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Multiple myeloma (MM) is a highly heterogeneous malignant tumor with abnormal proliferation of clonal plasma cells
.
In recent years, with the advent of the era of new drugs and the improvement of medical technology, the enthusiasm for treatment of MM patients has been improved and the survival of MM patients has been effectively prolonged.
However, most MM patients are still facing primary drug resistance and disease recurrence.
The predicament of patients with relapse after multi-line therapy lacks effective treatment methods and has poor prognosis.
Drugs with a new mechanism are urgently needed to improve the treatment efficiency and survival prognosis of such patients
.
Selinexor (ATG-010), as the world's first approved oral selective inhibitor of nuclear export protein (SINE), targets a new tumor treatment mechanism and inhibits nuclear export protein 1 (SINE) in a slow and reversible manner ( XPO1), induces tumor cell apoptosis, and exhibits good anti-MM activity in clinical trials
.
Based on the unique mechanism of action and abundant clinical trial data of selinisol, it has been approved by the National Medical Products Administration (NMPA) of China for use in combination with dexamethasone for the treatment of previously treated patients with at least one proteasome inhibitor , an immunomodulator and an anti-CD38 mAb in relapsed/refractory MM
.
On this occasion, Yimaitong specially invited Dr.
Lu Minqiu from the Department of Hematology of Beijing Jishuitan Hospital to share the case experience of Selinesol in the treatment of MM, and Professor Bao Li commented on the case! A MM patient, male, 48 years old, has no special medical history.
In November 2014, the patient was seen in a foreign hospital because of "low back pain and limited bending after activities for one month".
Bone destruction, the initial diagnosis was MM
.
Baseline characteristics of the patient at initial diagnosis: blood IgG 46.
3g/L, κ light chain: 5170mg/dl, bone marrow showed clonal plasma cells 29%, bone marrow biopsy showed plasmacytoma
.
FISH showed that 1q21 amplification-positive cells accounted for 45%, and IgH (14q32) rearrangement-positive cells accounted for 12.
5%
.
G banding is a complex karyotype
.
Clinical diagnosis: MM IgG-κ type, DS stage is IIIA stage, ISS stage is stage II, first-line treatment from November 2014 to October 2015, bortezomib combined with doxorubicin and dexamethasone (PAD) regimen, a total of 7 courses Complete remission (CR) after 4 courses.
Second-line treatment.
From March 2016 to July 2016, lenalidomide combined with cyclophosphamide and dexamethasone (RCD), a total of 3 courses; lenalidomide combined with cyclophosphine Amide, dexamethasone and liposomal doxorubicin (RCAD) regimen, a total of 3 courses of efficacy evaluation reached very good partial remission (VGPR) on November 7, 2016 the first autologous hematopoietic stem cell transplantation (ASCT) efficacy evaluation reached VGPR, minimal residual disease (MRD) negative transplantation was consolidated with RACD regimen for 4 courses, and CR was achieved after consolidation, followed by lenalidomide maintenance therapy as third-line therapy.
From October 2018 to August 2019, bortezomib combined with cisplatin, polyamide Rirubicin liposome, cyclophosphamide, etoposide and dexamethasone (BDPACE) regimen, a total of 2 courses; BREPOCH regimen, a total of 2 courses, ixazomib combined with ibrutinib and dexamethasone (IZd) Program, a total of 3 courses of disease progression (PD), aggravation of low back pain June 3, 2019 Carfilzomib + Lenalidomide + Dexamethasone (KRD) program, a total of 2 courses of efficacy evaluation reached VGPR fourth-line treatment 2019 From September 2009 to May 2020, the disease progressed after the third course of KRD regimen, and the second ASCT efficacy evaluation reached VGPR.
One month later, daratumumab (Dara) combined with dexamethasone maintenance treatment was started for a total of 5 Monthly fifth-line treatment June 2020 to August 2020 Gemcitabine and oxaliplatin (GEMOX) regimen combined with anti-PD1 monoclonal antibody (tislelizumab) treatment for 2 months Efficacy evaluation was PDAugust 7, 2020 DARA combined with gemcitabine, oxaliplatin, liposomal doxorubicin and cisplatin for T6 tumor radiotherapy, T6 tumor shrinkage after radiotherapy The curative effect of previous regimens was summarized.
The patient had multi-line recurrence, multi-line chemotherapy, two transplants, each time After reaching the curative effect, the maintenance time is getting shorter and shorter.
Six-line treatment.
From October 2020 to April 2021, the regimen of selinesol combined with pomalidomide and dexamethasone (XPd), a total of 6 courses and 2 courses of treatment, the curative effect was evaluated.
Minimal remission (MR), the C2 tumor was reduced by 50%, the blood picture recovered, and the platelets were normal
.
On January 22, 2021, due to the patient's pathological fracture of the left distal humerus with a tumor, daratumumab combined with chemotherapy was added to the XPd regimen.
Due to severe bone marrow suppression after the combined chemotherapy, the patient was discontinued.
Toukomab, continued XPd treatment, the patient's left distal humerus tumor shrank, malunion
.
Left: The tumor appeared in the second cervical vertebra before XPd treatment; Right: Celinexol dosage and efficacy evaluation for cervical spondylosis reduction after XPd treatment.
Conclusion The patient is a MM patient who has received 5-line therapy in the past and is refractory to the later-line treatment.
Selinesol combined with pomalidomide and dexamethasone achieved curative effect, and the remission was maintained for 6 months.
It is an effective drug for the treatment of multi-line recurrent MM
.
Dr.
Lu Minqiu's diagnosis and treatment experience that Selinesol, as an oral selective inhibitor of nuclear export protein, specifically inhibits XPO1 in a slow and reversible manner, and exerts its unique anti-tumor activity mediated by at least three different pathways
.
First, selinesol can block the extranuclear export of key tumor suppressor proteins (TSPs) without hindering intranuclear transport, resulting in the accumulation and activation of TSPs in the nucleus to exert tumor suppressor functions; at the same time, it inhibits the expression of oncogenic protein mRNAs.
In the nucleus, it reduces the translation of oncogene protein mRNA in cytoplasmic ribosomes to synthesize oncoproteins, and reduces the level of oncoproteins in the cytoplasm; and Selinexol can activate the GR pathway and restore hormone sensitivity
.
Selinexor in combination with low-dose dexamethasone has been approved by the FDA for the treatment of at least 4 lines of therapy in patients whose disease is resistant to at least 2 proteasome inhibitors, at least 2 immunomodulators, and an anti-CD38 monoclonal Antibody-resistant relapsed or refractory adult MM patients bring more treatment options for relapsed and refractory MM patients
.
Selinexol combined with pomalidomide has a synergistic effect on the treatment of MM, and the XPd regimen has a good curative effect and tolerable adverse reactions in MM patients after multi-line recurrence
.
The patient has received six-line therapy, and the curative effect is still stable for half a year
.
Professor Bao Li commented that MM is a malignant proliferative disease of plasma cells.
With the advent of the new drug era, immunomodulators, proteasome inhibitors and CAR-T therapy have appeared one after another, and autologous hematopoietic stem cell transplantation has been widely used in clinical practice.
Both have brought more treatment options for MM patients and improved patient survival
.
However, conventional chemotherapy regimens in most patients can only achieve short-term remission of the disease, and patients who relapse after multi-line therapy still face the dilemma of drug resistance and no effective drugs to choose from
.
Therefore, for the treatment of MM, drugs with a new mechanism of action are urgently needed to improve the efficacy of patients
.
Selinesol is the world's first oral selective nuclear export inhibitor targeting a new mechanism of tumor treatment.
Its anti-tumor activity is mediated through at least three different pathways.
It inhibits cancer by targeting XPO1 to block the nuclear export of tumor suppressor proteins.
Cell division, inducing apoptosis of cancer cells, causing cancer cells to stop dividing and eventually die, without affecting the survival of normal cells
.
Based on its unique mechanism of action, the combination of selinesol and a variety of drugs also exhibits significant synergy to accelerate tumor cell apoptosis.
The guidelines for the diagnosis and treatment of hematological malignancies and the IMWG guidelines are recommended for the treatment of patients with relapsed and refractory MM
.
The patient in this case received 5 lines of therapy and 2 transplants in the past.
The depth of remission decreased significantly over time, and the time to remission was also significantly shortened after multi-line therapy and multi-line recurrence
.
Taking into account the patient's multidrug resistance, XPd chemotherapy was given.
After 1 course of treatment, the patient's neck pain disappeared.
After 2-3 courses of treatment, the patient's efficacy evaluation reached MR, the C2 tumor was reduced by 50%, and the remission time was as long as 6 years.
months, the efficacy is significant and the safety is controllable
.
The use of a regimen containing selenisol is an innovative clinical practice of a new targeted drug combined with chemotherapy, which brings an effective and safe new option for multi-line therapy and multi-line relapsed MM patients
.
Professor Bao Li Director, Chief Physician, Associate Professor, Department of Hematology, Beijing Jishuitan Hospital, Chairman of the Professional Committee of Translational Medicine, China Medical Education Association, Chairman of the Professional Committee of Hematology, Beijing Perioperative Medical Research Association, Standing Committee Member of the Professional Committee of Clinical Oncology, Chinese Women Physicians Association Member of the Lymphatic and Blood Professional Committee of the Society Member of the Standing Committee of the Youth Committee of the China Medical Education Hematology Committee Youth Member of the Hematology and Oncology Branch of the Chinese Women Physician Association Member of the Second Hematology Committee of the Beijing Association of Integrative Medicine
.
In recent years, with the advent of the era of new drugs and the improvement of medical technology, the enthusiasm for treatment of MM patients has been improved and the survival of MM patients has been effectively prolonged.
However, most MM patients are still facing primary drug resistance and disease recurrence.
The predicament of patients with relapse after multi-line therapy lacks effective treatment methods and has poor prognosis.
Drugs with a new mechanism are urgently needed to improve the treatment efficiency and survival prognosis of such patients
.
Selinexor (ATG-010), as the world's first approved oral selective inhibitor of nuclear export protein (SINE), targets a new tumor treatment mechanism and inhibits nuclear export protein 1 (SINE) in a slow and reversible manner ( XPO1), induces tumor cell apoptosis, and exhibits good anti-MM activity in clinical trials
.
Based on the unique mechanism of action and abundant clinical trial data of selinisol, it has been approved by the National Medical Products Administration (NMPA) of China for use in combination with dexamethasone for the treatment of previously treated patients with at least one proteasome inhibitor , an immunomodulator and an anti-CD38 mAb in relapsed/refractory MM
.
On this occasion, Yimaitong specially invited Dr.
Lu Minqiu from the Department of Hematology of Beijing Jishuitan Hospital to share the case experience of Selinesol in the treatment of MM, and Professor Bao Li commented on the case! A MM patient, male, 48 years old, has no special medical history.
In November 2014, the patient was seen in a foreign hospital because of "low back pain and limited bending after activities for one month".
Bone destruction, the initial diagnosis was MM
.
Baseline characteristics of the patient at initial diagnosis: blood IgG 46.
3g/L, κ light chain: 5170mg/dl, bone marrow showed clonal plasma cells 29%, bone marrow biopsy showed plasmacytoma
.
FISH showed that 1q21 amplification-positive cells accounted for 45%, and IgH (14q32) rearrangement-positive cells accounted for 12.
5%
.
G banding is a complex karyotype
.
Clinical diagnosis: MM IgG-κ type, DS stage is IIIA stage, ISS stage is stage II, first-line treatment from November 2014 to October 2015, bortezomib combined with doxorubicin and dexamethasone (PAD) regimen, a total of 7 courses Complete remission (CR) after 4 courses.
Second-line treatment.
From March 2016 to July 2016, lenalidomide combined with cyclophosphamide and dexamethasone (RCD), a total of 3 courses; lenalidomide combined with cyclophosphine Amide, dexamethasone and liposomal doxorubicin (RCAD) regimen, a total of 3 courses of efficacy evaluation reached very good partial remission (VGPR) on November 7, 2016 the first autologous hematopoietic stem cell transplantation (ASCT) efficacy evaluation reached VGPR, minimal residual disease (MRD) negative transplantation was consolidated with RACD regimen for 4 courses, and CR was achieved after consolidation, followed by lenalidomide maintenance therapy as third-line therapy.
From October 2018 to August 2019, bortezomib combined with cisplatin, polyamide Rirubicin liposome, cyclophosphamide, etoposide and dexamethasone (BDPACE) regimen, a total of 2 courses; BREPOCH regimen, a total of 2 courses, ixazomib combined with ibrutinib and dexamethasone (IZd) Program, a total of 3 courses of disease progression (PD), aggravation of low back pain June 3, 2019 Carfilzomib + Lenalidomide + Dexamethasone (KRD) program, a total of 2 courses of efficacy evaluation reached VGPR fourth-line treatment 2019 From September 2009 to May 2020, the disease progressed after the third course of KRD regimen, and the second ASCT efficacy evaluation reached VGPR.
One month later, daratumumab (Dara) combined with dexamethasone maintenance treatment was started for a total of 5 Monthly fifth-line treatment June 2020 to August 2020 Gemcitabine and oxaliplatin (GEMOX) regimen combined with anti-PD1 monoclonal antibody (tislelizumab) treatment for 2 months Efficacy evaluation was PDAugust 7, 2020 DARA combined with gemcitabine, oxaliplatin, liposomal doxorubicin and cisplatin for T6 tumor radiotherapy, T6 tumor shrinkage after radiotherapy The curative effect of previous regimens was summarized.
The patient had multi-line recurrence, multi-line chemotherapy, two transplants, each time After reaching the curative effect, the maintenance time is getting shorter and shorter.
Six-line treatment.
From October 2020 to April 2021, the regimen of selinesol combined with pomalidomide and dexamethasone (XPd), a total of 6 courses and 2 courses of treatment, the curative effect was evaluated.
Minimal remission (MR), the C2 tumor was reduced by 50%, the blood picture recovered, and the platelets were normal
.
On January 22, 2021, due to the patient's pathological fracture of the left distal humerus with a tumor, daratumumab combined with chemotherapy was added to the XPd regimen.
Due to severe bone marrow suppression after the combined chemotherapy, the patient was discontinued.
Toukomab, continued XPd treatment, the patient's left distal humerus tumor shrank, malunion
.
Left: The tumor appeared in the second cervical vertebra before XPd treatment; Right: Celinexol dosage and efficacy evaluation for cervical spondylosis reduction after XPd treatment.
Conclusion The patient is a MM patient who has received 5-line therapy in the past and is refractory to the later-line treatment.
Selinesol combined with pomalidomide and dexamethasone achieved curative effect, and the remission was maintained for 6 months.
It is an effective drug for the treatment of multi-line recurrent MM
.
Dr.
Lu Minqiu's diagnosis and treatment experience that Selinesol, as an oral selective inhibitor of nuclear export protein, specifically inhibits XPO1 in a slow and reversible manner, and exerts its unique anti-tumor activity mediated by at least three different pathways
.
First, selinesol can block the extranuclear export of key tumor suppressor proteins (TSPs) without hindering intranuclear transport, resulting in the accumulation and activation of TSPs in the nucleus to exert tumor suppressor functions; at the same time, it inhibits the expression of oncogenic protein mRNAs.
In the nucleus, it reduces the translation of oncogene protein mRNA in cytoplasmic ribosomes to synthesize oncoproteins, and reduces the level of oncoproteins in the cytoplasm; and Selinexol can activate the GR pathway and restore hormone sensitivity
.
Selinexor in combination with low-dose dexamethasone has been approved by the FDA for the treatment of at least 4 lines of therapy in patients whose disease is resistant to at least 2 proteasome inhibitors, at least 2 immunomodulators, and an anti-CD38 monoclonal Antibody-resistant relapsed or refractory adult MM patients bring more treatment options for relapsed and refractory MM patients
.
Selinexol combined with pomalidomide has a synergistic effect on the treatment of MM, and the XPd regimen has a good curative effect and tolerable adverse reactions in MM patients after multi-line recurrence
.
The patient has received six-line therapy, and the curative effect is still stable for half a year
.
Professor Bao Li commented that MM is a malignant proliferative disease of plasma cells.
With the advent of the new drug era, immunomodulators, proteasome inhibitors and CAR-T therapy have appeared one after another, and autologous hematopoietic stem cell transplantation has been widely used in clinical practice.
Both have brought more treatment options for MM patients and improved patient survival
.
However, conventional chemotherapy regimens in most patients can only achieve short-term remission of the disease, and patients who relapse after multi-line therapy still face the dilemma of drug resistance and no effective drugs to choose from
.
Therefore, for the treatment of MM, drugs with a new mechanism of action are urgently needed to improve the efficacy of patients
.
Selinesol is the world's first oral selective nuclear export inhibitor targeting a new mechanism of tumor treatment.
Its anti-tumor activity is mediated through at least three different pathways.
It inhibits cancer by targeting XPO1 to block the nuclear export of tumor suppressor proteins.
Cell division, inducing apoptosis of cancer cells, causing cancer cells to stop dividing and eventually die, without affecting the survival of normal cells
.
Based on its unique mechanism of action, the combination of selinesol and a variety of drugs also exhibits significant synergy to accelerate tumor cell apoptosis.
The guidelines for the diagnosis and treatment of hematological malignancies and the IMWG guidelines are recommended for the treatment of patients with relapsed and refractory MM
.
The patient in this case received 5 lines of therapy and 2 transplants in the past.
The depth of remission decreased significantly over time, and the time to remission was also significantly shortened after multi-line therapy and multi-line recurrence
.
Taking into account the patient's multidrug resistance, XPd chemotherapy was given.
After 1 course of treatment, the patient's neck pain disappeared.
After 2-3 courses of treatment, the patient's efficacy evaluation reached MR, the C2 tumor was reduced by 50%, and the remission time was as long as 6 years.
months, the efficacy is significant and the safety is controllable
.
The use of a regimen containing selenisol is an innovative clinical practice of a new targeted drug combined with chemotherapy, which brings an effective and safe new option for multi-line therapy and multi-line relapsed MM patients
.
Professor Bao Li Director, Chief Physician, Associate Professor, Department of Hematology, Beijing Jishuitan Hospital, Chairman of the Professional Committee of Translational Medicine, China Medical Education Association, Chairman of the Professional Committee of Hematology, Beijing Perioperative Medical Research Association, Standing Committee Member of the Professional Committee of Clinical Oncology, Chinese Women Physicians Association Member of the Lymphatic and Blood Professional Committee of the Society Member of the Standing Committee of the Youth Committee of the China Medical Education Hematology Committee Youth Member of the Hematology and Oncology Branch of the Chinese Women Physician Association Member of the Second Hematology Committee of the Beijing Association of Integrative Medicine
