PURPOSE: Medical Research Council (MRC) Myeloma IX was a phase III trial evaluating bisphosphonate and thalidomide-based therapy for newly diagnosed multiple myeloma. Results were reported previously after a median follow-up of 3.7 years (current controlled trials number: ISRCTN68454111). Survival outcomes were reanalyzed after an extended follow-up (median, 5.9 years). EXPERIMENTAL DESIGN: At first randomization, patients (N = 1,970) were assigned to bisphosphonate (clodronic acid or zoledronic acid) and induction therapies [cyclophosphamide-vincristine-doxorubicin-dexamethasone (CVAD) or cyclophosphamide-thalidomide-dexamethasone (CTD) followed by high-dose therapy plus autologous stem cell transplantation for younger/fitter patients (intensive pathway), and melphalan-prednisone (MP) or attenuated CTD (CTDa) for older/less fit patients (nonintensive pathway)]. At second randomization, patients were assigned to thalidomide maintenance therapy or no maintenance. Interphase FISH (iFISH) was used to analyze cytogenics. RESULTS: Zoledronic acid significantly improved progression-free survival (PFS; HR, 0.89; P = 0.02) and overall survival (OS; HR, 0.86; P = 0.01) compared with clodronic acid. In the intensive pathway, CTD showed noninferior PFS and OS compared with CVAD, with a trend toward improved OS in patients with favorable cytogenics (P = 0.068). In the nonintensive pathway, CTDa significantly improved PFS (HR, 0.81; P = 0.007) compared with MP and there was an emergent survival benefit after 18 to 24 months. Thalidomide maintenance improved PFS (HR, 1.44; P < 0.0001) but not OS (HR, 0.96; P = 0.70), and was associated with shorter OS in patients with adverse cytogenics (P = 0.01). CONCLUSIONS: Long-term follow-up is essential to identify clinically meaningful treatment effects in myeloma subgroups based on cytogenetics.
PURPOSE: Medical Research Council (MRC) Myeloma IX was a phase III trial evaluating bisphosphonate and thalidomide-based therapy for newly diagnosed multiple myeloma. Results were reported previously after a median follow-up of 3.7 years (current controlled trials number: ISRCTN68454111). Survival outcomes were reanalyzed after an extended follow-up (median, 5.9 years). EXPERIMENTAL DESIGN: At first randomization, patients (N = 1,970) were assigned to bisphosphonate (clodronic acid or zoledronic acid) and induction therapies [cyclophosphamide-vincristine-doxorubicin-dexamethasone (CVAD) or cyclophosphamide-thalidomide-dexamethasone (CTD) followed by high-dose therapy plus autologous stem cell transplantation for younger/fitter patients (intensive pathway), and melphalan-prednisone (MP) or attenuated CTD (CTDa) for older/less fit patients (nonintensive pathway)]. At second randomization, patients were assigned to thalidomide maintenance therapy or no maintenance. Interphase FISH (iFISH) was used to analyze cytogenics. RESULTS: Zoledronic acid significantly improved progression-free survival (PFS; HR, 0.89; P = 0.02) and overall survival (OS; HR, 0.86; P = 0.01) compared with clodronic acid. In the intensive pathway, CTD showed noninferior PFS and OS compared with CVAD, with a trend toward improved OS in patients with favorable cytogenics (P = 0.068). In the nonintensive pathway, CTDa significantly improved PFS (HR, 0.81; P = 0.007) compared with MP and there was an emergent survival benefit after 18 to 24 months. Thalidomide maintenance improved PFS (HR, 1.44; P < 0.0001) but not OS (HR, 0.96; P = 0.70), and was associated with shorter OS in patients with adverse cytogenics (P = 0.01). CONCLUSIONS: Long-term follow-up is essential to identify clinically meaningful treatment effects in myeloma subgroups based on cytogenetics.
Authors: Heinz Ludwig; Pieter Sonneveld; Faith Davies; Joan Bladé; Mario Boccadoro; Michele Cavo; Gareth Morgan; Javier de la Rubia; Michel Delforge; Meletios Dimopoulos; Hermann Einsele; Thierry Facon; Hartmut Goldschmidt; Philippe Moreau; Hareth Nahi; Torben Plesner; Jesús San-Miguel; Roman Hajek; Pia Sondergeld; Antonio Palumbo Journal: Oncologist Date: 2014-07-25
Authors: Francesca Gay; Graham Jackson; Laura Rosiñol; Sarah A Holstein; Philippe Moreau; Stefano Spada; Faith Davies; Juan José Lahuerta; Xavier Leleu; Sara Bringhen; Andrea Evangelista; Cyrille Hulin; Ugo Panzani; David A Cairns; Francesco Di Raimondo; Margaret Macro; Anna Marina Liberati; Charlotte Pawlyn; Massimo Offidani; Andrew Spencer; Roman Hájek; Evangelos Terpos; Gareth J Morgan; Joan Bladé; Pieter Sonneveld; Jesús San-Miguel; Philip L McCarthy; Heinz Ludwig; Mario Boccadoro; Maria-Victoria Mateos; Michel Attal Journal: JAMA Oncol Date: 2018-10-01 Impact factor: 31.777
Authors: R Chakraborty; E Muchtar; S K Kumar; F K Buadi; D Dingli; A Dispenzieri; S R Hayman; W J Hogan; P Kapoor; M Q Lacy; N Leung; R Warsame; T Kourelis; W Gonsalves; M A Gertz Journal: Leukemia Date: 2017-08-14 Impact factor: 11.528