VCd versus VRd in Newly Diagnosed Multiple Myeloma: Matched Real-World Analysis from the Balkan Myeloma Study Group (BMSG)

Abstract

Background: Bortezomib, dexamethasone and cyclophosphamide (VCd) remains a popular regimen, due to its activity and low toxicity, while bortezomib, lenalidomide and dexamethasone (VRd) is widely used in US and Europe; both are combined with anti-CD38 monoclonal antibodies but VCd and VRd have not been compared directly in adequately powered prospective trials.

Aim: We compared the outcomes of 1216 patients treated with VCd (N = 690) or VRd (N = 526) in a real-world setting.

Results: Patients treated with VCd had more often severe renal dysfunction, ISS-3 disease, hypercalcemia, elevated LDH, anemia, thrombocytopenia, poor performance while VRd-treated were older and received less often autologous transplant but more frequently maintenance but the duration of induction was similar. VRd was associated with substantially higher overall response and CR/VGPR rates to induction(P < .001) and improved PFS and OS in univariate analysis, especially among patients with standard risk disease, without renal dysfunction and in the elderly; however, in multivariate analysis there was no significant difference in either PFS or OS. In patients strictly matched 1:1 for major prognostic variables (188 in each group, total N = 376), the superiority of VRd in terms of responses rates and depth of response was confirmed, but without significant PFS or OS difference.

Conclusion: VRd is a more active induction regimen than VCd, although use of maintenance with lenalidomide may dilute the PFS or OS benefit. VCd induction remains an option in special circumstances. With the implementation of monoclonal antibodies, VCd backbone can be considered for patients without access to or who do not tolerate VRd.

Keywords: Bortezomib; High-risk myeloma; Induction therapy; Lenalidomide; Prognosis; Resistance.