This is an interim analysis of 420 of the 480 patients enrolled in the IFM 2005-01 trial of induction and consolidation therapies prior to SCT. The overall response rate is thus far 82% for Vel/dex and 65% for VAD. The secondary objective, to evaluated consolidation, demonstrates that consolidation therapy with DCEP after VAD or Velcade/dex increases the response rate but is toxic and is therefore refused or not tolerated by patients.
VELCADE/Dexamethasone (Vel/Dex) Versus VAD as Induction Treatment Prior to Autologous Stem Cell Transplantation (ASCT) in Newly Diagnosed Multiple Myeloma (MM): An Interim Analysis of the IFM 2005-01 Randomized Multicenter Phase III Trial. Session Type: Oral Session
Jean-Luc Harousseau, Gerald Marit, Denis Caillot, Philippe Casassus, Thierry Facon, Mohamad Mohty, Frederic Maloisel, Herve Maisonneuve, Carine Chaleteix, Lofti Benboubker, Dixie-Lee Esseltine, Michel Attal Hematology, Hpital Hotel-Dieu, Nantes, France; CHU Bordeaux, Pessac, Bordeaux, France; Hematology Unit, Hpital Bocage, Dijon, France; Hpital Avicenne, Bobigny, Paris, France; Hpital Claude-Huriez, Lille, France; Institute Paoli-Calmettes, Marseille, France; Hpital Civil, Strasbourg, France; CHD La Roche Sur Yon, La Roche Sur Yon, Vendee, France; CHU Clermont-Ferrand, Clermont-Ferrand, Auvergne, France; Hematology and Cell Therapy Unit, CHRU Tours, Tours, France; Millennium Pharmaceuticals Inc, Cambridge, MA, USA; Hpital Purpan, Toulouse, France
ASCT is considered the standard of care for patients up to 65 years of age with MM. The optimal induction treatment prior to ASCT is still unknown. VAD is a commonly used regimen but is associated with a number of toxicities, administrative inconvenience, and a complete remission (CR) rate of typically less than 10%. Recently the combination thalidomide/Dex was reported to induce a higher overall response rate than Dex alone in newly diagnosed patients, but with significantly more toxicities, especially deep vein thrombosis, and a 4% CR rate (Rajkumar et al, J Clin Oncol 2006;24:4316). In a phase II trial we have evaluated the combination of Vel 1.3mg/m2 D1, 4, 8, 11 with Dex 40mg/D D14, D912, for 4 consecutive 21-D cycles (Dex only on D14 during cycles 34). This combination was well tolerated and yielded a 21% CR/nCR rate with successful stem cell harvest and engraftment (Harousseau et al, Haematologica 2006). In 2005, the IFM initiated a multicenter randomized phase III trial comparing Vel/Dex with VAD as induction treatment of patients with newly diagnosed MM up to the age of 65. The primary objective of the study is the CR (negative immunofixation) plus nCR (CR but positive immunofixation) rate after 4 cycles. A secondary objective is to evaluate the role of consolidation with 2 courses of DCEP (Dex, cyclophosphamide, etoposide, cisplatin). Patients were randomized at diagnosis among 4 arms (A1: 4 cycles of VAD; A2: 4 cycles of VAD + 2 cycles of DCEP; B1: 4 cycles of Vel/Dex; B2: 4 cycles of Vel/Dex + 2 cycles of DCEP); stratification was by cytogenetics and 2 microglobulin. Stem cell collection was performed between cycle 3 and cycle 4 after priming with G-CSF (10g/kg/D x 6 D). At the end of induction ( DCEP consolidation) treatment, patients received melphalan 200mg/m2 plus ASCT. Enrollment of 480 patients is planned, to detect a 10% higher CR/nCR rate with Vel/Dex (20% vs 10%) with 80% power (two-sided test, significance level 0.05). An interim analysis is planned when 222 patients have been evaluated for response at the end of induction. As of July 2006, 304 patients have been enrolled. Randomization of the 222 patients to be considered for interim analysis was completed on May 19th. Baseline characteristics include: median age 55y; 140M, 82F; 2 microglobulin >3mg/L in 54%; del13 by FISH in 45%. The occurrence of serious adverse events (SAEs) was similar between the VAD and Vel/Dex arms (31% with VAD, 33% with Vel/Dex). The most frequent SAEs were pneumopathy (5.3% VAD, 4.0% Vel/Dex), thrombosis (2.7% VAD, 3.3% Vel/Dex), and peripheral neuropathy (1.3% VAD, 3.3% Vel/Dex). We intend to present results from the interim analysis.
Abstract #56 appears in Blood, Volume 108, issue 11, November 16, 2006