Abstract
Background: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has a well-established role in the treatment of patients with multiple myeloma. Melphalan 200 mg/m2 (Mel200) is the most commonly used preparative regimen. Several studies have provided evidence for potential synergism and safety when combining bortezomib (Btz) or busulfan (Bu) with melphalan (Mel). Patients and Methods: We conducted a prospective phase II study to investigate the safety and efficacy of conditioning with pharmacokinetics (PK)-directed intravenous (IV) Bu with Btz and Mel. Bu dosing was adjusted to target a total area under the curve (AUC) of 20,000 μM × min. Patients received Btz (1 mg/m2 × 4 doses) and Mel (140 mg/m2). Results: A total of 19 subjects were enrolled. Their median age was 55 years, and the median follow-up period was 23.7 months. PK testing resulted in 86% of patients achieving an estimated total AUC of 20,000 ± 2500 μM × min. The overall response rate (ORR) at day +100 after ASCT was 100% in the evaluable patients, with 11% of patients achieving a complete response. The 2-year progression-free survival rate was 57.9% (95% confidence interval [CI], 38%-89%), and the 2-year overall survival rate was 88.5% (95% CI, 76%-100%). The most common grade 3 and 4 toxicities were febrile neutropenia, dysphagia/odynophagia, and oral mucositis. No case of hepatic sinusoidal obstruction syndrome developed. One treatment-related mortality occurred before day +100. Conclusion: A preparative regimen of PK-directed IV Bu with Btz and Mel led to an ORR of 100% with acceptable toxicity and should be considered for direct comparison with the Mel200 regimen in future trials.
| Original language | English (US) |
|---|---|
| Journal | Clinical Lymphoma, Myeloma and Leukemia |
| DOIs | |
| State | Accepted/In press - 2017 |
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Keywords
- Autologous stem cell transplant
- High-dose chemotherapy
- Personalized medicine
- Proteasome inhibition
- Targeted therapy
ASJC Scopus subject areas
- Hematology
- Oncology
- Cancer Research
Cite this
Pharmacokinetics-directed Intravenous Busulfan Combined With High-dose Melphalan and Bortezomib as a Conditioning Regimen for Patients With Multiple Myeloma. / Barta, Stefan K.; Jain, Rishi; Mazumder, Amithaba; Carter, Jason; Almanzar, Lawrence; Browne, Roy; Shahnaz, Samira; Elkind, Richard; Kaminetzky, David; Battini, Ramakrishna; Derman, Olga; Kornblum, Noah; Verma, Amit K.; Braunschweig, Ira.
In: Clinical Lymphoma, Myeloma and Leukemia, 2017.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pharmacokinetics-directed Intravenous Busulfan Combined With High-dose Melphalan and Bortezomib as a Conditioning Regimen for Patients With Multiple Myeloma
AU - Barta, Stefan K.
AU - Jain, Rishi
AU - Mazumder, Amithaba
AU - Carter, Jason
AU - Almanzar, Lawrence
AU - Browne, Roy
AU - Shahnaz, Samira
AU - Elkind, Richard
AU - Kaminetzky, David
AU - Battini, Ramakrishna
AU - Derman, Olga
AU - Kornblum, Noah
AU - Verma, Amit K.
AU - Braunschweig, Ira
PY - 2017
Y1 - 2017
N2 - Background: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has a well-established role in the treatment of patients with multiple myeloma. Melphalan 200 mg/m2 (Mel200) is the most commonly used preparative regimen. Several studies have provided evidence for potential synergism and safety when combining bortezomib (Btz) or busulfan (Bu) with melphalan (Mel). Patients and Methods: We conducted a prospective phase II study to investigate the safety and efficacy of conditioning with pharmacokinetics (PK)-directed intravenous (IV) Bu with Btz and Mel. Bu dosing was adjusted to target a total area under the curve (AUC) of 20,000 μM × min. Patients received Btz (1 mg/m2 × 4 doses) and Mel (140 mg/m2). Results: A total of 19 subjects were enrolled. Their median age was 55 years, and the median follow-up period was 23.7 months. PK testing resulted in 86% of patients achieving an estimated total AUC of 20,000 ± 2500 μM × min. The overall response rate (ORR) at day +100 after ASCT was 100% in the evaluable patients, with 11% of patients achieving a complete response. The 2-year progression-free survival rate was 57.9% (95% confidence interval [CI], 38%-89%), and the 2-year overall survival rate was 88.5% (95% CI, 76%-100%). The most common grade 3 and 4 toxicities were febrile neutropenia, dysphagia/odynophagia, and oral mucositis. No case of hepatic sinusoidal obstruction syndrome developed. One treatment-related mortality occurred before day +100. Conclusion: A preparative regimen of PK-directed IV Bu with Btz and Mel led to an ORR of 100% with acceptable toxicity and should be considered for direct comparison with the Mel200 regimen in future trials.
AB - Background: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has a well-established role in the treatment of patients with multiple myeloma. Melphalan 200 mg/m2 (Mel200) is the most commonly used preparative regimen. Several studies have provided evidence for potential synergism and safety when combining bortezomib (Btz) or busulfan (Bu) with melphalan (Mel). Patients and Methods: We conducted a prospective phase II study to investigate the safety and efficacy of conditioning with pharmacokinetics (PK)-directed intravenous (IV) Bu with Btz and Mel. Bu dosing was adjusted to target a total area under the curve (AUC) of 20,000 μM × min. Patients received Btz (1 mg/m2 × 4 doses) and Mel (140 mg/m2). Results: A total of 19 subjects were enrolled. Their median age was 55 years, and the median follow-up period was 23.7 months. PK testing resulted in 86% of patients achieving an estimated total AUC of 20,000 ± 2500 μM × min. The overall response rate (ORR) at day +100 after ASCT was 100% in the evaluable patients, with 11% of patients achieving a complete response. The 2-year progression-free survival rate was 57.9% (95% confidence interval [CI], 38%-89%), and the 2-year overall survival rate was 88.5% (95% CI, 76%-100%). The most common grade 3 and 4 toxicities were febrile neutropenia, dysphagia/odynophagia, and oral mucositis. No case of hepatic sinusoidal obstruction syndrome developed. One treatment-related mortality occurred before day +100. Conclusion: A preparative regimen of PK-directed IV Bu with Btz and Mel led to an ORR of 100% with acceptable toxicity and should be considered for direct comparison with the Mel200 regimen in future trials.
KW - Autologous stem cell transplant
KW - High-dose chemotherapy
KW - Personalized medicine
KW - Proteasome inhibition
KW - Targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=85023777215&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85023777215&partnerID=8YFLogxK
U2 - 10.1016/j.clml.2017.06.005
DO - 10.1016/j.clml.2017.06.005
M3 - Article
C2 - 28684379
AN - SCOPUS:85023777215
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
SN - 2152-2669
ER -