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The 18th International Myeloma Symposium (IMW) in 2021 will be held on September 8-11 in a combination of online and offline methods
.
The conference brought together myeloma experts from all over the world and announced the results of a number of blockbuster studies
.
At this conference, a CPT (recombinant allosteric human tumor necrosis factor-related apoptosis-inducing ligand) combined with thalidomide and dexamethasone in the treatment of relapsed and refractory multiple myeloma (RRMM) by the team of Professor Chen Wenming Selected for poster presentation
.
On this occasion, Yimaitong has the honor to invite Professor Chen Wenming from the Department of Hematology, Beijing Chaoyang Hospital, Capital Medical University, to share his views on the research progress of RRMM at this IMW conference
.
Yimaitong: In the current era of new drugs, what is the current status of RRMM treatment? Professor Chen Wenming has been approved 15 new drugs for the treatment of MM since 2000
.
At present, the treatment options for MM are gradually increasing, and the efficacy of MM patients has also been improved.
However, the current new drug regimen can only prolong the survival of MM patients and cannot be cured
.
Regardless of the effect of MM patients, the disease will eventually relapse and progress
.
Therefore, relevant research is still exploring new mechanisms of action and new drugs to further improve the efficacy of MM patients, prolong survival, and bring about a cure
.
Yimaitong: CPT (recombinant allosteric human tumor necrosis factor-related apoptosis-inducing ligand) is a new peptide-targeted drug targeting the tumor death receptor pathway.
At present, many studies are devoted to exploring CPT in the treatment of RRMM Application
.
Could you please introduce the mechanism of CPT? Professor Chen Wenming currently knows that multiple pathways can control the apoptosis of MM cells.
The proteasome pathway is the main pathway for the proliferation of MM cells.
Therefore, proteasome inhibitors are effective in treating MM
.
In addition to the proteasome pathway, the death receptor pathway can also regulate the apoptosis of MM cells
.
After the proteasome pathway is inhibited, the death receptor pathway may be activated and become the main pathway for MM cell proliferation
.
The activation of the death receptor pathway can induce cell apoptosis through mitochondrial dependence and secretion
.
CPT can induce MM cell apoptosis by blocking the death receptor pathway
.
Since the proliferation of MM cells in most MM patients depends on the proteasome pathway, the activity of CPT in this part of patients is not obvious
.
But for RRMM patients whose proteasome pathway is inhibited, MM cell proliferation depends on the death receptor pathway
.
CPT can effectively block the death receptor pathway, induce apoptosis of MM cells, and obtain better curative effects
.
Yimaitong: The results of the Phase III study of CPT combined with thalidomide and dexamethasone in the treatment of RRMM reported by you and your team at this IMW meeting have proved the excellent efficacy and good safety of the combined program.
Can you please Interpret this research in detail? And talk about the treatment prospects of CPT for RRMM patients? In fact, Professor Chen Wenming has carried out a number of studies on CPT abroad, but because the CPT used in the related research is wild-type and has a short half-life, the curative effect is not good, and the related research is basically terminated in phase I/II
.
The domestically developed CPT has innovated the structure, prolonged the half-life of CPT, and at the same time enhanced its activity.
Compared with the CPT in foreign I/II studies, the anti-tumor activity of CPT is stronger
.
Phase I/II clinical studies conducted in China show that the overall response rate (ORR) of CPT treatment of RRMM patients is about 20%-30%
.
Considering that the ORR of many new drugs in the field of RRMM (such as bortezomib, carfilzomib, pomalidomide, daretuzumab) in the treatment of RRMM does not exceed 30%, the CPT is studied in Phase I/II The ORR shown in this article is worthy of attention
.
Considering the small number of patients included in the phase I/II study, the phase III study included more RRMM patients and explored the efficacy of the CPT combination regimen in RRMM patients
.
Due to the early design of the Phase III study and the lack of new drug options, the study finally compared the CPT combined with thalidomide, dexamethasone (CPT+TD) regimen and thalidomide combined with dexamethasone (TD) regimen in RRMM The curative effect in patients is to explore whether CPT and other MM treatment drugs have a synergistic effect to promote the apoptosis of MM cells
.
The results of the study show that CPT has good anti-tumor activity in RRMM patients
.
The progression-free survival (PFS) of patients in the CPT+TD group was longer than that in the TD group (5.
5 months vs 2.
4 months)
.
The CPT+TD combined program reduced the risk of disease progression in RRMM patients by 38%, and prolonged the overall survival (OS) of RRMM patients (21.
8 months vs 17 months)
.
The ORR (30.
4% vs 13.
7%) of the CPT+TD group and the very good partial remission and above (≥VGPR) rate (12.
1% vs 2.
1%) were also higher
.
Due to the low expression of most normal cell death receptors, CPT is safe in RRMM patients
.
However, due to the expression of death receptors in liver cells, RRMM patients have a certain degree of liver damage after CPT treatment.
However, the liver damage that occurred after the first cycle of treatment in the study was low in grade and controllable
.
Overall, CPT has considerable efficacy and safety in RRMM
.
Yimaitong: In your opinion, what new directions are worth exploring in the treatment of RRMM in the future? Professor Chen Wenming has seen many new drugs in the field of MM treatment in recent years.
As time goes by, more new drugs will be launched in the future
.
With the increase of new drugs in the field of MM treatment, it is necessary to carry out more clinical studies to explore the use of different new drugs in combination or sequential programs in RRMM patients, which will bring better curative effects for RRMM patients, and even bring cures for RRMM patients
.
In recent years, the target of BCMA has been a research hotspot in the field of RRMM.
Related drugs such as antibody-drug conjugates, bispecific antibodies, chimeric antigen receptor T cell (CAR-T) immunotherapy have also shown considerable efficacy in RRMM
.
In the future, it is also necessary to explore the combination of these new drugs and new therapies, combined with traditional targeted drugs, cytotoxic drugs, hematopoietic stem cell transplantation, etc.
, to bring more clinical benefits to RRMM patients
.
Yimaitong: In your opinion, what other RRMM research developments at this year's IMW conference are worth paying attention to? Professor Chen Wenming, due to the short interval between this IMW conference and other recent academic conferences, so there are not too many new research results announced at this IMW conference
.
However, this conference also announced the research progress of many related drugs for BCMA targets.
In addition, the research progress of a new generation of immunomodulator Avadomide in RRMM is also worthy of attention
.
At present, China has also carried out a number of clinical researches on related drugs targeting the BCMA target, and the relevant research progress was also reported at this IMW conference
.
We look forward to more breakthroughs in related research in the future, which will bring better clinical options and more clinical benefits to RRMM patients
.
Professor Chen Wenming Chief Physician, Professor, Doctor of Medicine, Doctoral Supervisor, Director of the Department of Hematology, Beijing Chaoyang Hospital, Capital Medical University, Director of Beijing Multiple Myeloma Medical Research Center, Director of the Department of Hematology, Capital Medical University, Consultant of the International Myeloma Working Group and China Multiple Myeloma Working Group Expert Committee Member of the Hematology Professional Committee of China Medical Education Association Member of the Standing Committee of the Hematology Branch of the Chinese Integrative Medicine Association Member of the Standing Committee of the Hematology Branch of the Chinese Society of Geriatrics Member of the Transplantation Group, Member of the Hematology and Tumor Branch of the Chinese Anti-Cancer Association
.
The conference brought together myeloma experts from all over the world and announced the results of a number of blockbuster studies
.
At this conference, a CPT (recombinant allosteric human tumor necrosis factor-related apoptosis-inducing ligand) combined with thalidomide and dexamethasone in the treatment of relapsed and refractory multiple myeloma (RRMM) by the team of Professor Chen Wenming Selected for poster presentation
.
On this occasion, Yimaitong has the honor to invite Professor Chen Wenming from the Department of Hematology, Beijing Chaoyang Hospital, Capital Medical University, to share his views on the research progress of RRMM at this IMW conference
.
Yimaitong: In the current era of new drugs, what is the current status of RRMM treatment? Professor Chen Wenming has been approved 15 new drugs for the treatment of MM since 2000
.
At present, the treatment options for MM are gradually increasing, and the efficacy of MM patients has also been improved.
However, the current new drug regimen can only prolong the survival of MM patients and cannot be cured
.
Regardless of the effect of MM patients, the disease will eventually relapse and progress
.
Therefore, relevant research is still exploring new mechanisms of action and new drugs to further improve the efficacy of MM patients, prolong survival, and bring about a cure
.
Yimaitong: CPT (recombinant allosteric human tumor necrosis factor-related apoptosis-inducing ligand) is a new peptide-targeted drug targeting the tumor death receptor pathway.
At present, many studies are devoted to exploring CPT in the treatment of RRMM Application
.
Could you please introduce the mechanism of CPT? Professor Chen Wenming currently knows that multiple pathways can control the apoptosis of MM cells.
The proteasome pathway is the main pathway for the proliferation of MM cells.
Therefore, proteasome inhibitors are effective in treating MM
.
In addition to the proteasome pathway, the death receptor pathway can also regulate the apoptosis of MM cells
.
After the proteasome pathway is inhibited, the death receptor pathway may be activated and become the main pathway for MM cell proliferation
.
The activation of the death receptor pathway can induce cell apoptosis through mitochondrial dependence and secretion
.
CPT can induce MM cell apoptosis by blocking the death receptor pathway
.
Since the proliferation of MM cells in most MM patients depends on the proteasome pathway, the activity of CPT in this part of patients is not obvious
.
But for RRMM patients whose proteasome pathway is inhibited, MM cell proliferation depends on the death receptor pathway
.
CPT can effectively block the death receptor pathway, induce apoptosis of MM cells, and obtain better curative effects
.
Yimaitong: The results of the Phase III study of CPT combined with thalidomide and dexamethasone in the treatment of RRMM reported by you and your team at this IMW meeting have proved the excellent efficacy and good safety of the combined program.
Can you please Interpret this research in detail? And talk about the treatment prospects of CPT for RRMM patients? In fact, Professor Chen Wenming has carried out a number of studies on CPT abroad, but because the CPT used in the related research is wild-type and has a short half-life, the curative effect is not good, and the related research is basically terminated in phase I/II
.
The domestically developed CPT has innovated the structure, prolonged the half-life of CPT, and at the same time enhanced its activity.
Compared with the CPT in foreign I/II studies, the anti-tumor activity of CPT is stronger
.
Phase I/II clinical studies conducted in China show that the overall response rate (ORR) of CPT treatment of RRMM patients is about 20%-30%
.
Considering that the ORR of many new drugs in the field of RRMM (such as bortezomib, carfilzomib, pomalidomide, daretuzumab) in the treatment of RRMM does not exceed 30%, the CPT is studied in Phase I/II The ORR shown in this article is worthy of attention
.
Considering the small number of patients included in the phase I/II study, the phase III study included more RRMM patients and explored the efficacy of the CPT combination regimen in RRMM patients
.
Due to the early design of the Phase III study and the lack of new drug options, the study finally compared the CPT combined with thalidomide, dexamethasone (CPT+TD) regimen and thalidomide combined with dexamethasone (TD) regimen in RRMM The curative effect in patients is to explore whether CPT and other MM treatment drugs have a synergistic effect to promote the apoptosis of MM cells
.
The results of the study show that CPT has good anti-tumor activity in RRMM patients
.
The progression-free survival (PFS) of patients in the CPT+TD group was longer than that in the TD group (5.
5 months vs 2.
4 months)
.
The CPT+TD combined program reduced the risk of disease progression in RRMM patients by 38%, and prolonged the overall survival (OS) of RRMM patients (21.
8 months vs 17 months)
.
The ORR (30.
4% vs 13.
7%) of the CPT+TD group and the very good partial remission and above (≥VGPR) rate (12.
1% vs 2.
1%) were also higher
.
Due to the low expression of most normal cell death receptors, CPT is safe in RRMM patients
.
However, due to the expression of death receptors in liver cells, RRMM patients have a certain degree of liver damage after CPT treatment.
However, the liver damage that occurred after the first cycle of treatment in the study was low in grade and controllable
.
Overall, CPT has considerable efficacy and safety in RRMM
.
Yimaitong: In your opinion, what new directions are worth exploring in the treatment of RRMM in the future? Professor Chen Wenming has seen many new drugs in the field of MM treatment in recent years.
As time goes by, more new drugs will be launched in the future
.
With the increase of new drugs in the field of MM treatment, it is necessary to carry out more clinical studies to explore the use of different new drugs in combination or sequential programs in RRMM patients, which will bring better curative effects for RRMM patients, and even bring cures for RRMM patients
.
In recent years, the target of BCMA has been a research hotspot in the field of RRMM.
Related drugs such as antibody-drug conjugates, bispecific antibodies, chimeric antigen receptor T cell (CAR-T) immunotherapy have also shown considerable efficacy in RRMM
.
In the future, it is also necessary to explore the combination of these new drugs and new therapies, combined with traditional targeted drugs, cytotoxic drugs, hematopoietic stem cell transplantation, etc.
, to bring more clinical benefits to RRMM patients
.
Yimaitong: In your opinion, what other RRMM research developments at this year's IMW conference are worth paying attention to? Professor Chen Wenming, due to the short interval between this IMW conference and other recent academic conferences, so there are not too many new research results announced at this IMW conference
.
However, this conference also announced the research progress of many related drugs for BCMA targets.
In addition, the research progress of a new generation of immunomodulator Avadomide in RRMM is also worthy of attention
.
At present, China has also carried out a number of clinical researches on related drugs targeting the BCMA target, and the relevant research progress was also reported at this IMW conference
.
We look forward to more breakthroughs in related research in the future, which will bring better clinical options and more clinical benefits to RRMM patients
.
Professor Chen Wenming Chief Physician, Professor, Doctor of Medicine, Doctoral Supervisor, Director of the Department of Hematology, Beijing Chaoyang Hospital, Capital Medical University, Director of Beijing Multiple Myeloma Medical Research Center, Director of the Department of Hematology, Capital Medical University, Consultant of the International Myeloma Working Group and China Multiple Myeloma Working Group Expert Committee Member of the Hematology Professional Committee of China Medical Education Association Member of the Standing Committee of the Hematology Branch of the Chinese Integrative Medicine Association Member of the Standing Committee of the Hematology Branch of the Chinese Society of Geriatrics Member of the Transplantation Group, Member of the Hematology and Tumor Branch of the Chinese Anti-Cancer Association
