Randomized Phase II Study of Bortezomib, Thalidomide, and Dexamethasone With or Without Cyclophosphamide As Induction Therapy in Previously Untreated Multiple Myeloma
Abstract
Purpose: Bortezomib-thalidomide-dexamethasone (VTD) is an effective induction therapy in multiple myeloma (MM). This phase II, noncomparative study sought to determine whether addition of cyclophosphamide to this regimen (VTDC) could further increase efficacy without compromising safety.
Results: Postinduction, 51% (VTD) and 44% (VTDC) of patients achieved combined CR/nCR, with bone marrow-confirmed CR in 29% and 31%, overall response rates of 100% and 96%, respectively, and very good partial response or better rates of 69% per arm. Post-HDCT-ASCT, combined CR/nCR rates were 85% (VTD) and 77% (VTDC).
In all, 35% (VTD) and 27% (VTDC) of patients were negative for minimal residual disease (MRD) during induction and postinduction. Three-year overall survival was 80% (both arms).
Grade 3 to 4 adverse events (AEs) and serious AEs were observed in 47% and 22% (VTD) and 57% and 41% (VTDC) of patients, respectively. The primary health-related quality of life end point (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 [EORTC QLQ-C30] Global Health score) steadily increased with VTD during induction and reached a clinically relevant difference post-transplantation versus baseline.
Conclusion: Both VTD and VTDC are highly active induction regimens producing high combined CR/nCR and MRD-negative rates; however, VTDC was associated with increased toxicity and suggestion of transient decreases in Global Health score, without an increase in activity.