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In June 2021, a retrospective study published in "Oncol Ther" searched the literature to retrospectively analyze the maintenance treatment plan for patients with myeloma after transplantation
.
Friends who want to know the specific content, let us follow the editor and take a look! Research background Patients with myeloma still have a risk of recurrence after autologous stem cell transplantation (ASCT), and maintenance therapy after transplantation is needed to prolong the remission rate
.
After the initial diagnosis and risk stratification, the patient receives a multi-drug combination initial treatment, usually proteasome inhibitors and immunomodulatory drugs (IMiD), suitable for transplant patients to receive high-dose chemotherapy, and then autologous stem cell transplantation
.
The purpose of the research is to retrieve relevant literature, analyze and verify different maintenance treatment options after stem cell transplantation in patients with myeloma
.
Research methods: PubMed, the Cochrane Library, and the Evidence-Based Medicine Database (EBMR) were used to retrieve literature published between 2000 and 2009, as well as abstracts from American Society of Hematology/American Society of Clinical Oncology (ASH/ASCO) meetings and ongoing clinical trials
.
Article types include: Phase II, Phase III, and Phase IV clinical trials, randomized controlled trials (RTCs), retrospective/prospective studies, conference abstracts, and meta-analysis
.
A preliminary search of 110 articles on the use of maintenance therapy in adult patients with multiple myeloma was conducted.
After preliminary review, 55 abstracts/manuscripts were included for further analysis (Figure 1)
.
This article is based on previous research and does not include any new research on humans or animals
.
The results of the study in the late 1970s, the use of chemotherapy drugs as maintenance treatment did not prolong the survival of patients
.
In 1988, a randomized trial comparing the effectiveness of melphalan combined with prednisone maintenance treatment and non-maintenance treatment for MM patients showed that patients in the non-maintenance treatment group relapsed earlier, and the patients were treated with melphalan plus prednisone There is still a response, but it has no effect on OS; because the combination of melphalan will increase the toxicity, the use of melphalan-based maintenance therapy has not been applied to the clinic
.
Interferon: Some studies have shown that interferon α-2b maintenance treatment can enhance response and improve survival; but some studies have shown that interferon brings significant adverse effects; two landmark meta-analysis shows that interferon brings small survival benefits at the same time Accompanied by huge toxicity, it significantly affects the quality of life of patients
.
Therefore, the use of interferon for maintenance therapy is not recommended
.
Thalidomide: Two large-scale RCT studies in 2006, induction therapy and maintenance therapy with thalidomide after ASCT, showed that maintenance therapy with thalidomide can improve event-free survival and OS
.
In the HOVON-50 randomized phase III trial, compared with interferon, thalidomide maintenance treatment significantly prolonged PFS and improved OS; however, long-term follow-up results found that thalidomide maintenance treatment prolonged event-free survival compared with the control group.
Significantly toxic
.
Based on the limited access to IMiDs and proteasome inhibitors in developing countries, thalidomide can still be used as one of the maintenance treatment options after ASCT in these countries
.
Lenalidomide: In February 2017, the FDA approved lenalidomide for the maintenance treatment of MM patients after ASCT.
Common side effects are hematological adverse events such as cytopenia
.
It is recommended that a single ASCT and lenalidomide maintenance treatment be used as the standard care for patients receiving lenalidomide + bortezomib + dexamethasone (VRD) induction therapy
.
Currently, lenalidomide is an option for maintenance treatment after ASCT
.
Proteasome inhibitor: Bortezomib HOVON-65/GMMG-HD4 test showed that ASCT and bortezomib maintenance treatment after PAD (bortezomib, doxorubicin, dexamethasone) induction therapy can significantly prolong PFS and OS ; High-risk subgroup patients (nephropathy patients with chromosome 17p13 deletion and serum creatinine value exceeding 2 mg/dl) also have survival benefits
.
Therefore, bortezomib is a potential maintenance treatment option for prolonging PFS after ASCT, especially in high-risk patients
.
Ixazomib is administered orally once a week and can be used for the maintenance treatment of bortezomib-resistant and high-risk myeloma patients
.
The TOURMALINE-MM3 phase III trial showed that the induction treatment of newly diagnosed myeloma patients and the maintenance treatment of ixazomib after ASCT significantly prolonged PFS compared with the placebo group, which were 30.
7 months and 24.
9 months, respectively; the incidence of grade 3 adverse events was low (infection , Neutropenia, thrombocytopenia, peripheral neuropathy)
.
Ixazomib has good tolerability, convenient administration, low incidence of second malignant tumors, and significantly improves PFS.
It is a valuable maintenance option after ASCT
.
As a second-generation proteasome inhibitor, Carfilzomib has excellent efficacy
.
A phase I/II study showed that carfilzomib + lenalidomide + low-dose dexamethasone (CRd) is well tolerated and prolonged PFS after induction and maintenance therapy; another phase I/II study It has been shown that the use of carfilzomib + melphalan, ASCT and carfilzomib maintenance treatment in patients with recurrent myeloma brings PFS and OS benefits
.
Monoclonal antibodies: The anti-SLAMF7 antibody Errotuzumab and the anti-CD38 antibody Daratumumab were approved by the FDA for the treatment of myeloma patients in 2015
.
Erotuzumab + lenalidomide has satisfactory results and is well tolerated; Daratumumab as a first-line induction therapy can improve the remission rate and the depth of response without affecting the percentage of stem cell collection; LYRA research shows , Newly diagnosed and relapsed MM patients with daretuzumab + bortezomib + cyclophosphamide + dexamethasone induction therapy, ASCT and daretuzumab maintenance treatment, the 12-month PFS rate was 87%; Darley Touximab + Melphalan + Bortezomib + Dexamethasone significantly reduced mortality and improved disease-free survival
.
Therefore, daratumomab is being explored as a highly effective and well-tolerated therapeutic target drug for myeloma
.
Adoptive cell transfer method and idiotypic vaccine: Phase I/II trials have shown that costimulatory T cell adoptive transfer mediated by tumor antigen vaccine can enhance the cellular and humoral immune response to the vaccine and the anti-tumor immunity of patients after ASCT; A phase II trial to explore anti-tumor-specific antigen vaccines is underway to extend the recurrence-free period of myeloma patients
.
Summary Lenalidomide or bortezomib is the standard care of maintenance treatment after prolonging PFS, potential OS and ASCT in patients with myeloma
.
The maintenance treatment plan depends on many factors, including previous treatment, the presence of high-risk characteristics, patient tolerance, and side effects
.
Long-term maintenance treatment can prolong PFS and delay the recurrence of the disease, but side effects need to be considered
.
In some patients, consolidation therapy can enhance the postoperative response of ASCT
.
References: 1.
Karam D, Kumar S.
Post-Transplant Maintenance Treatment Options in Multiple Myeloma.
Oncol Ther.
2021 Jun;9(1):69-88.
Stamp "read the original text", we make progress together
.
Friends who want to know the specific content, let us follow the editor and take a look! Research background Patients with myeloma still have a risk of recurrence after autologous stem cell transplantation (ASCT), and maintenance therapy after transplantation is needed to prolong the remission rate
.
After the initial diagnosis and risk stratification, the patient receives a multi-drug combination initial treatment, usually proteasome inhibitors and immunomodulatory drugs (IMiD), suitable for transplant patients to receive high-dose chemotherapy, and then autologous stem cell transplantation
.
The purpose of the research is to retrieve relevant literature, analyze and verify different maintenance treatment options after stem cell transplantation in patients with myeloma
.
Research methods: PubMed, the Cochrane Library, and the Evidence-Based Medicine Database (EBMR) were used to retrieve literature published between 2000 and 2009, as well as abstracts from American Society of Hematology/American Society of Clinical Oncology (ASH/ASCO) meetings and ongoing clinical trials
.
Article types include: Phase II, Phase III, and Phase IV clinical trials, randomized controlled trials (RTCs), retrospective/prospective studies, conference abstracts, and meta-analysis
.
A preliminary search of 110 articles on the use of maintenance therapy in adult patients with multiple myeloma was conducted.
After preliminary review, 55 abstracts/manuscripts were included for further analysis (Figure 1)
.
This article is based on previous research and does not include any new research on humans or animals
.
The results of the study in the late 1970s, the use of chemotherapy drugs as maintenance treatment did not prolong the survival of patients
.
In 1988, a randomized trial comparing the effectiveness of melphalan combined with prednisone maintenance treatment and non-maintenance treatment for MM patients showed that patients in the non-maintenance treatment group relapsed earlier, and the patients were treated with melphalan plus prednisone There is still a response, but it has no effect on OS; because the combination of melphalan will increase the toxicity, the use of melphalan-based maintenance therapy has not been applied to the clinic
.
Interferon: Some studies have shown that interferon α-2b maintenance treatment can enhance response and improve survival; but some studies have shown that interferon brings significant adverse effects; two landmark meta-analysis shows that interferon brings small survival benefits at the same time Accompanied by huge toxicity, it significantly affects the quality of life of patients
.
Therefore, the use of interferon for maintenance therapy is not recommended
.
Thalidomide: Two large-scale RCT studies in 2006, induction therapy and maintenance therapy with thalidomide after ASCT, showed that maintenance therapy with thalidomide can improve event-free survival and OS
.
In the HOVON-50 randomized phase III trial, compared with interferon, thalidomide maintenance treatment significantly prolonged PFS and improved OS; however, long-term follow-up results found that thalidomide maintenance treatment prolonged event-free survival compared with the control group.
Significantly toxic
.
Based on the limited access to IMiDs and proteasome inhibitors in developing countries, thalidomide can still be used as one of the maintenance treatment options after ASCT in these countries
.
Lenalidomide: In February 2017, the FDA approved lenalidomide for the maintenance treatment of MM patients after ASCT.
Common side effects are hematological adverse events such as cytopenia
.
It is recommended that a single ASCT and lenalidomide maintenance treatment be used as the standard care for patients receiving lenalidomide + bortezomib + dexamethasone (VRD) induction therapy
.
Currently, lenalidomide is an option for maintenance treatment after ASCT
.
Proteasome inhibitor: Bortezomib HOVON-65/GMMG-HD4 test showed that ASCT and bortezomib maintenance treatment after PAD (bortezomib, doxorubicin, dexamethasone) induction therapy can significantly prolong PFS and OS ; High-risk subgroup patients (nephropathy patients with chromosome 17p13 deletion and serum creatinine value exceeding 2 mg/dl) also have survival benefits
.
Therefore, bortezomib is a potential maintenance treatment option for prolonging PFS after ASCT, especially in high-risk patients
.
Ixazomib is administered orally once a week and can be used for the maintenance treatment of bortezomib-resistant and high-risk myeloma patients
.
The TOURMALINE-MM3 phase III trial showed that the induction treatment of newly diagnosed myeloma patients and the maintenance treatment of ixazomib after ASCT significantly prolonged PFS compared with the placebo group, which were 30.
7 months and 24.
9 months, respectively; the incidence of grade 3 adverse events was low (infection , Neutropenia, thrombocytopenia, peripheral neuropathy)
.
Ixazomib has good tolerability, convenient administration, low incidence of second malignant tumors, and significantly improves PFS.
It is a valuable maintenance option after ASCT
.
As a second-generation proteasome inhibitor, Carfilzomib has excellent efficacy
.
A phase I/II study showed that carfilzomib + lenalidomide + low-dose dexamethasone (CRd) is well tolerated and prolonged PFS after induction and maintenance therapy; another phase I/II study It has been shown that the use of carfilzomib + melphalan, ASCT and carfilzomib maintenance treatment in patients with recurrent myeloma brings PFS and OS benefits
.
Monoclonal antibodies: The anti-SLAMF7 antibody Errotuzumab and the anti-CD38 antibody Daratumumab were approved by the FDA for the treatment of myeloma patients in 2015
.
Erotuzumab + lenalidomide has satisfactory results and is well tolerated; Daratumumab as a first-line induction therapy can improve the remission rate and the depth of response without affecting the percentage of stem cell collection; LYRA research shows , Newly diagnosed and relapsed MM patients with daretuzumab + bortezomib + cyclophosphamide + dexamethasone induction therapy, ASCT and daretuzumab maintenance treatment, the 12-month PFS rate was 87%; Darley Touximab + Melphalan + Bortezomib + Dexamethasone significantly reduced mortality and improved disease-free survival
.
Therefore, daratumomab is being explored as a highly effective and well-tolerated therapeutic target drug for myeloma
.
Adoptive cell transfer method and idiotypic vaccine: Phase I/II trials have shown that costimulatory T cell adoptive transfer mediated by tumor antigen vaccine can enhance the cellular and humoral immune response to the vaccine and the anti-tumor immunity of patients after ASCT; A phase II trial to explore anti-tumor-specific antigen vaccines is underway to extend the recurrence-free period of myeloma patients
.
Summary Lenalidomide or bortezomib is the standard care of maintenance treatment after prolonging PFS, potential OS and ASCT in patients with myeloma
.
The maintenance treatment plan depends on many factors, including previous treatment, the presence of high-risk characteristics, patient tolerance, and side effects
.
Long-term maintenance treatment can prolong PFS and delay the recurrence of the disease, but side effects need to be considered
.
In some patients, consolidation therapy can enhance the postoperative response of ASCT
.
References: 1.
Karam D, Kumar S.
Post-Transplant Maintenance Treatment Options in Multiple Myeloma.
Oncol Ther.
2021 Jun;9(1):69-88.
Stamp "read the original text", we make progress together
