Randomised phase II study to optimise melphalan, prednisolone, and bortezomib in untreated multiple myeloma (JCOG1105)

We conducted a randomised phase II study to determine the optimal dose and schedule of melphalan, prednisone, and bortezomib (MPB) (jRCTs031180097). Transplant-ineligible untreated multiple myeloma patients were randomised to Arm A (twice weekly bortezomib in one six-week cycle followed by eight five-week cycles of four times once weekly bortezomib with melphalan and prednisolone on days 1-4) or Arm B (nine four-week cycles of three times once weekly bortezomib with melphalan and prednisolone on days 1-4). The primary end-point was complete response (CR) rate. Of 91 patients randomised to two arms, 88 were eligible. The median cumulative bortezomib doses were 45 center dot 8 and 35 center dot 1 mg/m(2), CR rate was 18 center dot 6% [95% confidence interval (CI) 8 center dot 4-33 center dot 4] and 6 center dot 7% (95% CI 1 center dot 4-18 center dot 3), and the median progression-free survival (PFS) was 2 center dot 5 and 1 center dot 4 years in Arms A and B [hazard ratio (HR) 1 center dot 93 (95% CI 1 center dot 09-3 center dot 42)], respectively. Frequent grade >= 3 haematologic toxicities in Arms A and B were neutropenia (64 center dot 4% vs. 28 center dot 3%) and thrombocytopenia (35 center dot 6% vs. 10 center dot 9%). Grade 2/3 peripheral neuropathy was observed in 24 center dot 4/2 center dot 2% in Arm A and 8 center dot 7/0% in Arm B. In conclusion, Arm A was the more promising regimen, suggesting that the twice weekly schedule of bortezomib in the first cycle and higher cumulative dose of both bortezomib and melphalan influences the efficacy of modified MPB.