Long-term Follow-up of MRC Myeloma IX Trial: Survival Outcomes with Bisphosphonate and Thalidomide Treatment

Abstract

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 ¼ 1,970) were assigned to bisphosphonate (clodronic acid or zoledronic acid) and induction therapies [cyclophosphamide-vincristine-doxorubicindexamethasone (CVAD) or cyclophosphamide-thalidomide-dexamethasone (CTD) followed by highdose 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 ¼ 0.02) and overall survival (OS; HR, 0.86; P ¼ 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 ¼ 0.068). In the nonintensive pathway, CTDa significantly improved PFS (HR, 0.81; P ¼ 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 ¼ 0.70), and was associated with shorter OS in patients with adverse cytogenics (P ¼ 0.01).Conclusions: Long-term follow-up is essential to identify clinically meaningful treatment effects in myeloma subgroups based on cytogenetics.

A myeloma multiplex megközelítése Magyarországon 2016-ban

“…A fenti protokollokat a 4. táblázat foglalja össze [37][38][39][43][44][45][46][47][48][49][50][51][52][53][54][55].…”

“…Nagy vizsgálatokból származó evidencia szól amellett, hogy az iv. zoledronat per os clodronattal összehasonlít-va nemcsak szignifikánsan csökkentette a csonttörések gyakoriságát, hanem 6 hónapos túlélési előnyt is jelentett [46]. A kezelés legfontosabb szövődménye az osteonecrosis (ONJ), de ennek gyakorisága megfelelő betegoktatással és a kezelés megindítása előtti kötelező fogászati szűréssel csökkenthető.…”

Consolidation and maintenance therapy for multiple myeloma after autologous transplantation: where do we stand?

“…Of note, in three of the studies, survival after relapse was found to be reduced following thalidomide exposure. 3,[29][30][31] Abbreviations: EFS = event-free survival; HDM = high-dose melphalan; OS = overall survival; PAD = bortezomib-doxorubicin-dexamethasone; Thal = thalidomide; VAD = vincristine-doxorubicin-dexamethasone; VT = bortezomib-dexamethasone. a With longer follow-up, the survival advantage disappeared in the IFM study, but it emerged in the study by Barlogie et al 29 Consolidation and maintenance therapy for multiple myeloma M Mohty et al…”

“…In addition, Morgan et al 30,31 observed that in patients with adverse-risk cytogenetics, thalidomide maintenance resulted in shorter OS. In a recently reported final analysis of a study conducted by the Australian myeloma group (with a median follow-up 5.4 years), thalidomide administered in combination with prednisolone for 1 year was found to significantly prolong PFS and OS compared with prednisolone alone: 5-year PFS was 27% for Thal/Pred versus 15% for Pred, P = 0.005; 5-year OS was 66% versus 47%, respectively, P = 0.007).…”

Maintenance Therapy for Multiple Myeloma

“…Four Phase III studies studied thalidomide maintenance until progression 32,[45][46][47][48] . (Table 2) The Intergroupe Francophone du Myelome (IFM) randomized 400 patients after AHSCT to thalidomide versus no maintenance and demonstrated an improved 3-year EFS (52% versus 37%, P<0.009) and an improved 4 year OS (87% versus 75%, P<0.04) 32 .…”