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Addition Of Bortezemib To High Dose Melphalan Does Not Improve Response Rate Or Progression-Free Survival

Year: 2010

Type: article

Abstract: High dose melphalan remains the preparative regimen of choice for autologous hematopoietic stem cell transplantation (auto HCT) in multiple myeloma (MM). Bortezomib is an active agent in newly diagnosed or relapsed MM, and has synergistic activity with melphalan. We recently conducted two randomized phase II trials in MM, one of which studied the safety and efficacy of adding bortezomib to high-dose melphalan in the preparative regimen for auto HCT. Here we report the response rates, progression-free survival (PFS) and overall survival (OS) between the melphalan-based preparative regimens with or without bortezomib. In the first randomized trial 48 patients received high-dose Melphalan at 100 mg/m2 IV on days -4 and -3, and ascorbic acid (AA) 1000 mg IV daily on days -9 to -3. Patients in arm 1 did not receive arsenic trioxide (ATO); patients in arm 2 received ATO 0.15 mg/kg IV from days -9 to -3; patients in arm 3 received ATO at 0.25 mg/kg from days -9 to -3. In the second randomized trial 60 patients were enrolled and 58 received an auto HCT with a preparative regimen of melphalan 100 mg/m2 IV on days -4 and -3, AA 1000 mg/day IV on days -9 to -3 and ATO 0.25 mg/kg IV on days -9 to -3. Patients in the second trial were randomized to 3 arms; no bortezomib (arm 1), bortezomib 1 mg/m2 on days -9, -6 and -3 (arm 2), and bortezomib 1.5 mg/m2 on days -9, -6 and -3 (arm 3). A total of 106 patients received an auto HCT in these 2 trials. Of 106 patients, 39 received a preparative regimen with bortezomib (Group A) and 67 without bortezomib (Group B). Patient characteristics and outcome are summarized in Table 1. Patients in group B (without bortezomib) were slightly older, had a longer interval between diagnosis and auto HCT and 21% had a prior auto HCT (vs. 2% in group A). Complete + very good partial response rates (CR+VGPR) in groups A and B were similar (31% vs. 31%). Median PFS and OS in group A vs. B were 14 vs. 23 months (p=0.08) and 80 vs. 82 months (p=0.17), respectively. In this analysis of 106 patients, adding bortezomib to a HD melphalan preparative regimen did not improve the response rate, PFS or OS.Tabled 1Patient Characteristics and OutcomesGroup A (Bortezomib)Group B (No Bortezomib)Number of patients3967Median age5955Abnormal cytogenetics1311Relapsed disease1025Prior auto HCT114Months from diagnosis to auto HCT914Median CD34 dose 106/kg3.94.56Median days to engraftment1010Grade 3-4 adverse effects1220CR7 (18%)16 (24%)CR+VGPR12 (31%)22 (31%)Median PFS (months)1423Median OS (months)8082 Open table in a new tab

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2009.12.147