Phase III trial of bortezomib, cyclophosphamide and dexamethasone in newly diagnosed myeloma

We aimed at demonstrating non-inferiority of bortezomib/cyclophosphamide/dexamethasone (VCD) compared to bortezomib/ doxorubicin/dexamethasone (PAd) induction therapy with respect to very good partial response rates or better (≥ VGPR) in 504 newly diagnosed, transplant-eligible multiple myeloma patients. VCD was found to be non-inferior to PAd with respect to > VGPR rates (37.0 versus 34.3%, P = 0.001). The rates of progressive disease (PD) were 0.4% (VCD) versus 4.8% (PAd; P = 0.003). In the PAd arm, 11 of 12 patients with PD had either renal impairment (creatinine ≥ 2 mg/dl) at diagnosis or the cytogenetic abnormality gain 1q21, whereas no PD was observed in these subgroups in the VCD arm. Leukocytopenia/neutropenia ([greater than or equal to] 3°) occurred more frequently in the VCD arm (35.2% versus 11.3%, P < 0.001). Neuropathy rates (≥ 2°) were higher in the PAd group (14.9 versus 8.4%, P = 0.03). Serious adverse events, both overall and those related to thromboembolic events, were higher in the PAd group (32.7 versus 24.0%, P = 0.04 and 2.8 versus 0.4%, P = 0.04). Stem cell collection was not impeded by VCD. VCD is as effective as PAd in terms of achieving ≥ VGPR rates with fewer PD and has a favorable toxicity profile. Therefore, VCD is preferable to PAd as induction therapy. Leukemia (2015) 29, 1721-1729; doi:10.1038/leu.2015.80