Multiple Myeloma

Phase III trial of bortezomib, cyclophosphamide and dexamethasone (VCD) versus bortezomib, doxorubicin and dexamethasone (PAd) in newly diagnosed myeloma

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Abstract

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 (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.

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Acknowledgements

We thank the investigators, the study nurses and all the members of the study teams at the participating GMMG trial sites, the teams of the myeloma research laboratory, the FISH laboratory and the central laboratory at the University Hospital Heidelberg, the coordination centers for clinical trials (KKS) in Heidelberg and Leipzig, the pharmacies at the trial sites and, most importantly, the participating patients and their families. This study was supported by grants from Celgene, Janssen-Cilag, Chugai and Binding Site.

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Correspondence to H Goldschmidt.

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Competing interests

EKM received travel grants from Janssen-Cilag, Celgene, Onyx and Mundipharma. JD received honoraria from Janssen-Cilag, Celgene, Roche and GSK, and compensation for his consulting/advisory roles for Janssen-Cilag, Roche and GSK. MMu received honoraria from Celgene as well as travel grants from Mundipharma and Celgene. DH received compensation for his consulting/advisory role from Celgene and also received research funding from Novartis and Celgene. JH received honoraria from Celgene and Janssen-Cilag. IGHS-W received compensation for his consulting/advisroy role from Janssen-Cilag. KW received honoraria from Celgene, Janssen-Cilag and Onyx; received compensation for her consulting/advisory role at Celgene, Janssen, Onyx and Noxxon; and also received research funding from Celgene and travel grants from Celgene and Janssen-Cilag. CS received honoraria and compensation for his consulting/advisory role from Janssen-Cilag and Celgene. HS received honoraria from Celgene, Janssen-Cilag, Chugai, Novartis, Mundipharma, TEVA, Roche, Binding Site and BMS; received compensation for his consulting/advisory role at Celgene, Janssen-Cilag, BMS, Novartis and TEVA; received research funding from Celgene, Janssen-Cilag, Novartis and BMS; and also received travel grants from Celgene, Janssen-Cilag, Novartis, TEVA and Roche. HG received honoraria from Janssen-Cilag, Celgene, Novartis, Onyx and Millennium; has a consulting/advisory role at Janssen-Cilag, Celgene, Novartis, Onyx and Millennium; received compensation as a member of the speakers bureau from Janssen-Cilag, Celgene, Novartis, Onyx, Millennium and Chugai; and also received research funding from Janssen-Cilag, Celgene, Novartis and Chugai. UB, CK, MH, IWB, AJ, BS, TH, MMe, BH-D, AS, MSR, KN, H-WL, MZ and CG declare no conflict of interest.

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Mai, E., Bertsch, U., Dürig, J. et al. Phase III trial of bortezomib, cyclophosphamide and dexamethasone (VCD) versus bortezomib, doxorubicin and dexamethasone (PAd) in newly diagnosed myeloma. Leukemia 29, 1721–1729 (2015) doi:10.1038/leu.2015.80

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