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Professor Ola Landgren and others conducted a non-randomized clinical study, adding Darre to the KRd (carfilzomib, lenalidomide, and dexamethasone) three-drug regimen with the second-generation proteasome inhibitor as the backbone.
Toyuumab is designed to evaluate the efficacy and safety of the powerful combination of four-drug regimen D-KRd in newly diagnosed multiple myeloma (NDMM) patients.
Research background and purpose For NDMM, the standard treatment strategy recommended by the current clinical guidelines is: firstly give a multi-drug combination regimen for induction therapy, and determine whether to receive a pretreatment regimen of high-dose melphalan autologous stem cell transplantation (ASCT) based on the patient’s age and comorbidities.
), followed by maintenance treatment.
The results of a prospective, randomized, phase III clinical study showed that the first-generation proteasome inhibitor bortezomib, lenalidomide, and dexamethasone were induced by a three-drug regimen (VRd) combined with ASCT in NDMM, and the median progression-free survival The period (PFS) is up to 50 months.
Daratumumab is a humanized anti-immunoglobulin Gκ (IgGκ) monoclonal antibody that targets CD38.
The results of randomized phase III clinical studies have shown that adding daratumumab to the original three-drug regimen has a higher level of minimal residual disease (MRD) negativity in both NDMM and relapsed/refractory MM (RRMM).
Rate, which translates to a longer median PFS.
GRIFFIN test results show that ASCT treatment of NDMM patients after D-VRd induction therapy has a higher MRD negative rate.
Based on the above content, the researchers carried out the MANHATTAN study to evaluate the efficacy and safety of the D-KRd regimen in the treatment of NDMM patients.
Research methods The MANHATTAN study is a single-center, phase II non-randomized clinical study initiated by researchers at the Memorial Sloan Kettering Cancer Center (MSKCC) in New York.
The included patients were NDMM patients ≥18 years of age who were diagnosed by the International Multiple Myeloma Working Group (IMWG) criteria and had a physical status score of 0-2 by the Eastern Cooperative Oncology Group (ECOG).
All patients received 8 cycles of D-KRd treatment, specifically carfilzomib 20/56mg/m2, intravenous injection (days 1, 8 and 15); lenalidomide 25mg, oral (days 1-21); Dexamethasone 40mg, orally or intravenously, once a week (cycles 1-4), 20mg orally or intravenously, once a week (cycles 5-8); daratumumab 16mg/kg intravenously Injection, day 1, 8, 15 and 22 (cycles 1-2), day 1 and 15 (cycles 3-6), day 1 (cycles 7-8); day 28 is a treatment cycle .
The primary endpoint is the MRD negative rate of patients after 8 cycles of D-KRd regimen treatment.
Research results The trial enrolled 41 patients from October 1, 2018 to December 15, 2019, with a median age of 59 years (range 30-70 years), and 61% of male patients.
High-risk patients are defined as fluorescence in situ hybridization or single nucleotide mutants with one or more of the following abnormalities: 1q+, t(4;14), t(14;16), t(14;20) and/or 17p-; accounted for 49% of the study.
All patients completed the planned treatment, and the median follow-up time from treatment was 20.
3 months (95% CI: 19.
2-21.
9 months).
In this trial, the negative rate of bone marrow MRD of patients after 8 cycles of treatment was 71% (95% CI: 54%-83%), which reached the primary study endpoint.
The median time for patients to reach MRD negative is 6 cycles (range 1-8 cycles).
The patient’s overall response rate (ORR) and very good partial response (VGPR) or complete response (CR) rates were 100% and 95%, respectively; at a median follow-up of 11 months, the 1-year progression-free survival (PFS) rate And overall survival (OS) rates were 98% (95% CI: 93%-100%) and 100%, respectively.
In this trial, 40 patients underwent peripheral blood stem cell collection after 4 cycles of treatment, and continued to complete the remaining 4 cycles of treatment after the collection was completed.
The median absolute value of CD34+ cells in peripheral blood stem cells collected from patients was 8×106 cells/kg.
The most common (≥2 patients) grade 3 or 4 adverse events (AE) were neutropenia (27%), skin rash (9%), lung infection (7%) and elevated transaminase levels (4 %), no patients died.
One patient had a normal echocardiogram at baseline, but had evidence of coronary heart disease during treatment.
No patients had peripheral neuropathy of grade ≥3.
A total of 18 patients (40%) had daratumumab-related infusion reactions, but all of them were grade 2.
Eight patients (18%) had serious treatment-related AEs, the most common being lung infections (7%).
Research conclusions The results of this non-randomized clinical study show that the D-KRd regimen (not including ASCT) has an excellent MRD negative rate in NDMM patients.
Looking forward to follow-up randomized clinical studies to further confirm the effectiveness of the four-drug regimen in NDMM patients.
References: Ola Landgren, Malin Hultcrantz, Benjamin Diamond, et al.
Safety and Effectiveness of Weekly Carfilzomib, Lenalidomide, Dexamethasone, and Daratumumab Combination Therapy for Patients With Newly Diagnosed Multiple Myeloma: The MANHATTAN Nonrandomized Clinical Trial.
JAMA 15 Apr 2021 .
doi: 10.
1001/jamaoncol.
2021.
0611.
Online ahead of print.
Stamp "read the original text" and we will make progress together
Toyuumab is designed to evaluate the efficacy and safety of the powerful combination of four-drug regimen D-KRd in newly diagnosed multiple myeloma (NDMM) patients.
Research background and purpose For NDMM, the standard treatment strategy recommended by the current clinical guidelines is: firstly give a multi-drug combination regimen for induction therapy, and determine whether to receive a pretreatment regimen of high-dose melphalan autologous stem cell transplantation (ASCT) based on the patient’s age and comorbidities.
), followed by maintenance treatment.
The results of a prospective, randomized, phase III clinical study showed that the first-generation proteasome inhibitor bortezomib, lenalidomide, and dexamethasone were induced by a three-drug regimen (VRd) combined with ASCT in NDMM, and the median progression-free survival The period (PFS) is up to 50 months.
Daratumumab is a humanized anti-immunoglobulin Gκ (IgGκ) monoclonal antibody that targets CD38.
The results of randomized phase III clinical studies have shown that adding daratumumab to the original three-drug regimen has a higher level of minimal residual disease (MRD) negativity in both NDMM and relapsed/refractory MM (RRMM).
Rate, which translates to a longer median PFS.
GRIFFIN test results show that ASCT treatment of NDMM patients after D-VRd induction therapy has a higher MRD negative rate.
Based on the above content, the researchers carried out the MANHATTAN study to evaluate the efficacy and safety of the D-KRd regimen in the treatment of NDMM patients.
Research methods The MANHATTAN study is a single-center, phase II non-randomized clinical study initiated by researchers at the Memorial Sloan Kettering Cancer Center (MSKCC) in New York.
The included patients were NDMM patients ≥18 years of age who were diagnosed by the International Multiple Myeloma Working Group (IMWG) criteria and had a physical status score of 0-2 by the Eastern Cooperative Oncology Group (ECOG).
All patients received 8 cycles of D-KRd treatment, specifically carfilzomib 20/56mg/m2, intravenous injection (days 1, 8 and 15); lenalidomide 25mg, oral (days 1-21); Dexamethasone 40mg, orally or intravenously, once a week (cycles 1-4), 20mg orally or intravenously, once a week (cycles 5-8); daratumumab 16mg/kg intravenously Injection, day 1, 8, 15 and 22 (cycles 1-2), day 1 and 15 (cycles 3-6), day 1 (cycles 7-8); day 28 is a treatment cycle .
The primary endpoint is the MRD negative rate of patients after 8 cycles of D-KRd regimen treatment.
Research results The trial enrolled 41 patients from October 1, 2018 to December 15, 2019, with a median age of 59 years (range 30-70 years), and 61% of male patients.
High-risk patients are defined as fluorescence in situ hybridization or single nucleotide mutants with one or more of the following abnormalities: 1q+, t(4;14), t(14;16), t(14;20) and/or 17p-; accounted for 49% of the study.
All patients completed the planned treatment, and the median follow-up time from treatment was 20.
3 months (95% CI: 19.
2-21.
9 months).
In this trial, the negative rate of bone marrow MRD of patients after 8 cycles of treatment was 71% (95% CI: 54%-83%), which reached the primary study endpoint.
The median time for patients to reach MRD negative is 6 cycles (range 1-8 cycles).
The patient’s overall response rate (ORR) and very good partial response (VGPR) or complete response (CR) rates were 100% and 95%, respectively; at a median follow-up of 11 months, the 1-year progression-free survival (PFS) rate And overall survival (OS) rates were 98% (95% CI: 93%-100%) and 100%, respectively.
In this trial, 40 patients underwent peripheral blood stem cell collection after 4 cycles of treatment, and continued to complete the remaining 4 cycles of treatment after the collection was completed.
The median absolute value of CD34+ cells in peripheral blood stem cells collected from patients was 8×106 cells/kg.
The most common (≥2 patients) grade 3 or 4 adverse events (AE) were neutropenia (27%), skin rash (9%), lung infection (7%) and elevated transaminase levels (4 %), no patients died.
One patient had a normal echocardiogram at baseline, but had evidence of coronary heart disease during treatment.
No patients had peripheral neuropathy of grade ≥3.
A total of 18 patients (40%) had daratumumab-related infusion reactions, but all of them were grade 2.
Eight patients (18%) had serious treatment-related AEs, the most common being lung infections (7%).
Research conclusions The results of this non-randomized clinical study show that the D-KRd regimen (not including ASCT) has an excellent MRD negative rate in NDMM patients.
Looking forward to follow-up randomized clinical studies to further confirm the effectiveness of the four-drug regimen in NDMM patients.
References: Ola Landgren, Malin Hultcrantz, Benjamin Diamond, et al.
Safety and Effectiveness of Weekly Carfilzomib, Lenalidomide, Dexamethasone, and Daratumumab Combination Therapy for Patients With Newly Diagnosed Multiple Myeloma: The MANHATTAN Nonrandomized Clinical Trial.
JAMA 15 Apr 2021 .
doi: 10.
1001/jamaoncol.
2021.
0611.
Online ahead of print.
Stamp "read the original text" and we will make progress together
