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Multiple myeloma (MM) is a malignant tumor with abnormal proliferation of plasma cells, which is more common in the elderly and cannot be completely cured at present
.
In recent years, the continuous progress of therapeutic drugs such as proteasome inhibitors, immunomodulators, and monoclonal antibodies has led to a significant improvement in the survival rate of MM patients
.
In addition, with the continuous emergence of new drugs, hematopoietic stem cell transplantation still plays an important role in the treatment of MM patients
.
At the beginning of the new year in 2022, Yimaitong specially invited Professor Huang Wenrong of PLA General Hospital for an interview to review the progress of MM treatment in 2021, and share his views on the future development of MM treatment and the role of autologous hematopoietic stem cell transplantation (ASCT) in MM
.
In 2021, the field of MM will continue to progress.
First of all, it is worth mentioning that, with the promotion of the Chinese Medical Association, the Chinese Society of Clinical Oncology (CSCO) and other societies and related companies, the whole-process management of MM can be promoted and popularized nationwide.
, so that doctors in the field of MM in China, especially the grass-roots doctors, have a clearer concept and understanding of the whole-process management of MM
.
In addition, under the leadership of Director Ma Jun and Secretary Zhu Jun, China has established a registration bank for autologous hematopoietic stem cell transplantation, with more than 300 participating units, covering most city hospitals and some county-level hospitals, which is conducive to understanding ASCT The application of MM treatment in China, its efficacy and the occurrence of complications have practical guiding significance
.
In addition, there are several noteworthy events with regard to therapeutic drugs
.
In December 2021, the CD38 monoclonal antibody daratumumab was included in the medical insurance, reducing the medical burden on patients and improving the availability of medicines for the masses
.
The proteasome inhibitor carfilzomib and the small molecule drug XPO1 inhibitor selenisol have also been approved for marketing, adding a new "weapon" to the treatment of MM
.
After the launch of the immunomodulator pomalidomide in November 2020, some researchers have carried out relevant clinical studies, such as bortezomib, pomalidomide, and dexamethasone (VPd) regimen for patients with MM with renal insufficiency Induction therapy of 2019 has also achieved good curative effect, and related reports were made at the 2021 ASH meeting
.
In addition, CAR-T cells are an epoch-making "landmark" cellular immunotherapy.
In March 2021, the U.
S.
Food and Drug Administration (FDA) approved the CAR-T cell therapy idecabtagene vicleucel for the treatment of patients who have received ≥ 4 lines Relapsed/refractory MM adult patients with therapy (including immunomodulators, proteasome inhibitors and anti-CD38 monoclonal antibodies), which also promotes the research of CAR-T cell therapy for MM in China
.
ASCT is still of great value in the treatment of MM.
Since ASCT began to be used in the treatment of MM in the early 1980s, the overall survival (OS) of patients has been significantly prolonged.
Therefore, ASCT has been considered as the best choice for newly diagnosed MM patients aged ≤65 years old.
Preferred treatment option
.
According to foreign statistics, the median age of onset of MM patients is 69 years old, and the median age of onset is much higher than that of domestic patients.
However, compared with the transplant rate of foreign MM patients (about 60%-70%), there are very few patients in China who undergo ASCT (few).
In order to narrow the gap with foreign countries, Professor Huang Wenrong expressed the hope that domestic myeloma workers will pay more attention to and actively carry out the application of ASCT in the treatment of MM, so that hospitals with limited medical conditions can correctly guide patients to larger hospitals.
For transplant treatment in medical centers, relevant hospitals with relevant hardware facilities such as transplant wards and laminar flow beds (laminar flow hoods) can actively promote the application of ASCT
.
In addition, relevant medical workers need to be trained so that they are familiar with the transplantation process and complications during transplantation, and have the skills to deal with related complications in a timely manner
.
So, can elderly patients undergo ASCT? Professor Huang Wenrong shared the recent case of a 72-year-old patient who successfully performed ASCT with his team: after a comprehensive evaluation of the patient, the patient's condition was permitted, the transplant process went smoothly, the patient's disease was controlled within two weeks, and the patient did not occur after being discharged from the hospital.
related complications
.
Professor Huang Wenrong said that pre-transplant comprehensive evaluation of elderly patients is more important, and elderly MM patients who are eligible after evaluation can benefit from ASCT
.
In addition, about 30%-40% of MM patients have renal insufficiency.
Is it safe to perform ASCT in MM patients with renal insufficiency? Does renal insufficiency worsen after ASCT? How should MM patients with renal insufficiency be transplanted? Professor Huang Wenrong said that these are a test for clinicians
.
MM patients with renal insufficiency may experience life-threatening conditions during transplantation, and therefore require comprehensive management of patients by experienced physicians
.
Professor Huang Wenrong and his team are summarizing relevant experience and planning to promote it nationwide, so that more patients can benefit from ASCT
.
The prospect of MM treatment is promising.
With the continuous emergence and application of new drugs, more solutions have been explored in the field of MM treatment, including how to better apply new proteasome inhibitors, immunomodulators, and CD38 monoclonal combination regimens, so that the initial Patients with relapsed or refractory MM have better efficacy in induction therapy
.
In addition to new small-molecule targeted drugs, in recent years, the efficacy of CAR-T cells in the treatment of MM has also become more prominent.
At present, the remission rate of CAR-T cells targeting B cell maturation antigen (BCMA) is about 70%, and complete remission is achieved.
(CR) rate is about 20%-30%
.
In addition to the most commonly used BCMA targets, relevant studies on alternative antigenic sites such as GPRC5D and FcRH5 are also in progress, and at the same time, studies on synergistic combination of these antigenic targets with different costimulatory molecules (CD28, 41BB) are also in progress
.
Both bispecific antibodies and CAR-T use T cells to kill tumor cells.
Bispecific antibodies are equivalent to a bridge that binds to antigen sites on myeloma cells and T cells to activate T cell immunity and induce myeloma cells.
Cracking
.
Research on bispecific antibody treatment of MM is also being carried out in China.
Bispecific antibody not only has important value in the treatment of lymphoma and leukemia, but also has considerable prospects in the treatment of MM
.
Finally, Professor Huang Wenrong said again that there is still no new drug regimen that can replace the traditional and effective treatment method of ASCT
.
Actively promoting ASCT in the treatment of MM patients, especially the elderly, renal insufficiency and high-risk patients, is of great value
.
Professor Huang Wenrong, MD, Chief Physician, Postgraduate Supervisor The project leader of the Standing Committee of the Blood Precision Diagnosis and Treatment Committee of the Chinese Research Hospital Association is responsible for the National Natural Science Foundation of China, the military project, and the capital health development scientific research project
.
The first author or corresponding author of 1 second prize of the Army Science and Technology Progress Award has published 21 clinical SCI papers in international journals such as Oncogene, Bone marrow transplant, Cell Transplantation, Frontier Oncology, Transfusion, Annals of Hematology, Clinical transplant, Leukemia & lymphoma, etc.
More than 50 papers published in domestic journals, poke "read the original text", let's make progress together
.
In recent years, the continuous progress of therapeutic drugs such as proteasome inhibitors, immunomodulators, and monoclonal antibodies has led to a significant improvement in the survival rate of MM patients
.
In addition, with the continuous emergence of new drugs, hematopoietic stem cell transplantation still plays an important role in the treatment of MM patients
.
At the beginning of the new year in 2022, Yimaitong specially invited Professor Huang Wenrong of PLA General Hospital for an interview to review the progress of MM treatment in 2021, and share his views on the future development of MM treatment and the role of autologous hematopoietic stem cell transplantation (ASCT) in MM
.
In 2021, the field of MM will continue to progress.
First of all, it is worth mentioning that, with the promotion of the Chinese Medical Association, the Chinese Society of Clinical Oncology (CSCO) and other societies and related companies, the whole-process management of MM can be promoted and popularized nationwide.
, so that doctors in the field of MM in China, especially the grass-roots doctors, have a clearer concept and understanding of the whole-process management of MM
.
In addition, under the leadership of Director Ma Jun and Secretary Zhu Jun, China has established a registration bank for autologous hematopoietic stem cell transplantation, with more than 300 participating units, covering most city hospitals and some county-level hospitals, which is conducive to understanding ASCT The application of MM treatment in China, its efficacy and the occurrence of complications have practical guiding significance
.
In addition, there are several noteworthy events with regard to therapeutic drugs
.
In December 2021, the CD38 monoclonal antibody daratumumab was included in the medical insurance, reducing the medical burden on patients and improving the availability of medicines for the masses
.
The proteasome inhibitor carfilzomib and the small molecule drug XPO1 inhibitor selenisol have also been approved for marketing, adding a new "weapon" to the treatment of MM
.
After the launch of the immunomodulator pomalidomide in November 2020, some researchers have carried out relevant clinical studies, such as bortezomib, pomalidomide, and dexamethasone (VPd) regimen for patients with MM with renal insufficiency Induction therapy of 2019 has also achieved good curative effect, and related reports were made at the 2021 ASH meeting
.
In addition, CAR-T cells are an epoch-making "landmark" cellular immunotherapy.
In March 2021, the U.
S.
Food and Drug Administration (FDA) approved the CAR-T cell therapy idecabtagene vicleucel for the treatment of patients who have received ≥ 4 lines Relapsed/refractory MM adult patients with therapy (including immunomodulators, proteasome inhibitors and anti-CD38 monoclonal antibodies), which also promotes the research of CAR-T cell therapy for MM in China
.
ASCT is still of great value in the treatment of MM.
Since ASCT began to be used in the treatment of MM in the early 1980s, the overall survival (OS) of patients has been significantly prolonged.
Therefore, ASCT has been considered as the best choice for newly diagnosed MM patients aged ≤65 years old.
Preferred treatment option
.
According to foreign statistics, the median age of onset of MM patients is 69 years old, and the median age of onset is much higher than that of domestic patients.
However, compared with the transplant rate of foreign MM patients (about 60%-70%), there are very few patients in China who undergo ASCT (few).
In order to narrow the gap with foreign countries, Professor Huang Wenrong expressed the hope that domestic myeloma workers will pay more attention to and actively carry out the application of ASCT in the treatment of MM, so that hospitals with limited medical conditions can correctly guide patients to larger hospitals.
For transplant treatment in medical centers, relevant hospitals with relevant hardware facilities such as transplant wards and laminar flow beds (laminar flow hoods) can actively promote the application of ASCT
.
In addition, relevant medical workers need to be trained so that they are familiar with the transplantation process and complications during transplantation, and have the skills to deal with related complications in a timely manner
.
So, can elderly patients undergo ASCT? Professor Huang Wenrong shared the recent case of a 72-year-old patient who successfully performed ASCT with his team: after a comprehensive evaluation of the patient, the patient's condition was permitted, the transplant process went smoothly, the patient's disease was controlled within two weeks, and the patient did not occur after being discharged from the hospital.
related complications
.
Professor Huang Wenrong said that pre-transplant comprehensive evaluation of elderly patients is more important, and elderly MM patients who are eligible after evaluation can benefit from ASCT
.
In addition, about 30%-40% of MM patients have renal insufficiency.
Is it safe to perform ASCT in MM patients with renal insufficiency? Does renal insufficiency worsen after ASCT? How should MM patients with renal insufficiency be transplanted? Professor Huang Wenrong said that these are a test for clinicians
.
MM patients with renal insufficiency may experience life-threatening conditions during transplantation, and therefore require comprehensive management of patients by experienced physicians
.
Professor Huang Wenrong and his team are summarizing relevant experience and planning to promote it nationwide, so that more patients can benefit from ASCT
.
The prospect of MM treatment is promising.
With the continuous emergence and application of new drugs, more solutions have been explored in the field of MM treatment, including how to better apply new proteasome inhibitors, immunomodulators, and CD38 monoclonal combination regimens, so that the initial Patients with relapsed or refractory MM have better efficacy in induction therapy
.
In addition to new small-molecule targeted drugs, in recent years, the efficacy of CAR-T cells in the treatment of MM has also become more prominent.
At present, the remission rate of CAR-T cells targeting B cell maturation antigen (BCMA) is about 70%, and complete remission is achieved.
(CR) rate is about 20%-30%
.
In addition to the most commonly used BCMA targets, relevant studies on alternative antigenic sites such as GPRC5D and FcRH5 are also in progress, and at the same time, studies on synergistic combination of these antigenic targets with different costimulatory molecules (CD28, 41BB) are also in progress
.
Both bispecific antibodies and CAR-T use T cells to kill tumor cells.
Bispecific antibodies are equivalent to a bridge that binds to antigen sites on myeloma cells and T cells to activate T cell immunity and induce myeloma cells.
Cracking
.
Research on bispecific antibody treatment of MM is also being carried out in China.
Bispecific antibody not only has important value in the treatment of lymphoma and leukemia, but also has considerable prospects in the treatment of MM
.
Finally, Professor Huang Wenrong said again that there is still no new drug regimen that can replace the traditional and effective treatment method of ASCT
.
Actively promoting ASCT in the treatment of MM patients, especially the elderly, renal insufficiency and high-risk patients, is of great value
.
Professor Huang Wenrong, MD, Chief Physician, Postgraduate Supervisor The project leader of the Standing Committee of the Blood Precision Diagnosis and Treatment Committee of the Chinese Research Hospital Association is responsible for the National Natural Science Foundation of China, the military project, and the capital health development scientific research project
.
The first author or corresponding author of 1 second prize of the Army Science and Technology Progress Award has published 21 clinical SCI papers in international journals such as Oncogene, Bone marrow transplant, Cell Transplantation, Frontier Oncology, Transfusion, Annals of Hematology, Clinical transplant, Leukemia & lymphoma, etc.
More than 50 papers published in domestic journals, poke "read the original text", let's make progress together
