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Multiple myeloma (MM) is the second most common hematological malignancy with high heterogenei.
With the continuous advent of new drugs and the innovation of treatment methods, the diagnosis and treatment of MM has been gradually improved and perfected, but MM is still incurab.
High dependence on the microenvironment is a prominent feature of .
Accumulating evidence suggests that the immunosuppressive microenvironment can provide a sanctuary for MM cells and promote MM progressi.
While the stromal cells of the tumor protect the stem cells of the tumor, they form an immunosuppressive microenvironment, so that the minimal residual disease (MRD) cannot be eliminated, resulting in recurren.
As the number of recurrences increases, the difficulty of treatment also increases, so the choice of treatment options for patients with the first recurrence is very importa.
In this micro-classroom, Pr.
Wang Chong from the First Affiliated Hospital of Zhengzhou University is invited to share the immune microenvironment of multiple myeloma and the treatment of the first relapsed .
MM is a tumor that is highly dependent on the immune microenvironment, and the interaction between myeloma cells and the bone marrow microenvironment is crucial for the occurrence, development and treatment of myeloma disea.
Various factors secreted by hematopoietic cells such as osteoclasts and non-hematopoietic cells such as bone marrow stromal cells (BMSCs) and osteoblasts in the immune microenvironment of myeloma can promote the migration and proliferation of MM cells, and at the same time promote bone dama.
MM cells can generate an immunosuppressive local microenvironment, thereby helping MM cells to escape from the immune syst.
CD38 is an extracellular enzyme that is highly expressed on the surface of MM cells, as well as on osteoclast precursors and osteoclasts, and is closely related to the MM microenvironme.
It can promote the production of the immunosuppressive factor adenosine, resulting in immunosuppression of the MM microenvironment, and can also promote osteoclastogenesis, which is involved in MM immune esca.
CD38 is highly expressed in MM and also plays an important immunosuppressive role in the MM microenvironme.
There is no cure for MM, and the treatment of patients with late-line recurrence faces greater challeng.
Because with the increase of the number of relapses, the remission time will gradually shorten, and the patient may develop extramedullary lesio.
Therefore, the choice of treatment regimen for patients with first relapse is very importa.
The "Guidelines for the Diagnosis and Treatment of Multiple Myeloma in China (Revised 2022)" and "Management of multiple myeloma in the relapsed/refractory patient" published in Hematology both emphasize that the treatment goal for patients with first relapse is to obtain the deepest remission and prolong the progression-free survival of the disea.
Multiple factors should be considered when choosing a treatment plan for patients with relapsed MM:Disease-related factors: ISS stage at relapse, high-risk cytogenetic factors: t(4;14), del(17p), t(14;16), e.
Patient-related factors: age, comorbidities, functional status ( ECOG) or frailty index, e.
;Treatment-related factors: whether they have received HDT/ASCT treatment, whether they have received bortezomib/lenalidomide treatment in the past, whether they are resistant to bortezomib/lenalidomide, and whether they have received previous treatment The number of lines, the toxicity of previous treatment (bone marrow toxicity, peripheral neuropathy, thromboembolic events), the mode of administration (oral, intravenous or subcutaneous), e.
;The direction of future treatment optio.
In order to achieve the above treatment goals and comprehensively consider the above factors, domestic and foreign guidelines 1-4 recommend that the treatment regimens for patients with first relapse MM include daratumumab-based (Dara-base) regimens, including: DRd, DVd, DKd, DPd (Figure Figure 1 Domestic and foreign guidelines recommend the treatment regimen for patients with first relapsed .
Daratumumab is the world's first CD38 monoclonal antibody approved for the treatment of .
It has achieved good efficacy and safety in the treatment of patients with first relapsed .
The studies POLLUX and CASTOR demonstrated a survival benefit in patients with first relapsed MM5,The POLLUX study showed that patients with first relapse received Dara-containing regimens with significant benefits in depth of remission and P.
POLLUX is a multicenter, randomized, open-label Phase III clinical study of Dara combined with Rd regimen for relapsed or refractory multiple myeloma (RRMM), including a total of 569 patients with RR.
The data with a follow-up of 43 months showed that in the subgroup of patients with first relapse, the ≥CR rate in the DRd group was significantly higher than that in the Rd group (59% vs 29%, P=0003), and the MRD negative rate in the DRd group was also significantly higher than that in the Rd group ( 20% vs 3%, P < 000005), the DRd group significantly improved PFS compared with the Rd group, and the median PFS was 53 months vs 16 months, respectively (P < 0001) (Figure
Figure 2 POLLUX study cohort remission rate, MRD negative rate and median PFSCASTOR study also showed that the DVd group significantly reduced the risk of disease progression or death and improved PFS compared with the Vd group in the first relapse patien.
CASTOR is a multi-center, randomized, open-label Phase III clinical study of Dara combined with Vd regimen for RR.
A total of 498 patients with RRMM were includ.
The median follow-up data of the 2019 ASH meeting updated 52 mont.
In the subgroup, the MRD negative rate in the DVd group was significantly higher than that in the Vd group (21% vs 3%, P=000013), the DVd group reduced the risk of disease progression or death by 79% compared with the Vd group, and the DVd group significantly improved PFS compared with the Vd gro.
PFS was 27 months vs 9 months, respectively (P<0001), and the 48-month PFS rates were 32% vs 0%, respectively (Figure Figure 3 MRD-negative rate and median PFS in the CASTOR study The above two studies both showed that the MRD-negative rate and median PFS were higher in the first relapsed MM patients treated with the Dara-base regim.
A real-world retrospective analysis showed that the more Dara-containing regimens were applied at the frontline, the higher the remission rateA retrospective study that analyzed the clinical outcomes of 299 MM patients who started Dara treatment in the real world across different treatment lines from two clinical trial sites in the United States from 20111 to 20203 showed that 1 L, 2 L and 3 L + use of Dara The ORRs of patients with 100% were 100%, 78% and 62%, respectively, which also suggested that the more the Dara-containing regimen was applied in the frontline, the higher the remission rate (Figure
FigureReal-World Clinical Outcomes of MM Patients Initiating Dara at Different Lines Another retrospective study also showed that patients who were less resistant to prior therapy had greater benefit from Dara regimen A single-center retrospective clinical study involving 156 patients treated with Dara showed that the PFS survival curves of patients without relapse, first or second relapse, and triple relapse showed significant differences, with a median PFS of not reaching , 14 months, and 2 months (P<001), suggesting that patients with fewer drug resistances received greater benefit from Dara treatment (Figure
Figure 5 Summary of the PFS survival curve of patients who started Dara treatment at different lines in a retrospective clinical study and promote osteoclastogenes.
The treatment goal of the first relapse of multiple myeloma is the deepest remission and long-term progression-free survival, and the timing of the first treatment is very critic.
Two studies of POLLUX and CASTOR showed that in the first relapse subgroup, the Dara-base regimen had significant benefits in the depth of remission and PFS compared with the control group
Domestic and foreign guidelines for the treatment of patients with first relapsed MM recommend the Dara-base regim.
Real-world data show that the more front-line Dara is applied, the greater the benef.
END References [1] Harousseau JL, Attal.
How I treat first relapse of myelo.
Blo.
2017 Aug 24;130(8):963-97 [2] Dimopoulos MA, Moreau P, Terpos E, et .
Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-u.
Ann Onc.
2021 Mar;32(3):309-32[3] NCCN Clinical Practice Guidelines in multiple myeloma,2022 v[4 ] Moreau P, Kumar SK, San Miguel J, et .
Treatment of relapsed and refractory multiple myeloma: recommendations from the International Myeloma Working Gro.
Lancet Onc.
2021 Mar;22(3):e105-e11 [5] Kaufman JL , Usmani SZ, San-Miguel J , et .
Four-Year Follow-up of the Phase 3 Pollux Study of Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) Alone in Relapsed or Refractory Multiple Myeloma ( RRM.
Blood (2019) 134 (Supplement_1): 186 [6] Weisel KC,Sonneveld P, Mateos MV, et .
Efficacy and Safety of Daratumumab, Bortezomib, and Dexamethasone (D-Vd) Versus Bortezomib and Dexamethasone (Vd) in First Relapse Patients (pts) with Multiple Myeloma (MM): Four-Year Update of Cast.
Blood (2019) 134 (Supplement_1): 319 [7] Atrash S, Thompson-Leduc P, Tai MH, et .
Treatment patterns and effectiveness of patients with multiple myeloma initiating Daratumumab across different lines of therapy: a real- world chart review stu.
BMC Canc.
2021 Nov 12;21(1):120[8] Afram G, Gran C, Borg Bruchfeld J, et .
Impact of performance status on overall survival in patients with relapsed and/or refractory multiple myeloma: Real-life outcomes of daratumumab treatme.
Eur J Haemat.
2020 Aug;105(2):196-20MED-ONC-CN-2948 Content Approved Date: 5/11/2022 Edited: May Review: Moon typography: Youshi Execution: Wenting pokes "read the original text", let's make progress togetherMED-ONC-CN-2948 Content Approved Date: 5/11/2022 Edit: May Review: Moon Typesetting: Youshi Execution: Wenting Stamp "read the original text", we will progress together
With the continuous advent of new drugs and the innovation of treatment methods, the diagnosis and treatment of MM has been gradually improved and perfected, but MM is still incurab.
High dependence on the microenvironment is a prominent feature of .
Accumulating evidence suggests that the immunosuppressive microenvironment can provide a sanctuary for MM cells and promote MM progressi.
While the stromal cells of the tumor protect the stem cells of the tumor, they form an immunosuppressive microenvironment, so that the minimal residual disease (MRD) cannot be eliminated, resulting in recurren.
As the number of recurrences increases, the difficulty of treatment also increases, so the choice of treatment options for patients with the first recurrence is very importa.
In this micro-classroom, Pr.
Wang Chong from the First Affiliated Hospital of Zhengzhou University is invited to share the immune microenvironment of multiple myeloma and the treatment of the first relapsed .
MM is a tumor that is highly dependent on the immune microenvironment, and the interaction between myeloma cells and the bone marrow microenvironment is crucial for the occurrence, development and treatment of myeloma disea.
Various factors secreted by hematopoietic cells such as osteoclasts and non-hematopoietic cells such as bone marrow stromal cells (BMSCs) and osteoblasts in the immune microenvironment of myeloma can promote the migration and proliferation of MM cells, and at the same time promote bone dama.
MM cells can generate an immunosuppressive local microenvironment, thereby helping MM cells to escape from the immune syst.
CD38 is an extracellular enzyme that is highly expressed on the surface of MM cells, as well as on osteoclast precursors and osteoclasts, and is closely related to the MM microenvironme.
It can promote the production of the immunosuppressive factor adenosine, resulting in immunosuppression of the MM microenvironment, and can also promote osteoclastogenesis, which is involved in MM immune esca.
CD38 is highly expressed in MM and also plays an important immunosuppressive role in the MM microenvironme.
There is no cure for MM, and the treatment of patients with late-line recurrence faces greater challeng.
Because with the increase of the number of relapses, the remission time will gradually shorten, and the patient may develop extramedullary lesio.
Therefore, the choice of treatment regimen for patients with first relapse is very importa.
The "Guidelines for the Diagnosis and Treatment of Multiple Myeloma in China (Revised 2022)" and "Management of multiple myeloma in the relapsed/refractory patient" published in Hematology both emphasize that the treatment goal for patients with first relapse is to obtain the deepest remission and prolong the progression-free survival of the disea.
Multiple factors should be considered when choosing a treatment plan for patients with relapsed MM:Disease-related factors: ISS stage at relapse, high-risk cytogenetic factors: t(4;14), del(17p), t(14;16), e.
Patient-related factors: age, comorbidities, functional status ( ECOG) or frailty index, e.
;Treatment-related factors: whether they have received HDT/ASCT treatment, whether they have received bortezomib/lenalidomide treatment in the past, whether they are resistant to bortezomib/lenalidomide, and whether they have received previous treatment The number of lines, the toxicity of previous treatment (bone marrow toxicity, peripheral neuropathy, thromboembolic events), the mode of administration (oral, intravenous or subcutaneous), e.
;The direction of future treatment optio.
In order to achieve the above treatment goals and comprehensively consider the above factors, domestic and foreign guidelines 1-4 recommend that the treatment regimens for patients with first relapse MM include daratumumab-based (Dara-base) regimens, including: DRd, DVd, DKd, DPd (Figure Figure 1 Domestic and foreign guidelines recommend the treatment regimen for patients with first relapsed .
Daratumumab is the world's first CD38 monoclonal antibody approved for the treatment of .
It has achieved good efficacy and safety in the treatment of patients with first relapsed .
The studies POLLUX and CASTOR demonstrated a survival benefit in patients with first relapsed MM5,The POLLUX study showed that patients with first relapse received Dara-containing regimens with significant benefits in depth of remission and P.
POLLUX is a multicenter, randomized, open-label Phase III clinical study of Dara combined with Rd regimen for relapsed or refractory multiple myeloma (RRMM), including a total of 569 patients with RR.
The data with a follow-up of 43 months showed that in the subgroup of patients with first relapse, the ≥CR rate in the DRd group was significantly higher than that in the Rd group (59% vs 29%, P=0003), and the MRD negative rate in the DRd group was also significantly higher than that in the Rd group ( 20% vs 3%, P < 000005), the DRd group significantly improved PFS compared with the Rd group, and the median PFS was 53 months vs 16 months, respectively (P < 0001) (Figure
Figure 2 POLLUX study cohort remission rate, MRD negative rate and median PFSCASTOR study also showed that the DVd group significantly reduced the risk of disease progression or death and improved PFS compared with the Vd group in the first relapse patien.
CASTOR is a multi-center, randomized, open-label Phase III clinical study of Dara combined with Vd regimen for RR.
A total of 498 patients with RRMM were includ.
The median follow-up data of the 2019 ASH meeting updated 52 mont.
In the subgroup, the MRD negative rate in the DVd group was significantly higher than that in the Vd group (21% vs 3%, P=000013), the DVd group reduced the risk of disease progression or death by 79% compared with the Vd group, and the DVd group significantly improved PFS compared with the Vd gro.
PFS was 27 months vs 9 months, respectively (P<0001), and the 48-month PFS rates were 32% vs 0%, respectively (Figure Figure 3 MRD-negative rate and median PFS in the CASTOR study The above two studies both showed that the MRD-negative rate and median PFS were higher in the first relapsed MM patients treated with the Dara-base regim.
A real-world retrospective analysis showed that the more Dara-containing regimens were applied at the frontline, the higher the remission rateA retrospective study that analyzed the clinical outcomes of 299 MM patients who started Dara treatment in the real world across different treatment lines from two clinical trial sites in the United States from 20111 to 20203 showed that 1 L, 2 L and 3 L + use of Dara The ORRs of patients with 100% were 100%, 78% and 62%, respectively, which also suggested that the more the Dara-containing regimen was applied in the frontline, the higher the remission rate (Figure
FigureReal-World Clinical Outcomes of MM Patients Initiating Dara at Different Lines Another retrospective study also showed that patients who were less resistant to prior therapy had greater benefit from Dara regimen A single-center retrospective clinical study involving 156 patients treated with Dara showed that the PFS survival curves of patients without relapse, first or second relapse, and triple relapse showed significant differences, with a median PFS of not reaching , 14 months, and 2 months (P<001), suggesting that patients with fewer drug resistances received greater benefit from Dara treatment (Figure
Figure 5 Summary of the PFS survival curve of patients who started Dara treatment at different lines in a retrospective clinical study and promote osteoclastogenes.
The treatment goal of the first relapse of multiple myeloma is the deepest remission and long-term progression-free survival, and the timing of the first treatment is very critic.
Two studies of POLLUX and CASTOR showed that in the first relapse subgroup, the Dara-base regimen had significant benefits in the depth of remission and PFS compared with the control group
Domestic and foreign guidelines for the treatment of patients with first relapsed MM recommend the Dara-base regim.
Real-world data show that the more front-line Dara is applied, the greater the benef.
END References [1] Harousseau JL, Attal.
How I treat first relapse of myelo.
Blo.
2017 Aug 24;130(8):963-97 [2] Dimopoulos MA, Moreau P, Terpos E, et .
Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-u.
Ann Onc.
2021 Mar;32(3):309-32[3] NCCN Clinical Practice Guidelines in multiple myeloma,2022 v[4 ] Moreau P, Kumar SK, San Miguel J, et .
Treatment of relapsed and refractory multiple myeloma: recommendations from the International Myeloma Working Gro.
Lancet Onc.
2021 Mar;22(3):e105-e11 [5] Kaufman JL , Usmani SZ, San-Miguel J , et .
Four-Year Follow-up of the Phase 3 Pollux Study of Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) Alone in Relapsed or Refractory Multiple Myeloma ( RRM.
Blood (2019) 134 (Supplement_1): 186 [6] Weisel KC,Sonneveld P, Mateos MV, et .
Efficacy and Safety of Daratumumab, Bortezomib, and Dexamethasone (D-Vd) Versus Bortezomib and Dexamethasone (Vd) in First Relapse Patients (pts) with Multiple Myeloma (MM): Four-Year Update of Cast.
Blood (2019) 134 (Supplement_1): 319 [7] Atrash S, Thompson-Leduc P, Tai MH, et .
Treatment patterns and effectiveness of patients with multiple myeloma initiating Daratumumab across different lines of therapy: a real- world chart review stu.
BMC Canc.
2021 Nov 12;21(1):120[8] Afram G, Gran C, Borg Bruchfeld J, et .
Impact of performance status on overall survival in patients with relapsed and/or refractory multiple myeloma: Real-life outcomes of daratumumab treatme.
Eur J Haemat.
2020 Aug;105(2):196-20MED-ONC-CN-2948 Content Approved Date: 5/11/2022 Edited: May Review: Moon typography: Youshi Execution: Wenting pokes "read the original text", let's make progress togetherMED-ONC-CN-2948 Content Approved Date: 5/11/2022 Edit: May Review: Moon Typesetting: Youshi Execution: Wenting Stamp "read the original text", we will progress together
