Autologous Transplantation for Myeloma: Induction, Mobilization, and Biologic Correlates
VELCADE/Dexamethasone (Vel/D) Versus VAD as Induction Treatment Prior to Autologous Stem Cell Transplantion (ASCT) in Newly Diagnosed Multiple Myeloma (MM): Updated Results of the IFM 2005/01 Trial.
Jean Luc Harousseau, MD1,
Claire Mathiot, MD2,*,
Michel Attal, MD2,
Gerald Marit, MD2,*,
Denis Caillot, MD2,*,
Mohamad M.M. Mohty, MD2,
Cyrille Hullin, MD2,*,
Thierry T.F. Facon, MD2,
Iain I.W. Webb, MD3 and
Philippe Moreau, MD2
1 Hematology, University Hospital, Nantes, France; 2 Hematology, Intergroupe Francophone du Myelome, Paris Curie, France and 3 Millenium Pharmaceuticals, Cambridge, USA.
Introduction. ASCT is considered the standard of care for youngerpatients (pts) with MM. The benefit of ASCT is at least partlyrelated to an increase in Complete Remission (CR) plus VeryGood Partial Remission (VGPR) rate. One way to increase theCR rate is to improve the induction treatment prior to ASCT.Several phase II studies with Vel in combination as inductiontreatment yielded promising CR rates. We have previously testedthe Vel/D combination with Vel 1.3mg/m2 d1,4,8,11 with 40mg/dd1–4, d 9–12 for 4 consecutive 21d cycles (D onlyon d1–4 during cycles 3–4) (Harousseau et al Haematologica2006).
Methods. In July 2005, the IFM initiated a randomized PhaseII trial comparing Vel/D with VAD as induction treatment priorto ASCT in pts with newly diagnosed MM up to the age of 65.ThisIFM 2005/01 was closed for accrual in January 2007 after havingrecruited 482 patients. The primary objective was the CR (negativeimmunofixation) plus n-CR (negative electrophoresis) after 4cycles. The second question was to evaluate the impact of aconsolidation with 2 cycles of DCEP (D, Cyclophosphamide, Etoposide,Platinum). At diagnosis pts were randomized between 4 arms (A1:4cycles of VAD, A2: 4 cycles of VAD + 2 cycles of DCEP, A3:4cycles of Vel/D, A4:4 cycles of Vel/D + 2 cycles of DCEP). Randomizationwas stratified according to β2-microglobulin and del 13by FISH analysis. Stem cell collection was performed betweencycle 3 and 4 after G-CSF priming (10µg/kg x 6d). ASCTwas prepared by melphalan 200mg/m2.
Results. As of Aug 2007, data from the first consecutively enrolled222 pts have been analyzed (A1:54,A2:56,B1:55,B2:57). In theVAD arms (A1+A2),88% of pts received the planned 4 courses versus94% in the Vel/D arms (B1+B2). In arm A2,87.5% of pts receivedthe 2 cycles of DCEP versus 82% in arm B2. ASCT was performedin 94% of evaluable pts in arms A1+A2 and in 92% in arms B1+B2.The number of SAE was the same in the VAD and the Vel/D arms.The incidence of grade 3–4 averse events was also comparable.However the proportion of pts with neurological symptoms (allgrades) during induction treatment was higher with Vel/D (36%versus 11%). Response assessment is available for 208 pts (100VAD, 108 Vel/D). The results are shown in the table (intent-to-treatanalysis). Consolidation with DCEP did not increase the CR rate(16% pre-ASCT both in arms A1+B1 and in arms A2+B2).
Conclusion. This analysis not only confirms that the post-inductionCR rate is increased by Vel/D compared to VAD (Harousseau ASH2006) but also shows that this benefit translates in higherCR+VGPR rates after ASCT. Longer follow-up is needed to demonstratethat this better tumor reduction induces longer PFS and OS.Currently 1-year PFS and OS rates are respectively 90% and 95%with VAD, 93% and 97% with Vel/D. Updated results will be presentedat the meeting.
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