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Systemic light chain (AL) amyloidosis is a clinical syndrome in which a large number of immunoglobulin light chains are deposited in various organs in the body in the form of amyloid fibers, resulting in the gradual failure of the function of the affected organs
.
Daretuzumab is the world's first fully human monoclonal antibody targeting CD38.
In October 2021, the subcutaneous preparation of Daretuzumab was officially approved by the National Medical Products Administration, becoming the first approved treatment for AL Drugs for type amyloidosis have brought more treatment options for patients
.
Recently, the team of Professor Lu Jin from the Institute of Hematology, Peking University People's Hospital published the latest research results in the Journal of Clinical And Translational Medicine, revealing for the first time the dynamic profile of T cells before and after the treatment of AL amyloidosis with daratumumab
.
Yimaitong invited Professor Lu Jin to accept an interview to share the latest research progress of daratumumab
.
Yimaitong: Recently, your team published an article on T cell changes in the tumor microenvironment of patients with AL amyloidosis before and after the use of daratumumab in the journal Clinical And Translational Medicine
.
Can you first introduce the main results and highlights of this research? And your prospects for future research directions? This study performed single-cell RNA sequencing of T cells before and after treatment with daratumomab combined with cyclophosphamide, bortezomib and dexamethasone in patients with newly diagnosed AL amyloidosis, and analyzed the characteristics of T cell transcriptome Change
.
The study observed a rapid increase in CD8-positive T cells, an increase in type I interferon and cytokines, and a decrease in resident T cell inhibitory molecules after treatment with daratumumab
.
This study revealed for the first time the T cell lineage changes in patients with amyloidosis after treatment with CD38 monoclonal antibody
.
In addition, the results of the study showed that the T cell lineage changes in bone marrow and peripheral blood were basically the same
.
Peripheral blood collection for single-cell sequencing is less traumatic than bone marrow aspiration, and provides a less invasive method for monitoring the transcription characteristics of T cell changes in AL amyloidosis patients
.
The highlights of this study are the first in-depth study of the T cell lineage of patients with AL amyloidosis through single-cell sequencing; the second is the comparison of T cells in patients with AL amyloidosis and myeloma patients after using CD38 monoclonal antibody.
Change
.
The future research directions of AL amyloidosis include: the use of immunomodulators in AL amyloidosis, and the further exploration of the use of daratumumab, so as to further improve the efficacy and reduce toxic side effects and so on
.
Yimaitong: As the main investigator of the daratumomab international multi-center clinical study ANDROMEDA Phase III in China, would you please talk about the main findings of this study? The ANDROMEDA study is an open-label, randomized controlled phase III clinical trial that evaluates the efficacy and safety of daratumumab combined with bortezomib, cyclophosphamide and dexamethasone (D-VCd) regimen compared to VCd regimen
.
A total of 388 patients with newly diagnosed AL amyloidosis were included in the study, and they were randomly enrolled in the group at a ratio of 1:1
.
The just-concluded ASH conference reported on the 18-month milestone data analysis of the ANDROMEDA research
.
The primary endpoint of the study was the hematological response rate.
The complete response rate (CR) of the D-VCd group and VCd group were 59.
5% and 19.
2%, respectively
.
In addition to the hematological remission rate, the organ remission rate is also an important efficacy evaluation index
.
At the 6-month follow-up, the cardiac remission rate of the D-VCd group was 42% and the renal remission rate was 54%; the updated 18-month follow-up results showed that the D-VCd group had a cardiac remission rate of 53% and renal remission.
The rate is 58%
.
Among them, the cardiac remission rate increased significantly with the extension of the treatment time
.
(As shown in Figure 1) Figure 1.
ANDROMEDA Phase III study D-VCd group and VCd group efficacy evaluation ANDROMEDA Phase III clinical trial results show that daratumumab in the first-line treatment of newly diagnosed AL amyloidosis Excellent efficacy
.
With the extension of the study follow-up time, the proportion of patients with organ remission has increased significantly, especially for patients who have achieved deep hematological remission, the chance of organ remission may be higher
.
In addition, the study uses the CR rate of hematology as the primary endpoint of efficacy evaluation.
Compared with previous studies, it is easier to obtain progression-free survival (PFS) or overall response rate (ORR) as an indicator of efficacy evaluation, and it is also easier to evaluate early efficacy.
More precise
.
Yimaitong: Recently, as the corresponding author, you published a domestic multicenter retrospective study of daratumumab in patients with AL amyloidosis in the Chinese Journal of Internal Medicine
.
For Chinese patients with AL amyloidosis, what is the efficacy and safety of daratumumab? For the newly diagnosed AL amyloidosis patients included in the study, daratumomab has a significant effect, and the proportion of patients achieving ≥VGPR is 100%
.
Among patients with relapsed and refractory AL amyloidosis, 85.
7% (12/14) of the patients can achieve the effect of ≥VGPR
.
Patients with AL amyloidosis are usually in poor physical condition.
When they are treated with monoclonal antibodies, they may cause adverse events such as heart failure due to infusion reactions or excessive fluid infusion
.
During the treatment with daratumumab, no infusion reaction above grade 3 occurred, adverse reactions can be controlled, and the safety is good
.
Yimaitong: Could you please talk about the recently approved subcutaneous (SC) dosage form of daratumumab, compared with the intravenous (IV) dosage form, what are the differences in the clinical application of AL amyloidosis? The approval of the SC dosage form of daratumumab is mainly based on the phase III COLUMBA (MMY3012) study.
The ANDROMEDA phase III clinical trial also confirmed the efficacy and safety of the SC dosage form of daratumumab
.
In terms of efficacy, the SC dosage form of daratumomab is basically the same as the IV dosage form
.
In terms of safety, the incidence of infusion-related adverse reactions of the SC dosage form of darretuzumab is lower than that of the IV dosage form of daretuzumab, which is about 9%
.
In addition, the SC dosage form of daratumumab is characterized by a significant reduction in the amount of liquid infusion, and it can be quickly absorbed by the body after injection
.
Due to the high proportion of patients with AL amyloidosis complicated by heart disease and kidney disease, patients often have severe edema, and the requirements for fluid infusion are very high
.
The SC dosage form of daratumumab is the biggest benefit for these patients in clinical application
.
Summary The changes of T cell lineage before and after treatment with daratumumab in patients with AL amyloidosis have been revealed for the first time, and the relevant mechanism of action of daratumumab in the treatment of AL amyloidosis has been further elucidated
.
The latest results of ANDROMEDA's phase III clinical trial show the efficacy of daratumumab in the first-line treatment of newly diagnosed AL amyloidosis
.
Domestic multi-center retrospective studies have further verified the efficacy and safety of daratumumab in Chinese patients
.
Recently, the subcutaneous dosage form of daratumumab has been officially approved, and it is expected that it can bring clinical benefits to more Chinese patients with AL amyloidosis! Associate Professor Lu Jin, Chief Physician, Associate Professor, and Doctoral Supervisor Peking University People’s Hospital, Peking University Institute of Hematology, mainly for multiple myeloma, primary systemic amyloidosis, lymphoma, cellular immunotherapy, etc.
clinical and laboratory Research on the Director-General and Standing Committee Member of the Hematologists Branch of the Chinese Medical Doctor Association, and the Chairman of the Hematology Branch of the Beijing Medical Doctors Association, Deputy Chairman of the Multiple Myeloma Professional Committee of the Chinese Medical Doctor Association and Deputy Chairman of the Professional Committee of Tissue Cell Diseases, Deputy Director of the Hematology Branch of the Chinese Geriatrics Association Chairman and Chairman of the Multiple Myeloma Academic Committee, Deputy Leader of the Plasma Cytology Group of the Hematology Branch of the Chinese Medical Association Member of the China and International Primary Systemic Amyloidosis Collaboration Group International Myeloma Working Group, Asia Pacific Myeloma Working Group Member International The member of the Kidney and Monoclonal Immunoglobulin Disease Research Group stamped "read the original text" and we make progress together
.
Daretuzumab is the world's first fully human monoclonal antibody targeting CD38.
In October 2021, the subcutaneous preparation of Daretuzumab was officially approved by the National Medical Products Administration, becoming the first approved treatment for AL Drugs for type amyloidosis have brought more treatment options for patients
.
Recently, the team of Professor Lu Jin from the Institute of Hematology, Peking University People's Hospital published the latest research results in the Journal of Clinical And Translational Medicine, revealing for the first time the dynamic profile of T cells before and after the treatment of AL amyloidosis with daratumumab
.
Yimaitong invited Professor Lu Jin to accept an interview to share the latest research progress of daratumumab
.
Yimaitong: Recently, your team published an article on T cell changes in the tumor microenvironment of patients with AL amyloidosis before and after the use of daratumumab in the journal Clinical And Translational Medicine
.
Can you first introduce the main results and highlights of this research? And your prospects for future research directions? This study performed single-cell RNA sequencing of T cells before and after treatment with daratumomab combined with cyclophosphamide, bortezomib and dexamethasone in patients with newly diagnosed AL amyloidosis, and analyzed the characteristics of T cell transcriptome Change
.
The study observed a rapid increase in CD8-positive T cells, an increase in type I interferon and cytokines, and a decrease in resident T cell inhibitory molecules after treatment with daratumumab
.
This study revealed for the first time the T cell lineage changes in patients with amyloidosis after treatment with CD38 monoclonal antibody
.
In addition, the results of the study showed that the T cell lineage changes in bone marrow and peripheral blood were basically the same
.
Peripheral blood collection for single-cell sequencing is less traumatic than bone marrow aspiration, and provides a less invasive method for monitoring the transcription characteristics of T cell changes in AL amyloidosis patients
.
The highlights of this study are the first in-depth study of the T cell lineage of patients with AL amyloidosis through single-cell sequencing; the second is the comparison of T cells in patients with AL amyloidosis and myeloma patients after using CD38 monoclonal antibody.
Change
.
The future research directions of AL amyloidosis include: the use of immunomodulators in AL amyloidosis, and the further exploration of the use of daratumumab, so as to further improve the efficacy and reduce toxic side effects and so on
.
Yimaitong: As the main investigator of the daratumomab international multi-center clinical study ANDROMEDA Phase III in China, would you please talk about the main findings of this study? The ANDROMEDA study is an open-label, randomized controlled phase III clinical trial that evaluates the efficacy and safety of daratumumab combined with bortezomib, cyclophosphamide and dexamethasone (D-VCd) regimen compared to VCd regimen
.
A total of 388 patients with newly diagnosed AL amyloidosis were included in the study, and they were randomly enrolled in the group at a ratio of 1:1
.
The just-concluded ASH conference reported on the 18-month milestone data analysis of the ANDROMEDA research
.
The primary endpoint of the study was the hematological response rate.
The complete response rate (CR) of the D-VCd group and VCd group were 59.
5% and 19.
2%, respectively
.
In addition to the hematological remission rate, the organ remission rate is also an important efficacy evaluation index
.
At the 6-month follow-up, the cardiac remission rate of the D-VCd group was 42% and the renal remission rate was 54%; the updated 18-month follow-up results showed that the D-VCd group had a cardiac remission rate of 53% and renal remission.
The rate is 58%
.
Among them, the cardiac remission rate increased significantly with the extension of the treatment time
.
(As shown in Figure 1) Figure 1.
ANDROMEDA Phase III study D-VCd group and VCd group efficacy evaluation ANDROMEDA Phase III clinical trial results show that daratumumab in the first-line treatment of newly diagnosed AL amyloidosis Excellent efficacy
.
With the extension of the study follow-up time, the proportion of patients with organ remission has increased significantly, especially for patients who have achieved deep hematological remission, the chance of organ remission may be higher
.
In addition, the study uses the CR rate of hematology as the primary endpoint of efficacy evaluation.
Compared with previous studies, it is easier to obtain progression-free survival (PFS) or overall response rate (ORR) as an indicator of efficacy evaluation, and it is also easier to evaluate early efficacy.
More precise
.
Yimaitong: Recently, as the corresponding author, you published a domestic multicenter retrospective study of daratumumab in patients with AL amyloidosis in the Chinese Journal of Internal Medicine
.
For Chinese patients with AL amyloidosis, what is the efficacy and safety of daratumumab? For the newly diagnosed AL amyloidosis patients included in the study, daratumomab has a significant effect, and the proportion of patients achieving ≥VGPR is 100%
.
Among patients with relapsed and refractory AL amyloidosis, 85.
7% (12/14) of the patients can achieve the effect of ≥VGPR
.
Patients with AL amyloidosis are usually in poor physical condition.
When they are treated with monoclonal antibodies, they may cause adverse events such as heart failure due to infusion reactions or excessive fluid infusion
.
During the treatment with daratumumab, no infusion reaction above grade 3 occurred, adverse reactions can be controlled, and the safety is good
.
Yimaitong: Could you please talk about the recently approved subcutaneous (SC) dosage form of daratumumab, compared with the intravenous (IV) dosage form, what are the differences in the clinical application of AL amyloidosis? The approval of the SC dosage form of daratumumab is mainly based on the phase III COLUMBA (MMY3012) study.
The ANDROMEDA phase III clinical trial also confirmed the efficacy and safety of the SC dosage form of daratumumab
.
In terms of efficacy, the SC dosage form of daratumomab is basically the same as the IV dosage form
.
In terms of safety, the incidence of infusion-related adverse reactions of the SC dosage form of darretuzumab is lower than that of the IV dosage form of daretuzumab, which is about 9%
.
In addition, the SC dosage form of daratumumab is characterized by a significant reduction in the amount of liquid infusion, and it can be quickly absorbed by the body after injection
.
Due to the high proportion of patients with AL amyloidosis complicated by heart disease and kidney disease, patients often have severe edema, and the requirements for fluid infusion are very high
.
The SC dosage form of daratumumab is the biggest benefit for these patients in clinical application
.
Summary The changes of T cell lineage before and after treatment with daratumumab in patients with AL amyloidosis have been revealed for the first time, and the relevant mechanism of action of daratumumab in the treatment of AL amyloidosis has been further elucidated
.
The latest results of ANDROMEDA's phase III clinical trial show the efficacy of daratumumab in the first-line treatment of newly diagnosed AL amyloidosis
.
Domestic multi-center retrospective studies have further verified the efficacy and safety of daratumumab in Chinese patients
.
Recently, the subcutaneous dosage form of daratumumab has been officially approved, and it is expected that it can bring clinical benefits to more Chinese patients with AL amyloidosis! Associate Professor Lu Jin, Chief Physician, Associate Professor, and Doctoral Supervisor Peking University People’s Hospital, Peking University Institute of Hematology, mainly for multiple myeloma, primary systemic amyloidosis, lymphoma, cellular immunotherapy, etc.
clinical and laboratory Research on the Director-General and Standing Committee Member of the Hematologists Branch of the Chinese Medical Doctor Association, and the Chairman of the Hematology Branch of the Beijing Medical Doctors Association, Deputy Chairman of the Multiple Myeloma Professional Committee of the Chinese Medical Doctor Association and Deputy Chairman of the Professional Committee of Tissue Cell Diseases, Deputy Director of the Hematology Branch of the Chinese Geriatrics Association Chairman and Chairman of the Multiple Myeloma Academic Committee, Deputy Leader of the Plasma Cytology Group of the Hematology Branch of the Chinese Medical Association Member of the China and International Primary Systemic Amyloidosis Collaboration Group International Myeloma Working Group, Asia Pacific Myeloma Working Group Member International The member of the Kidney and Monoclonal Immunoglobulin Disease Research Group stamped "read the original text" and we make progress together
