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Introduction Pabo Li daclizumab (Pembrolizumab) is an anti - programmed cell death pharmaceutical protein 1 (PD-1) is commonly utilized to treat metastatic melanoma, non-small cell lung cancer, esophageal cancer and other
.
There are currently studies applying pembrolizumab to the combined treatment of classic Hodgkin's lymphoma (cHL)
.
Today, the editor compiled two studies on pembrolizumab combined with other drugs in the treatment of cHL in the 2021 ASH annual meeting for the reference of readers
.
Abstract number: 229 Pembrolizumab combined with ICE chemotherapy produced a high complete metabolic remission rate for relapsed/refractory classic Hodgkin’s lymphoma (cHL): a multi-institution phase II trial with a research background of approximately 30 -35% of cHL patients will prove to be refractory to first-line treatment or later relapse
.
Traditional second-line chemotherapy regimens include ifosfamide, carboplatin, and etoposide (ICE), with a complete remission (CR) rate of about 50%
.
Before autologous hematopoietic stem cell transplantation (ASCT), complete metabolic remission (CMR) is assessed by PET/CT imaging, which can predict good progression-free survival (PFS) and overall survival (OS)
.
PD-1 blockade is a mature treatment strategy for the treatment of cHL, and pembrolizumab is an inhibitor that targets PD-1
.
The researchers hypothesized that before ASCT, pembrolizumab combined with ICE (PEM-ICE) chemotherapy can be used as a safe and effective regimen to obtain high CMR rates
.
Research Methods This single-arm, phase II, multi-institutional clinical trial evaluated the efficacy of PEM-ICE combined with chemotherapy in patients with relapsed and refractory cHL who meet the criteria of ASCT
.
The program uses a 21-day cycle.
Pembrolizumab 200 mg is used intravenously on the first day, and a standard dose of ICE is used on the second day (ifosfamide 5g/m2 and mesna are continuously infused for 24 hours on the second day).
Carboplatin was injected intravenously with AUC 5 [maximum dose 800 mg] on 2 days, and etoposide 100 mg/m2/day was injected intravenously on day 1 to 3)
.
After two cycles of PEM-ICE, hematopoietic stem cell activation/collection is performed
.
Another cycle of pembrolizumab single-drug intravenous injection of 200 mg
.
The primary endpoint of the study was CMR in FDG-PET2 imaging, defined as Deauville score ≤ 3 points
.
Secondary endpoints include PFS and OS, safety and tolerability, and transplant-related indicators (including the ability to collect stem cells and the time to transplant)
.
The results of the study were 43 patients were enrolled, and 37 patients reached the primary endpoint
.
Fourteen patients (39%) had primary refractory cHL, 12 patients (32%) had cHL recurrence within one year, and 6 patients (16%) had masses greater than 10 cm when they were enrolled in the study
.
After two cycles of PEM-ICE treatment, the CMR rate assessed by PET/CT imaging was 86.
5% (95% CI, 71.
2-95%), reaching the primary endpoint, which was a 70% improvement over the historical results
.
The ORR of PET2 was 97.
3%, the PR rate was 11%, and the PD rate was 2.
7%
.
In the PET2 score, 45% were Deauville 1 (n=17), 27% were Deauville 2 (n=10), 8.
1% were Deauville 3 (n=3), and 13.
5% were Deauville 4 (n=5).
), and 5.
4% is Deauville 5 points (n=2)
.
Thirty-five of 37 evaluable patients underwent ASCT
.
Seven patients received radiotherapy as part of the preconditioning regimen, and another 4 patients received consolidation radiotherapy after transplantation
.
After a median follow-up of 27 months, the 2-year PFS rate was 88.
2%, and the OS rate was 95.
1%
.
A total of 40 patients underwent hematopoietic stem cell activation/collection and ASCT.
The absolute neutrophil count of the patients rose on the 11th day (range 9-24 days), and the platelet count rebounded on the 12th day (range 8-23 days)
.
Among the 42 patients with evaluable toxicity, the common grade 3-4 hematological adverse events (AE) included 39 cases of thrombocytopenia (93%), 32 cases of anemia (76%), and 12 cases of febrile neutropenia ( 29%)
.
Non-hematological toxicities of grade 3-4 were mostly hypokalemia in 15 cases (36%), hypophosphatemia in 11 cases (26%), and oral mucositis in 10 cases (24%)
.
One patient had an autoimmune event related to pembrolizumab, and the patient had a transplant syndrome, that is, acute respiratory distress syndrome after ASCT.
This symptom and cardiac arrest during the collection of hematopoietic stem cells belong to grade 5 toxicity
.
Research conclusions Pembrolizumab+ICE chemotherapy regimen is a tolerable and effective regimen.
The CMR rate assessed by PET/CT is very high, and it can be used as a salvage therapy for patients with ASCT
.
The results of short-term follow-up showed that the patient had good PFS and OS after transplantation
.
Abstract number: 233 Pembrolizumab and AVD are used at the same time for untreated classical Hodgkin’s lymphoma.
Research background ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) program is North America The standard first-line therapy for cHL
.
In this program, the use of verbutuximab instead of bleomycin proved to improve the efficacy of advanced patients, but also increased toxicity (Connors et al NEJM 2017)
.
PD-1 inhibitors have high activity in relapsed/refractory cHL
.
A researcher conducted a study to explore the safety and efficacy of pembrolizumab and AVD combination (APVD) in the first-line treatment of cHL patients
.
Research Method This is a single-arm, single-center pilot study that uses APVD for treatment of untreated cHL at any stage
.
The study was based on the intravenous administration of 200 mg pembrolizumab every 21 days, and the standard dose of AVD every 14 days
.
After 2 cycles of medication, the patient was tested for FDG-PET2
.
According to the patient's baseline level and disease risk factors, it is determined whether the patient needs another 4 weeks of APVD treatment
.
After the treatment, all patients underwent PET/CT examination again
.
The primary endpoint of the study was that >85% of cHL patients completed 2 cycles of APVD treatment without delay, which was used to test the safety of the APVD regimen
.
The secondary endpoints were the CR rate and FDG-PET2 negative rate after 2 cycles of APVD treatment
.
The exploratory endpoints were related factors affecting PFS, OS and ctDNA in patients with cHL
.
Research Results A total of 30 patients were included in the study, all of whom had received at least 2 cycles of APVD treatment, and 22 patients (73%) received 6 cycles of treatment
.
The median age of the patients was 32 years (range 18-69 years)
.
Most patients are advanced (n=1[3%] in stage I, n=11[37%] in stage II, n=7[23%] in stage III, n=11 in stage IV, [37%])
.
Thirteen patients (43%) had type B symptoms at the time of diagnosis, and 5 patients (17%) had mass lesions
.
There were no deaths in the safety study
.
Common grade 3-4 non-hematological AEs were febrile neutropenia (5 cases, 17%), hyponatremia (3 cases, 10%), and syncope (3 cases, 10%)
.
One patient had Grade 4 colorectal obstruction/abscess
.
Six patients missed ≥1 dose of pembrolizumab, and 5 of them were due to a grade ≥2 reversible increase in transaminases
.
Immune-related AEs include elevated alanine aminotransferase (ALT) (20 cases, 67%), elevated serum aspartate aminotransferase (AST) (10 cases, 33%), and skin rash (13 cases, 43%)
.
Only one patient had grade 4 transaminase elevation
.
All untoward symptoms can be relieved through research prescribed programs, including the use of necessary cortisol drugs
.
Efficacy Among the 30 selected patients, 29 patients can be evaluated for efficacy, and one patient refused to receive mid-term PET and further treatment
.
The results of FDG-PET2 showed that 10 patients achieved PR, 19 patients achieved CR, the CR rate was 66%, and the ORR rate was 100%
.
No patients experienced treatment delays> 21 days in the first 2 cycles
.
At the end of the treatment, PET showed that all patients had a CR rate of 81%, and only one patient showed a conversion from CR to PR after two PET results, which was considered disease progression
.
The median follow-up time was 16.
2 months, the 1-year PFS rate was 96%, and the OS rate was 100%
.
So far, no patients have discontinued or discontinued treatment due to AE progression
.
The study concluded that the combination of pembrolizumab and AVD is a safe and effective front-line treatment for HL
.
In the APVD regimen, elevated transaminase is more common than in the ABVD regimen, but it can be reversed
.
Positive FDG-PET2 after APVD does not seem to be associated with a high risk of disease recurrence
.
The APVD regimen represents a well-tolerated and effective therapy, which can be further evaluated at all stages of cHL
.
References [1] Locke J.
Bryan, et al.
2021 ASH.
Abstract #229.
[2] Ryan C.
Lynch, et al.
2021 ASH.
Abstract #233.
Stamp "read the original text", we will make progress together
.
There are currently studies applying pembrolizumab to the combined treatment of classic Hodgkin's lymphoma (cHL)
.
Today, the editor compiled two studies on pembrolizumab combined with other drugs in the treatment of cHL in the 2021 ASH annual meeting for the reference of readers
.
Abstract number: 229 Pembrolizumab combined with ICE chemotherapy produced a high complete metabolic remission rate for relapsed/refractory classic Hodgkin’s lymphoma (cHL): a multi-institution phase II trial with a research background of approximately 30 -35% of cHL patients will prove to be refractory to first-line treatment or later relapse
.
Traditional second-line chemotherapy regimens include ifosfamide, carboplatin, and etoposide (ICE), with a complete remission (CR) rate of about 50%
.
Before autologous hematopoietic stem cell transplantation (ASCT), complete metabolic remission (CMR) is assessed by PET/CT imaging, which can predict good progression-free survival (PFS) and overall survival (OS)
.
PD-1 blockade is a mature treatment strategy for the treatment of cHL, and pembrolizumab is an inhibitor that targets PD-1
.
The researchers hypothesized that before ASCT, pembrolizumab combined with ICE (PEM-ICE) chemotherapy can be used as a safe and effective regimen to obtain high CMR rates
.
Research Methods This single-arm, phase II, multi-institutional clinical trial evaluated the efficacy of PEM-ICE combined with chemotherapy in patients with relapsed and refractory cHL who meet the criteria of ASCT
.
The program uses a 21-day cycle.
Pembrolizumab 200 mg is used intravenously on the first day, and a standard dose of ICE is used on the second day (ifosfamide 5g/m2 and mesna are continuously infused for 24 hours on the second day).
Carboplatin was injected intravenously with AUC 5 [maximum dose 800 mg] on 2 days, and etoposide 100 mg/m2/day was injected intravenously on day 1 to 3)
.
After two cycles of PEM-ICE, hematopoietic stem cell activation/collection is performed
.
Another cycle of pembrolizumab single-drug intravenous injection of 200 mg
.
The primary endpoint of the study was CMR in FDG-PET2 imaging, defined as Deauville score ≤ 3 points
.
Secondary endpoints include PFS and OS, safety and tolerability, and transplant-related indicators (including the ability to collect stem cells and the time to transplant)
.
The results of the study were 43 patients were enrolled, and 37 patients reached the primary endpoint
.
Fourteen patients (39%) had primary refractory cHL, 12 patients (32%) had cHL recurrence within one year, and 6 patients (16%) had masses greater than 10 cm when they were enrolled in the study
.
After two cycles of PEM-ICE treatment, the CMR rate assessed by PET/CT imaging was 86.
5% (95% CI, 71.
2-95%), reaching the primary endpoint, which was a 70% improvement over the historical results
.
The ORR of PET2 was 97.
3%, the PR rate was 11%, and the PD rate was 2.
7%
.
In the PET2 score, 45% were Deauville 1 (n=17), 27% were Deauville 2 (n=10), 8.
1% were Deauville 3 (n=3), and 13.
5% were Deauville 4 (n=5).
), and 5.
4% is Deauville 5 points (n=2)
.
Thirty-five of 37 evaluable patients underwent ASCT
.
Seven patients received radiotherapy as part of the preconditioning regimen, and another 4 patients received consolidation radiotherapy after transplantation
.
After a median follow-up of 27 months, the 2-year PFS rate was 88.
2%, and the OS rate was 95.
1%
.
A total of 40 patients underwent hematopoietic stem cell activation/collection and ASCT.
The absolute neutrophil count of the patients rose on the 11th day (range 9-24 days), and the platelet count rebounded on the 12th day (range 8-23 days)
.
Among the 42 patients with evaluable toxicity, the common grade 3-4 hematological adverse events (AE) included 39 cases of thrombocytopenia (93%), 32 cases of anemia (76%), and 12 cases of febrile neutropenia ( 29%)
.
Non-hematological toxicities of grade 3-4 were mostly hypokalemia in 15 cases (36%), hypophosphatemia in 11 cases (26%), and oral mucositis in 10 cases (24%)
.
One patient had an autoimmune event related to pembrolizumab, and the patient had a transplant syndrome, that is, acute respiratory distress syndrome after ASCT.
This symptom and cardiac arrest during the collection of hematopoietic stem cells belong to grade 5 toxicity
.
Research conclusions Pembrolizumab+ICE chemotherapy regimen is a tolerable and effective regimen.
The CMR rate assessed by PET/CT is very high, and it can be used as a salvage therapy for patients with ASCT
.
The results of short-term follow-up showed that the patient had good PFS and OS after transplantation
.
Abstract number: 233 Pembrolizumab and AVD are used at the same time for untreated classical Hodgkin’s lymphoma.
Research background ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) program is North America The standard first-line therapy for cHL
.
In this program, the use of verbutuximab instead of bleomycin proved to improve the efficacy of advanced patients, but also increased toxicity (Connors et al NEJM 2017)
.
PD-1 inhibitors have high activity in relapsed/refractory cHL
.
A researcher conducted a study to explore the safety and efficacy of pembrolizumab and AVD combination (APVD) in the first-line treatment of cHL patients
.
Research Method This is a single-arm, single-center pilot study that uses APVD for treatment of untreated cHL at any stage
.
The study was based on the intravenous administration of 200 mg pembrolizumab every 21 days, and the standard dose of AVD every 14 days
.
After 2 cycles of medication, the patient was tested for FDG-PET2
.
According to the patient's baseline level and disease risk factors, it is determined whether the patient needs another 4 weeks of APVD treatment
.
After the treatment, all patients underwent PET/CT examination again
.
The primary endpoint of the study was that >85% of cHL patients completed 2 cycles of APVD treatment without delay, which was used to test the safety of the APVD regimen
.
The secondary endpoints were the CR rate and FDG-PET2 negative rate after 2 cycles of APVD treatment
.
The exploratory endpoints were related factors affecting PFS, OS and ctDNA in patients with cHL
.
Research Results A total of 30 patients were included in the study, all of whom had received at least 2 cycles of APVD treatment, and 22 patients (73%) received 6 cycles of treatment
.
The median age of the patients was 32 years (range 18-69 years)
.
Most patients are advanced (n=1[3%] in stage I, n=11[37%] in stage II, n=7[23%] in stage III, n=11 in stage IV, [37%])
.
Thirteen patients (43%) had type B symptoms at the time of diagnosis, and 5 patients (17%) had mass lesions
.
There were no deaths in the safety study
.
Common grade 3-4 non-hematological AEs were febrile neutropenia (5 cases, 17%), hyponatremia (3 cases, 10%), and syncope (3 cases, 10%)
.
One patient had Grade 4 colorectal obstruction/abscess
.
Six patients missed ≥1 dose of pembrolizumab, and 5 of them were due to a grade ≥2 reversible increase in transaminases
.
Immune-related AEs include elevated alanine aminotransferase (ALT) (20 cases, 67%), elevated serum aspartate aminotransferase (AST) (10 cases, 33%), and skin rash (13 cases, 43%)
.
Only one patient had grade 4 transaminase elevation
.
All untoward symptoms can be relieved through research prescribed programs, including the use of necessary cortisol drugs
.
Efficacy Among the 30 selected patients, 29 patients can be evaluated for efficacy, and one patient refused to receive mid-term PET and further treatment
.
The results of FDG-PET2 showed that 10 patients achieved PR, 19 patients achieved CR, the CR rate was 66%, and the ORR rate was 100%
.
No patients experienced treatment delays> 21 days in the first 2 cycles
.
At the end of the treatment, PET showed that all patients had a CR rate of 81%, and only one patient showed a conversion from CR to PR after two PET results, which was considered disease progression
.
The median follow-up time was 16.
2 months, the 1-year PFS rate was 96%, and the OS rate was 100%
.
So far, no patients have discontinued or discontinued treatment due to AE progression
.
The study concluded that the combination of pembrolizumab and AVD is a safe and effective front-line treatment for HL
.
In the APVD regimen, elevated transaminase is more common than in the ABVD regimen, but it can be reversed
.
Positive FDG-PET2 after APVD does not seem to be associated with a high risk of disease recurrence
.
The APVD regimen represents a well-tolerated and effective therapy, which can be further evaluated at all stages of cHL
.
References [1] Locke J.
Bryan, et al.
2021 ASH.
Abstract #229.
[2] Ryan C.
Lynch, et al.
2021 ASH.
Abstract #233.
Stamp "read the original text", we will make progress together
