapy that uses integrated genetically modified T cells to resist tumor cells
.
Chimeric antigen receptors can specifically recognize tumor-related antigen targets, and after recognition and binding, signals that activate proliferating T cells are transmitted to the cell, causing T cell activation and proliferation, thereby effectively killing tumor cells
.
The chemotherapy regimen has treatment limitations.
After chemotherapy, there are still some patients with DLBCL who relapse or are refractory
.
As a new therapy for patients with relapsed/refractory DLBCL, CAR-T therapy is currently the most effective and most promising therapeutic drug product
.
Published research data shows that the effective rates of Akirensai injection and Rekiolense injection (Benoda®) that are currently on the market in China have reached 70%-80%, and the complete remission (CR) rate is both It's about 50%
.
2,3 Yimaitong: You just mentioned the CAR-T products that have been commercialized on the market.
Could you please tell us whether there are differences between them, and what are the differences? Professor Jin Jie’s currently marketed Akirensai injection and Regiorenzai injection (Benoda®) are both the second-generation CAR-T products, and the third and fourth-generation CAR-T products.
It is still in clinical trials
.
The difference between these two CAR-T products is mainly in the costimulatory domain.
The costimulatory domain of Akirensai injection is CD28, and the costimulatory domain of Rekiolense injection is 4-1BB
.
The survival time of 4-1BB CAR-T cells in the body is significantly longer than that of CD28 CAR-T cells, so the effective duration of 4-1BB CAR-T cells will be longer
.
In addition, the results of the RELIANCE clinical study showed that among the 58 evaluable patients treated with Regiorense injection, the best objective response rate (ORR) was 75.
9%; the complete response rate (CR) was 51.
7%; the median Progression-free survival (PFS) and duration of remission (DOR) were 7.
0 months and 8.
0 months, respectively
.
In terms of adverse events, the incidence of cytokine release syndrome (CRS) of grade ≥3 was 5.
1%, and the incidence of neurotoxicity (NT) of grade ≥3 was 3.
4%
.
3 Combining with previous CAR-T research, it can be seen that the two CAR-T products have the same efficacy, while Regiorense Injection (Benoda®) is safer
.
Yimaitong: CAR-T is already the key development direction of immunotherapy in the future.
Please look forward to the future development direction of CAR-T, and how to improve the accessibility of CAR-T in clinical practice to maximize the benefits of patients? Professor Jin Jie moved forward the number of CAR-T treatment lines to improve the efficacy.
In various published studies, CAR-T therapy has shown good efficacy
.
However, because the patients treated with CAR-T are those who have received at least two-line treatment and the treatment has failed, or the autologous hematopoietic stem cell transplantation has failed, its efficacy will be affected to a certain extent
.
For high-risk patients, such as double-strike or triple-strike, double expression, and TP53 mutation patients, the prognosis is poor and easy to relapse.
If CAR-T treatment is moved forward, patients may benefit more
.
4 At present, clinical studies on the advancement of CAR-T treatment are ongoing.
If the results of the study show that its efficacy is better than conventional chemotherapy, after approval of the relevant indications, patients will be able to use CAR-T treatment earlier and obtain better results.
Good efficacy
.
Lower prices and benefit more patients.
The current commercialized CAR-T products are more expensive.
The domestically marketed Akirensai injection is more expensive and has lower patient accessibility
.
Most patients currently using CAR-T treatment are clinical trials.
If CAR-T treatment moves forward in the future to expand the applicable patient population, companies need to make certain adjustments in prices, which will benefit more patients
.
Shorten the preparation time and benefit more.
At present, the preparation of CAR-T cells requires the extraction of patient's T cells for individual preparation, and the preparation time exceeds 2 weeks
.
After CAR-T cells are successfully prepared, they must undergo strict inspections before they can be infused into the patient.
Therefore, after the patient’s T cells are collected, it will take about 20 days before the CAR-T cells can be infused.
.
If the Fast CAR-T or universal CAR-T developed in the future can shorten the waiting time of patients under the premise of ensuring the efficacy, it will bring greater benefits to patients
.
References: [1] Yao Yu, Xia Zuguang, Shen Yang, Wang Ling, Chen Qiusheng, Li Junmin.
Efficacy analysis of R-CHOP regimen in the treatment of patients with diffuse large B-cell lymphoma[J].
International Journal of Blood Transfusion and Hematology, 2008, 31(1):13-17.
[2] Frederick L Locke, Armin Ghobadi, Caron A Jacobson, et al.
Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single -arm, multicentre, phase 1-2 trial.
Lancet Oncol.
2019 January; 20(1): 31–42.
[3] Jun Zhu, Zhitao Ying, Yuqin Song, et al.
Clinical Response of CD19 CAR-T Cells ( relmacabtagene autoleucel, relma-cel)in Adults with Heavily-Pre-Treated Relapsed /Refractory (r/r) Large B-Cell Lymphoma in China.
Blood 2020; 136 (Supplement 1): 39–40.
[4] Sattva S.
Neelapu, Michael Dickinson, Matthew L, et al.
Interim Analysis of ZUMA-12: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) as First-Line Therapy in Patients (Pts) With High-Risk Large B Cell Lymphoma (LBCL ).
Blood 2020; 136 (Supplement 1): 49.
Poke "read the original text", we make progress together
