A PHARMACOKINETICS CLINICAL STUDY OF BORTEZOMIB SUBCUTANEOUS INJECTION VERSUS INTRAVENOUS INJECTION COMBINED WITH CHEMOTHERAPY IN CHINESE PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA-INTERIM RESULTS
(Abstract release date: 05/19/16)
EHA Library. Fu Z. 06/09/16; 134878; PB1978
Prof. Dr. Zhengzheng Fu
Contributions
Contributions
Abstract
Abstract: PB1978
Type: Publication Only
Background
Bortezomib was licensed for administration as a bolus i.v. injection. This route of administration has demonstrated efficacy and safety in previously untreated patients with multiple myeloma (MM). However, the i.v. route can be a potential barrier to treatment for patients with poor venous access and limits prescribing flexibility. Subcutaneous（SC） administration of bortezomib showed the advantage in safety and comparable efficacy compared with IV administration.
Aims
However, there is no PK data of bortezomib SC administration for Chinese patients. Our trial was to investigate the pharmacokinetics of the two routes of administration in Chinese population. Demographic and baseline characteristic, pharmacokinetics and safety data till the first VD treatment completion were reported here. (ClinicalTrial.gov Identifier: NCT01812096 )
Methods
This was a randomized, single-center, open-label study. The study included the following 4 sections: screening, VD regimen therapy (blood samples collection for PK analysis), extended treatment period (PAD regimen and/or subsequent ASCT) and follow-up period. 20 patients were determined to be randomly assigned in a 1:1 ratio to receive bortezomib subcutaneous or intravenous administration combined with chemotherapy. SC or IV bortezomib was administered at 1.3mg/m2, d1, 4, 8, 11, combined with dexamethasone (10 mg, bid, i.v., d1~2, 4~5, 8~9, 11~12) in the 1st cycle, every 21days, following 2-4th cycles of PAD regimen, bortezomib was SC or IV administered at 1.3mg/m2 on d1, 4, 8, 11; Doxorubicin 40 mg/m2, i.v.d1; Dexamethasone (Dex) 10 mg, bid, i.v., d1~2, 4~5, 8~9, 11~12;.every 28 days. Patients who were eligible for transplant underwent ASCT after the 4th cycle. Patients who were not eligible for transplant continued the 5-6th cycle treatment of PAD regimen. The blood samples for pharmacokinetics analysis were collected at the 15 time points d1, 11-14 of the first VD treatment. Patients had maximum 6 months follow-up after completing or terminating the treatment.
Results
From September 2014 to June 2015, 21 patients (10 patients in SC group and 11 in IV group) were enrolled in our study. 18 patients (10 in SC group and 8 in IV group) enrolled in the pharmacokinetic analysis. Median age in SC group was 56.8 yrs and 57.5 yrs in IV group. 81.82% patients had IgG isotype in the IV group and 40.00% patients had IgA isotype in the SC group. A Higher proportion patient had light chain isotype (20.00%) in the SC group. The median accumulative dose of bortezomib in VD treatment was much the same in each group. Mean maximum plasma concentration (Cmax) was 46.56ng/ml in SC group and 182.45ng/ml in IV group. Median time to Cmax (Tmax) was longer in SC group (0.25 h) than in IV group (0.03h). Mean bortezomib systemic exposure (AUClast) was similar between SC injection and IV administration (234.83vs266.75). Inter-patient variability in Cmax (percent coefficient of variations) was 24.76 in SC group and 30.79 in IV group. Treatment related TEAEs were reported in 7 of 10 patients (70%) in SC group and 9 of 11(81.82%) in IV group. Treatment related Grade≥3 TEAEs were reported in 2 of 10 patients ( 20% ) in SC group and 3 of 11 patients (27.27%) in IV group. TEAE leading to drug discontinuation was only reported in 1 of 11 patients (9.09%) in IV group. No Serious TEAE was reported in either group. The incidence of neutropenia was higher in IV group.
Conclusion
In conclusion, our interim data suggest that SC administration is a promising alternative to IV administration. The efficacy and safety information will be further presented in the final results.Acknowledgments: This study was funded by Xi’an Janssen Pharmaceutical Co, Ltd.
Session topic: E-poster
Keyword(s): Bortezomib, Multiple myeloma, Pharmacokinetic, Subcutaneous
Type: Publication Only
Background
Bortezomib was licensed for administration as a bolus i.v. injection. This route of administration has demonstrated efficacy and safety in previously untreated patients with multiple myeloma (MM). However, the i.v. route can be a potential barrier to treatment for patients with poor venous access and limits prescribing flexibility. Subcutaneous（SC） administration of bortezomib showed the advantage in safety and comparable efficacy compared with IV administration.
Aims
However, there is no PK data of bortezomib SC administration for Chinese patients. Our trial was to investigate the pharmacokinetics of the two routes of administration in Chinese population. Demographic and baseline characteristic, pharmacokinetics and safety data till the first VD treatment completion were reported here. (ClinicalTrial.gov Identifier: NCT01812096 )
Methods
This was a randomized, single-center, open-label study. The study included the following 4 sections: screening, VD regimen therapy (blood samples collection for PK analysis), extended treatment period (PAD regimen and/or subsequent ASCT) and follow-up period. 20 patients were determined to be randomly assigned in a 1:1 ratio to receive bortezomib subcutaneous or intravenous administration combined with chemotherapy. SC or IV bortezomib was administered at 1.3mg/m2, d1, 4, 8, 11, combined with dexamethasone (10 mg, bid, i.v., d1~2, 4~5, 8~9, 11~12) in the 1st cycle, every 21days, following 2-4th cycles of PAD regimen, bortezomib was SC or IV administered at 1.3mg/m2 on d1, 4, 8, 11; Doxorubicin 40 mg/m2, i.v.d1; Dexamethasone (Dex) 10 mg, bid, i.v., d1~2, 4~5, 8~9, 11~12;.every 28 days. Patients who were eligible for transplant underwent ASCT after the 4th cycle. Patients who were not eligible for transplant continued the 5-6th cycle treatment of PAD regimen. The blood samples for pharmacokinetics analysis were collected at the 15 time points d1, 11-14 of the first VD treatment. Patients had maximum 6 months follow-up after completing or terminating the treatment.
Results
From September 2014 to June 2015, 21 patients (10 patients in SC group and 11 in IV group) were enrolled in our study. 18 patients (10 in SC group and 8 in IV group) enrolled in the pharmacokinetic analysis. Median age in SC group was 56.8 yrs and 57.5 yrs in IV group. 81.82% patients had IgG isotype in the IV group and 40.00% patients had IgA isotype in the SC group. A Higher proportion patient had light chain isotype (20.00%) in the SC group. The median accumulative dose of bortezomib in VD treatment was much the same in each group. Mean maximum plasma concentration (Cmax) was 46.56ng/ml in SC group and 182.45ng/ml in IV group. Median time to Cmax (Tmax) was longer in SC group (0.25 h) than in IV group (0.03h). Mean bortezomib systemic exposure (AUClast) was similar between SC injection and IV administration (234.83vs266.75). Inter-patient variability in Cmax (percent coefficient of variations) was 24.76 in SC group and 30.79 in IV group. Treatment related TEAEs were reported in 7 of 10 patients (70%) in SC group and 9 of 11(81.82%) in IV group. Treatment related Grade≥3 TEAEs were reported in 2 of 10 patients ( 20% ) in SC group and 3 of 11 patients (27.27%) in IV group. TEAE leading to drug discontinuation was only reported in 1 of 11 patients (9.09%) in IV group. No Serious TEAE was reported in either group. The incidence of neutropenia was higher in IV group.
Conclusion
In conclusion, our interim data suggest that SC administration is a promising alternative to IV administration. The efficacy and safety information will be further presented in the final results.Acknowledgments: This study was funded by Xi’an Janssen Pharmaceutical Co, Ltd.
Session topic: E-poster
Keyword(s): Bortezomib, Multiple myeloma, Pharmacokinetic, Subcutaneous
Abstract: PB1978
Type: Publication Only
Background
Bortezomib was licensed for administration as a bolus i.v. injection. This route of administration has demonstrated efficacy and safety in previously untreated patients with multiple myeloma (MM). However, the i.v. route can be a potential barrier to treatment for patients with poor venous access and limits prescribing flexibility. Subcutaneous（SC） administration of bortezomib showed the advantage in safety and comparable efficacy compared with IV administration.
Aims
However, there is no PK data of bortezomib SC administration for Chinese patients. Our trial was to investigate the pharmacokinetics of the two routes of administration in Chinese population. Demographic and baseline characteristic, pharmacokinetics and safety data till the first VD treatment completion were reported here. (ClinicalTrial.gov Identifier: NCT01812096 )
Methods
This was a randomized, single-center, open-label study. The study included the following 4 sections: screening, VD regimen therapy (blood samples collection for PK analysis), extended treatment period (PAD regimen and/or subsequent ASCT) and follow-up period. 20 patients were determined to be randomly assigned in a 1:1 ratio to receive bortezomib subcutaneous or intravenous administration combined with chemotherapy. SC or IV bortezomib was administered at 1.3mg/m2, d1, 4, 8, 11, combined with dexamethasone (10 mg, bid, i.v., d1~2, 4~5, 8~9, 11~12) in the 1st cycle, every 21days, following 2-4th cycles of PAD regimen, bortezomib was SC or IV administered at 1.3mg/m2 on d1, 4, 8, 11; Doxorubicin 40 mg/m2, i.v.d1; Dexamethasone (Dex) 10 mg, bid, i.v., d1~2, 4~5, 8~9, 11~12;.every 28 days. Patients who were eligible for transplant underwent ASCT after the 4th cycle. Patients who were not eligible for transplant continued the 5-6th cycle treatment of PAD regimen. The blood samples for pharmacokinetics analysis were collected at the 15 time points d1, 11-14 of the first VD treatment. Patients had maximum 6 months follow-up after completing or terminating the treatment.
Results
From September 2014 to June 2015, 21 patients (10 patients in SC group and 11 in IV group) were enrolled in our study. 18 patients (10 in SC group and 8 in IV group) enrolled in the pharmacokinetic analysis. Median age in SC group was 56.8 yrs and 57.5 yrs in IV group. 81.82% patients had IgG isotype in the IV group and 40.00% patients had IgA isotype in the SC group. A Higher proportion patient had light chain isotype (20.00%) in the SC group. The median accumulative dose of bortezomib in VD treatment was much the same in each group. Mean maximum plasma concentration (Cmax) was 46.56ng/ml in SC group and 182.45ng/ml in IV group. Median time to Cmax (Tmax) was longer in SC group (0.25 h) than in IV group (0.03h). Mean bortezomib systemic exposure (AUClast) was similar between SC injection and IV administration (234.83vs266.75). Inter-patient variability in Cmax (percent coefficient of variations) was 24.76 in SC group and 30.79 in IV group. Treatment related TEAEs were reported in 7 of 10 patients (70%) in SC group and 9 of 11(81.82%) in IV group. Treatment related Grade≥3 TEAEs were reported in 2 of 10 patients ( 20% ) in SC group and 3 of 11 patients (27.27%) in IV group. TEAE leading to drug discontinuation was only reported in 1 of 11 patients (9.09%) in IV group. No Serious TEAE was reported in either group. The incidence of neutropenia was higher in IV group.
Conclusion
In conclusion, our interim data suggest that SC administration is a promising alternative to IV administration. The efficacy and safety information will be further presented in the final results.Acknowledgments: This study was funded by Xi’an Janssen Pharmaceutical Co, Ltd.
Session topic: E-poster
Keyword(s): Bortezomib, Multiple myeloma, Pharmacokinetic, Subcutaneous
Type: Publication Only
Background
Bortezomib was licensed for administration as a bolus i.v. injection. This route of administration has demonstrated efficacy and safety in previously untreated patients with multiple myeloma (MM). However, the i.v. route can be a potential barrier to treatment for patients with poor venous access and limits prescribing flexibility. Subcutaneous（SC） administration of bortezomib showed the advantage in safety and comparable efficacy compared with IV administration.
Aims
However, there is no PK data of bortezomib SC administration for Chinese patients. Our trial was to investigate the pharmacokinetics of the two routes of administration in Chinese population. Demographic and baseline characteristic, pharmacokinetics and safety data till the first VD treatment completion were reported here. (ClinicalTrial.gov Identifier: NCT01812096 )
Methods
This was a randomized, single-center, open-label study. The study included the following 4 sections: screening, VD regimen therapy (blood samples collection for PK analysis), extended treatment period (PAD regimen and/or subsequent ASCT) and follow-up period. 20 patients were determined to be randomly assigned in a 1:1 ratio to receive bortezomib subcutaneous or intravenous administration combined with chemotherapy. SC or IV bortezomib was administered at 1.3mg/m2, d1, 4, 8, 11, combined with dexamethasone (10 mg, bid, i.v., d1~2, 4~5, 8~9, 11~12) in the 1st cycle, every 21days, following 2-4th cycles of PAD regimen, bortezomib was SC or IV administered at 1.3mg/m2 on d1, 4, 8, 11; Doxorubicin 40 mg/m2, i.v.d1; Dexamethasone (Dex) 10 mg, bid, i.v., d1~2, 4~5, 8~9, 11~12;.every 28 days. Patients who were eligible for transplant underwent ASCT after the 4th cycle. Patients who were not eligible for transplant continued the 5-6th cycle treatment of PAD regimen. The blood samples for pharmacokinetics analysis were collected at the 15 time points d1, 11-14 of the first VD treatment. Patients had maximum 6 months follow-up after completing or terminating the treatment.
Results
From September 2014 to June 2015, 21 patients (10 patients in SC group and 11 in IV group) were enrolled in our study. 18 patients (10 in SC group and 8 in IV group) enrolled in the pharmacokinetic analysis. Median age in SC group was 56.8 yrs and 57.5 yrs in IV group. 81.82% patients had IgG isotype in the IV group and 40.00% patients had IgA isotype in the SC group. A Higher proportion patient had light chain isotype (20.00%) in the SC group. The median accumulative dose of bortezomib in VD treatment was much the same in each group. Mean maximum plasma concentration (Cmax) was 46.56ng/ml in SC group and 182.45ng/ml in IV group. Median time to Cmax (Tmax) was longer in SC group (0.25 h) than in IV group (0.03h). Mean bortezomib systemic exposure (AUClast) was similar between SC injection and IV administration (234.83vs266.75). Inter-patient variability in Cmax (percent coefficient of variations) was 24.76 in SC group and 30.79 in IV group. Treatment related TEAEs were reported in 7 of 10 patients (70%) in SC group and 9 of 11(81.82%) in IV group. Treatment related Grade≥3 TEAEs were reported in 2 of 10 patients ( 20% ) in SC group and 3 of 11 patients (27.27%) in IV group. TEAE leading to drug discontinuation was only reported in 1 of 11 patients (9.09%) in IV group. No Serious TEAE was reported in either group. The incidence of neutropenia was higher in IV group.
Conclusion
In conclusion, our interim data suggest that SC administration is a promising alternative to IV administration. The efficacy and safety information will be further presented in the final results.Acknowledgments: This study was funded by Xi’an Janssen Pharmaceutical Co, Ltd.
Session topic: E-poster
Keyword(s): Bortezomib, Multiple myeloma, Pharmacokinetic, Subcutaneous
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