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Although the treatment of MM has progressed in recent years, almost all patients with MM eventually relapse, and the difficulty of treatment is gradually increasing
.
Therefore, there is an urgent need for treatments that provide deep and durable remission, prolong time to disease progression or death, and have no substantial negative impact on health-related quality of life
.
The introduction of daratumumab, a monoclonal antibody targeting CD38, has further improved the efficacy and prognosis of MM patients
.
Results from Part 1 of the classic CASSIOPEIA trial showed daratumumab in combination with bortezomib, thalidomide, and dexamethasone in patients with newly diagnosed MM (NDMM) eligible for autologous hematopoietic stem cell transplantation (ASCT).
Compared with patients receiving VTd, the patients receiving metasone (D-VTd) as an induction and consolidation regimen had better depth of remission and significantly improved progression-free survival (PFS)
.
Based on the results of Part 1 of the CASSIOPEIA study, D-VTd has been approved in regions and countries around the world, including the U.
S.
Food and Drug Administration (FDA) and the European Medicines Agency (EMA), as a treatment for transplant-appropriate NDMM patients
.
To prolong response to first-line therapy, long-term maintenance therapy may be given
.
Some researchers have reported the results of the second part of the CASSIOPEIA trial, let's take a look
.
Research Methods The CASSIOPEIA study was an open-label, randomized, phase III clinical study conducted at 111 European academic and community centers
.
Patients were randomly assigned (1:1) to D-VTd or VTd in part 1 of the study and received daratumumab maintenance therapy or observation in part 2
.
In Part 1, patients received 4 cycles of D-VTd or VTd induction therapy and 2 cycles of consolidation therapy
.
After randomization to Part 2, patients were assigned to receive 16 mg/kg of daratumumab intravenously every 8 weeks or observation only for up to 2 years
.
The primary endpoint of Part 2 was progression-free survival (PFS) after the second randomization; the primary secondary efficacy endpoint of Part 2 was the time from second randomization to disease progression, ≥complete by IMWG criteria Proportion of patients in response (CR), proportion of patients negative for minimal residual disease (MRD) according to next-generation sequencing (10-5), PFS after next-line therapy, overall response rate (ORR) and overall response rate after second randomization Lifetime (OS)
.
RESULTS: Study process and patient characteristics Between May 30, 2016, and June 18, 2018, 886 patients with ≥ partial response (PR) in Part 1 were randomly assigned to daratumumab maintenance therapy ( 442 cases) or observation group (444 cases) (Figure 1)
.
373 (84%) of 442 patients in the daratumumab maintenance group and 391 (88%) of 444 patients in the observation group were from the IFM center
.
Sixty-nine patients (16%) in the daratumumab maintenance group and 53 (12%) in the observation group were from the HOVON Research Center
.
A second randomization was performed in 458 of 543 patients (84%) in the D-VTd group and 428 of 542 (79%) in the VTd group
.
Of the 199 patients who were not randomized to Part 2, the most common cause was adverse events (AEs), followed by disease progression during induction, ASCT, or consolidation, and remission of stable or worsening disease after consolidation
.
Demographics and disease characteristics after the second randomization are shown in Table 1
.
Figure 1: Study Flow Chart Table 1: Maintenance Treatment Pre-Maintenance Baseline Demographics and Disease Characteristics in the Specific Intent-to-Treat Population Efficacy Median duration of treatment during the maintenance treatment period was 24.
0 months in the daratumumab group and 24.
0 months in the observation group 22.
2 months
.
In a preplanned interim analysis, after a median follow-up of 35.
4 months after the second randomization, median PFS was not reached in the daratumumab group compared with 46.
7 months in the observation group (HR 0.
53, 95% CI 0.
42-0.
68, P < 0.
0001; Figure 2)
.
The PFS of the pre-specified subgroups is shown in Figure 3
.
Compared with the observation group, the daratumumab maintenance group had higher ≥CR rate (p<0.
0001) and MRD negative rate (p=0.
0001)
.
Median OS was not reached in either group
.
A prespecified interaction analysis of progression-free survival showed a significant interaction between maintenance, induction, and consolidation therapy (p<0.
0001)
.
Figure 2: Kaplan-Meier estimates of PFS for patients in the maintenance-specific intention-to-treat population Figure 3: The median PFS in the PFSVTd-combined observation group in the pre-specified subgroup in the maintenance-specific intention-to-treat population was 33.
6 months (95% CI 27.
2 –37.
4)
.
D-VTd combined with daratumumab maintenance therapy group, D-VTd combined with observation group or VTd combined with daratumumab maintenance therapy group did not reach the median PFS
.
The PFS benefit in the VTd plus daratumumab group was greater than that in the VTd plus observation group (HR 0.
32; nominal p<0.
0001)
.
There was no significant difference in PFS between the D-VTd combined with daratumumab group and the D-VTd combined observation group
.
The latest analysis comparing D-VTd to VTd confirmed the results of the primary analysis in Part 1, that the median follow-up time between the D-VTd group and the VTd group was 44.
5 months; the PFS in the D-VTd group was sustained compared with the VTd group Significant improvement (median PFS not reached vs 51.
5 months) (p < 0.
0001)
.
Median OS was not reached in either group
.
Safety "On-treatment" AEs occurred in 420 (95%) of 440 patients in the daratumumab group and in 394 (89%) of 444 patients in the observation group
.
Serious adverse events (SAEs) occurred in 23% of patients in the daratumumab group and 19% in the observation group; 32% of SAEs in the daratumumab group were drug-related
.
The SAE that occurred in more than 1% of patients in the daratumumab or observation group was pneumonitis
.
Daratumumab infusions were interrupted by AEs in 21% of patients, and infusion-related reactions occurred in all but 1 patient
.
CONCLUSIONS: Compared with observation, maintenance daratumumab every 8 weeks for 2 years significantly reduced the risk of disease progression or death in transplant-eligible NDMM
.
Longer follow-up and other ongoing studies will further clarify whether daratumumab is the optimal maintenance strategy for ASCT
.
References Philippe Moreau, Cyrille Hulin, Aurore Perrot, et al.
Maintenance with daratumumab or observation following treatment with bortezomib, thalidomide, and dexamethasone with or without daratumumab and autologous stem-cell transplant in patients with newly diagnosed multiple myeloma (CASSIOPEIA): an open-label, randomised, phase 3 trial.
Lancet Oncol.
2021 Sep 13;S1470-2045(21)00428-9.
Click "read the original text", we will make progress together
.
Therefore, there is an urgent need for treatments that provide deep and durable remission, prolong time to disease progression or death, and have no substantial negative impact on health-related quality of life
.
The introduction of daratumumab, a monoclonal antibody targeting CD38, has further improved the efficacy and prognosis of MM patients
.
Results from Part 1 of the classic CASSIOPEIA trial showed daratumumab in combination with bortezomib, thalidomide, and dexamethasone in patients with newly diagnosed MM (NDMM) eligible for autologous hematopoietic stem cell transplantation (ASCT).
Compared with patients receiving VTd, the patients receiving metasone (D-VTd) as an induction and consolidation regimen had better depth of remission and significantly improved progression-free survival (PFS)
.
Based on the results of Part 1 of the CASSIOPEIA study, D-VTd has been approved in regions and countries around the world, including the U.
S.
Food and Drug Administration (FDA) and the European Medicines Agency (EMA), as a treatment for transplant-appropriate NDMM patients
.
To prolong response to first-line therapy, long-term maintenance therapy may be given
.
Some researchers have reported the results of the second part of the CASSIOPEIA trial, let's take a look
.
Research Methods The CASSIOPEIA study was an open-label, randomized, phase III clinical study conducted at 111 European academic and community centers
.
Patients were randomly assigned (1:1) to D-VTd or VTd in part 1 of the study and received daratumumab maintenance therapy or observation in part 2
.
In Part 1, patients received 4 cycles of D-VTd or VTd induction therapy and 2 cycles of consolidation therapy
.
After randomization to Part 2, patients were assigned to receive 16 mg/kg of daratumumab intravenously every 8 weeks or observation only for up to 2 years
.
The primary endpoint of Part 2 was progression-free survival (PFS) after the second randomization; the primary secondary efficacy endpoint of Part 2 was the time from second randomization to disease progression, ≥complete by IMWG criteria Proportion of patients in response (CR), proportion of patients negative for minimal residual disease (MRD) according to next-generation sequencing (10-5), PFS after next-line therapy, overall response rate (ORR) and overall response rate after second randomization Lifetime (OS)
.
RESULTS: Study process and patient characteristics Between May 30, 2016, and June 18, 2018, 886 patients with ≥ partial response (PR) in Part 1 were randomly assigned to daratumumab maintenance therapy ( 442 cases) or observation group (444 cases) (Figure 1)
.
373 (84%) of 442 patients in the daratumumab maintenance group and 391 (88%) of 444 patients in the observation group were from the IFM center
.
Sixty-nine patients (16%) in the daratumumab maintenance group and 53 (12%) in the observation group were from the HOVON Research Center
.
A second randomization was performed in 458 of 543 patients (84%) in the D-VTd group and 428 of 542 (79%) in the VTd group
.
Of the 199 patients who were not randomized to Part 2, the most common cause was adverse events (AEs), followed by disease progression during induction, ASCT, or consolidation, and remission of stable or worsening disease after consolidation
.
Demographics and disease characteristics after the second randomization are shown in Table 1
.
Figure 1: Study Flow Chart Table 1: Maintenance Treatment Pre-Maintenance Baseline Demographics and Disease Characteristics in the Specific Intent-to-Treat Population Efficacy Median duration of treatment during the maintenance treatment period was 24.
0 months in the daratumumab group and 24.
0 months in the observation group 22.
2 months
.
In a preplanned interim analysis, after a median follow-up of 35.
4 months after the second randomization, median PFS was not reached in the daratumumab group compared with 46.
7 months in the observation group (HR 0.
53, 95% CI 0.
42-0.
68, P < 0.
0001; Figure 2)
.
The PFS of the pre-specified subgroups is shown in Figure 3
.
Compared with the observation group, the daratumumab maintenance group had higher ≥CR rate (p<0.
0001) and MRD negative rate (p=0.
0001)
.
Median OS was not reached in either group
.
A prespecified interaction analysis of progression-free survival showed a significant interaction between maintenance, induction, and consolidation therapy (p<0.
0001)
.
Figure 2: Kaplan-Meier estimates of PFS for patients in the maintenance-specific intention-to-treat population Figure 3: The median PFS in the PFSVTd-combined observation group in the pre-specified subgroup in the maintenance-specific intention-to-treat population was 33.
6 months (95% CI 27.
2 –37.
4)
.
D-VTd combined with daratumumab maintenance therapy group, D-VTd combined with observation group or VTd combined with daratumumab maintenance therapy group did not reach the median PFS
.
The PFS benefit in the VTd plus daratumumab group was greater than that in the VTd plus observation group (HR 0.
32; nominal p<0.
0001)
.
There was no significant difference in PFS between the D-VTd combined with daratumumab group and the D-VTd combined observation group
.
The latest analysis comparing D-VTd to VTd confirmed the results of the primary analysis in Part 1, that the median follow-up time between the D-VTd group and the VTd group was 44.
5 months; the PFS in the D-VTd group was sustained compared with the VTd group Significant improvement (median PFS not reached vs 51.
5 months) (p < 0.
0001)
.
Median OS was not reached in either group
.
Safety "On-treatment" AEs occurred in 420 (95%) of 440 patients in the daratumumab group and in 394 (89%) of 444 patients in the observation group
.
Serious adverse events (SAEs) occurred in 23% of patients in the daratumumab group and 19% in the observation group; 32% of SAEs in the daratumumab group were drug-related
.
The SAE that occurred in more than 1% of patients in the daratumumab or observation group was pneumonitis
.
Daratumumab infusions were interrupted by AEs in 21% of patients, and infusion-related reactions occurred in all but 1 patient
.
CONCLUSIONS: Compared with observation, maintenance daratumumab every 8 weeks for 2 years significantly reduced the risk of disease progression or death in transplant-eligible NDMM
.
Longer follow-up and other ongoing studies will further clarify whether daratumumab is the optimal maintenance strategy for ASCT
.
References Philippe Moreau, Cyrille Hulin, Aurore Perrot, et al.
Maintenance with daratumumab or observation following treatment with bortezomib, thalidomide, and dexamethasone with or without daratumumab and autologous stem-cell transplant in patients with newly diagnosed multiple myeloma (CASSIOPEIA): an open-label, randomised, phase 3 trial.
Lancet Oncol.
2021 Sep 13;S1470-2045(21)00428-9.
Click "read the original text", we will make progress together
