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Barta SK , Jain R , Mazumder A , Carter J , Almanzar L , Browne R , Shahnaz S , Elkind R , Kaminetzky D , Battini R , Derman O , Kornblum N , Verma A , Braunschweig I
Pharmacokinetics-directed Intravenous Busulfan Combined With High-dose Melphalan and Bortezomib as a Conditioning Regimen for Patients With Multiple Myeloma
Clin Lymphoma Myeloma Leuk. 2017 Oct;17(10) :650-657
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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 muM x min. Patients received Btz (1 mg/m2 x 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 muM x 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.
2152-2669 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 Braunschweig, Ira Journal Article United States Clinical Trial, Phase II Research Support, Non-U.S. Gov't Clin Lymphoma Myeloma Leuk. 2017 Jun 17. pii: S2152-2650(17)30198-2. doi: 10.1016/j.clml.2017.06.005.