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The current standard first-line treatment for multiple myeloma (MM) includes induction therapy with immunomodulators (IMiD), monoclonal antibodies (mAb) and proteasome inhibitors (PI).
Patients who are suitable for transplantation are subsequently treated with autologous hematopoietic stem cell transplantation (ASCT).
) Maintenance treatment is given after consolidation treatment
.
Although there are a variety of highly effective new drugs for MM, almost all patients will relapse and require follow-up treatment
.
MM cytogenetic abnormalities can affect clinical outcomes, accompanied by high-risk abnormalities in cytogenetics, such as del(17p), t(4;14), t(14;16) and 1q21 amplification, and accompanied by standard risk cytogenetics Compared with patients, they have shorter progression-free survival (PFS) and overall survival (OS)
.
Therefore, new treatment options are needed to overcome the poor prognosis of these patients with relapsed or refractory MM (R/R MM) accompanied by high-risk cytogenetic changes
.
Celinisol is a potent, oral, selective nuclear export inhibitor (SINE) compound
.
The BOSTON trial is a phase III clinical study.
The previous results showed that Celinisol combined with bortezomib and dexamethasone (XVd) significantly improved the overall survival rate (ORR) and The median PFS is associated with a lower incidence of peripheral neuropathy, and OS also tends to benefit
.
Based on this, some researchers analyzed whether combining Celinisol on the basis of Vd can improve the prognosis of patients with high-risk R/R MM
.
Research methods The BOSTON trial is an international, open-label, randomized, phase III clinical study
.
According to the International Myeloma Working Group (IMWG) criteria, patients aged ≥18 years, histologically confirmed MM, and previously received 1-3 systemic anti-MM regimens were included
.
The patients included in the study were randomly assigned (1:1) to the XVd or Vd group according to the previous PI treatment (yes or not), the number of previous anti-MM treatment regimens (1 vs 2-3) and the revised international staging system ( R-ISS; I-II vs III) to determine the disease stage for randomization and stratification
.
The primary endpoint was PFS assessed by the independent review committee, and the secondary endpoints included OS, ORR, duration of remission (DOR), time to next treatment (TTNT), incidence of peripheral neuropathy ≥2 and safety
.
Research results 1 Patient characteristics The BOSTON study included a total of 402 MM patients who had previously received 1-3 lines of treatment and received randomization, including 195 cases in the XVd group and 207 cases in the Vd group
.
Among them, 141 patients (35.
1%) had high-risk cytogenetic abnormalities, 70 patients in the XVd group and 71 patients in the Vd group; 261 (64.
9%) patients were standard risk cytogenetic MM, and the XVd group patients were 125, 136 patients in the Vd group
.
In the subgroups defined by cytogenetic risk, the baseline demographics and disease characteristics of patients were evenly distributed between the two treatment groups (see Table 1 for details)
.
Among patients in the two treatment groups, 1q21 amplification was the most common cytogenetic abnormality, with 22.
1% in the XVd group and 18.
8% in the Vd group
.
The proportion of men with high-risk cytogenetic characteristics is even lower
.
The bortezomib-containing regimen is the most commonly used previous treatment, followed by the lenalidomide-containing regimen
.
Table 1: Baseline characteristics of patients 2 Among patients with high-risk cytogenetic abnormalities in efficacy, patients treated with XVd had longer median PFS than Vd, which were 12.
91 months and 8.
61 months (HR 0.
73; 95%) CI, 0.
47-1.
14; one-sided p=0.
0827) (Figure 1)
.
Also in standard-risk cytogenetic patients, patients treated with XVd compared with Vd also had longer median PFS distributions of 16.
62 months and 9.
46 months (HR 0.
61; 95% CI, 0.
42–0.
88; unilateral p=0.
0036) (Figure 1)
.
Figure 1: Patients with different cytogenetic subgroups between the two treatment groups have high risk of PFS (78.
6% vs 57.
7%; unilateral p=0.
0041) and standard risk (75.
2% vs 64.
7%; p=0.
0329) subgroups, Patients treated with XVd had higher ORR than Vd (Table 2)
.
In addition, in the high-risk subgroup, the proportion of patients in the XVd group who achieved ≥Very good partial remission (VGPR) was also significantly higher than that in the Vd group (30.
0% vs 18.
3%)
.
Patients in the standard-risk and high-risk groups who received XVd had a lower disease progression (PD) rate than those treated with Vd
.
In addition, in the high-risk (14.
03 vs 8.
61 months; one-sided p = 0.
0178) and standard risk (18.
23 vs 11.
73 months; one-sided p = 0.
0178) subgroups, patients who received XVd were significantly longer than those treated with Vd The patient's median TTNT (Table 2)
.
Table 2: Efficacy of patients in different cytogenetic subgroups between the two treatment groups.
The OS of patients in the high-risk and standard-risk subgroups tends to support patients receiving XVd treatment
.
In addition, although the statistical difference was not reached, the patients receiving XVd in the standard risk group and the high-risk group had a lower mortality trend than Vd treatment, which were 28.
7% and 43.
7%, respectively
.
3 Safety The safety analysis included 70 high-risk cytogenetic patients receiving XVd treatment and 70 high-risk cytogenetic patients receiving Vd treatment, 125 patients receiving XVd treatment and 134 standard risk cytogenetic patients receiving Vd treatment
.
The safety characteristics of XVd and Vd treatments were similar in the high-risk and standard-risk subgroups (Table 3)
.
Table 3: Adverse reactions of patients in different cytogenetic subgroups between the two treatment groups.
Conclusions The results of this study show that the oral XPO1 inhibitor Celinisol and its new mechanism of action can be used to treat high-risk or standard previous treatments Risk cytogenetic MM patients
.
Regardless of the MM cytogenetic risk, patients benefit from XVd treatment in terms of clinical outcomes better than Vd
.
References: Shambavi Richard, Ajai Chari, Sosana Delimpasi, et al.
Selinexor, bortezomib, and dexamethasone versus bortezomib and dexamethasone in previously treated multiple myeloma: Outcomes by cytogenetic risk.
Am J Hematol.
2021 Sep 1;96(9):1120 -1130.
Poke "read the original text" and we will make progress together
Patients who are suitable for transplantation are subsequently treated with autologous hematopoietic stem cell transplantation (ASCT).
) Maintenance treatment is given after consolidation treatment
.
Although there are a variety of highly effective new drugs for MM, almost all patients will relapse and require follow-up treatment
.
MM cytogenetic abnormalities can affect clinical outcomes, accompanied by high-risk abnormalities in cytogenetics, such as del(17p), t(4;14), t(14;16) and 1q21 amplification, and accompanied by standard risk cytogenetics Compared with patients, they have shorter progression-free survival (PFS) and overall survival (OS)
.
Therefore, new treatment options are needed to overcome the poor prognosis of these patients with relapsed or refractory MM (R/R MM) accompanied by high-risk cytogenetic changes
.
Celinisol is a potent, oral, selective nuclear export inhibitor (SINE) compound
.
The BOSTON trial is a phase III clinical study.
The previous results showed that Celinisol combined with bortezomib and dexamethasone (XVd) significantly improved the overall survival rate (ORR) and The median PFS is associated with a lower incidence of peripheral neuropathy, and OS also tends to benefit
.
Based on this, some researchers analyzed whether combining Celinisol on the basis of Vd can improve the prognosis of patients with high-risk R/R MM
.
Research methods The BOSTON trial is an international, open-label, randomized, phase III clinical study
.
According to the International Myeloma Working Group (IMWG) criteria, patients aged ≥18 years, histologically confirmed MM, and previously received 1-3 systemic anti-MM regimens were included
.
The patients included in the study were randomly assigned (1:1) to the XVd or Vd group according to the previous PI treatment (yes or not), the number of previous anti-MM treatment regimens (1 vs 2-3) and the revised international staging system ( R-ISS; I-II vs III) to determine the disease stage for randomization and stratification
.
The primary endpoint was PFS assessed by the independent review committee, and the secondary endpoints included OS, ORR, duration of remission (DOR), time to next treatment (TTNT), incidence of peripheral neuropathy ≥2 and safety
.
Research results 1 Patient characteristics The BOSTON study included a total of 402 MM patients who had previously received 1-3 lines of treatment and received randomization, including 195 cases in the XVd group and 207 cases in the Vd group
.
Among them, 141 patients (35.
1%) had high-risk cytogenetic abnormalities, 70 patients in the XVd group and 71 patients in the Vd group; 261 (64.
9%) patients were standard risk cytogenetic MM, and the XVd group patients were 125, 136 patients in the Vd group
.
In the subgroups defined by cytogenetic risk, the baseline demographics and disease characteristics of patients were evenly distributed between the two treatment groups (see Table 1 for details)
.
Among patients in the two treatment groups, 1q21 amplification was the most common cytogenetic abnormality, with 22.
1% in the XVd group and 18.
8% in the Vd group
.
The proportion of men with high-risk cytogenetic characteristics is even lower
.
The bortezomib-containing regimen is the most commonly used previous treatment, followed by the lenalidomide-containing regimen
.
Table 1: Baseline characteristics of patients 2 Among patients with high-risk cytogenetic abnormalities in efficacy, patients treated with XVd had longer median PFS than Vd, which were 12.
91 months and 8.
61 months (HR 0.
73; 95%) CI, 0.
47-1.
14; one-sided p=0.
0827) (Figure 1)
.
Also in standard-risk cytogenetic patients, patients treated with XVd compared with Vd also had longer median PFS distributions of 16.
62 months and 9.
46 months (HR 0.
61; 95% CI, 0.
42–0.
88; unilateral p=0.
0036) (Figure 1)
.
Figure 1: Patients with different cytogenetic subgroups between the two treatment groups have high risk of PFS (78.
6% vs 57.
7%; unilateral p=0.
0041) and standard risk (75.
2% vs 64.
7%; p=0.
0329) subgroups, Patients treated with XVd had higher ORR than Vd (Table 2)
.
In addition, in the high-risk subgroup, the proportion of patients in the XVd group who achieved ≥Very good partial remission (VGPR) was also significantly higher than that in the Vd group (30.
0% vs 18.
3%)
.
Patients in the standard-risk and high-risk groups who received XVd had a lower disease progression (PD) rate than those treated with Vd
.
In addition, in the high-risk (14.
03 vs 8.
61 months; one-sided p = 0.
0178) and standard risk (18.
23 vs 11.
73 months; one-sided p = 0.
0178) subgroups, patients who received XVd were significantly longer than those treated with Vd The patient's median TTNT (Table 2)
.
Table 2: Efficacy of patients in different cytogenetic subgroups between the two treatment groups.
The OS of patients in the high-risk and standard-risk subgroups tends to support patients receiving XVd treatment
.
In addition, although the statistical difference was not reached, the patients receiving XVd in the standard risk group and the high-risk group had a lower mortality trend than Vd treatment, which were 28.
7% and 43.
7%, respectively
.
3 Safety The safety analysis included 70 high-risk cytogenetic patients receiving XVd treatment and 70 high-risk cytogenetic patients receiving Vd treatment, 125 patients receiving XVd treatment and 134 standard risk cytogenetic patients receiving Vd treatment
.
The safety characteristics of XVd and Vd treatments were similar in the high-risk and standard-risk subgroups (Table 3)
.
Table 3: Adverse reactions of patients in different cytogenetic subgroups between the two treatment groups.
Conclusions The results of this study show that the oral XPO1 inhibitor Celinisol and its new mechanism of action can be used to treat high-risk or standard previous treatments Risk cytogenetic MM patients
.
Regardless of the MM cytogenetic risk, patients benefit from XVd treatment in terms of clinical outcomes better than Vd
.
References: Shambavi Richard, Ajai Chari, Sosana Delimpasi, et al.
Selinexor, bortezomib, and dexamethasone versus bortezomib and dexamethasone in previously treated multiple myeloma: Outcomes by cytogenetic risk.
Am J Hematol.
2021 Sep 1;96(9):1120 -1130.
Poke "read the original text" and we will make progress together
