A105 A Phase III Study of MEL200 Versus MEL100 in Newly Diagnosed Myeloma Young Patients

Introduction and Aims: New agents have been introduced as induction prior to autologous stem cell transplantation (ASCT) and as consolidation/maintenance thereafter to improve complete response (CR) rates. We evaluate bortezomib plus pegylatedlyposomal-doxorubicin and dexamethasone (PAD) as induction prior to reduced intensity ASCT, followed by consolidation with lenalidomide and prednisone (LP) and maintenance with lenalidomide alone (L). Materials and Methods: Newly diagnosed multiple myeloma patients aged 65-75 years were eligible. Induction consisted of four 21-day PAD cycles (bortezomib 1.3 mg/m2 days 1, 4, 8, 11; pegylated-lyposomal-doxorubicin 30 mg/m2 day 4; dexamethasone 40 mg days 1-4, 8-11, and 15-18). Patients were conditioned with tandem melphalan 100 mg/m2 (MEL100) followed by stem cell support. After ASCT patients received consolidation with four 28-day LP cycles (lenalidomide 25 mg days 1-21, prednisone 50 mg every other day) followed by lenalidomide maintenance (10 mg days 1-21). Primary objectives were safety (grade 3 nonhematologic toxicity 35%). Results: One-hundred and two patients entered the study. After PAD, 94% of patients achieved at least partial response (PR) and 59% at least very good partial response (VGPR) including 13% CR. After tandem MEL100, 88% of patients obtained at least VGPR and 41% CR. After LP all patients achieved PR, 88% at least VGPR including 53% CR. After a median follow-up of 14 months, 1-year progression-free survival (PFS) was 92%, and 1-year overall survival was 92%. PFS was not significantly affected by b2-microglobulin levels (P = .10), presence of chromosome 13 deletion (P = .5) or t(4;14)(P = .61). During PAD, grade 3/4 adverse events included thrombocytopenia (13%), neutropenia (11%), infections (18%), gastrointestinal toxicities (12%), peripheral neuropathy (11%) and deep vein thrombosis (DVT) (6%). During LP, grade 3/4 toxicities included neutropenia (18%), thrombocytopenia (6%), infections (6%) and DVT (6%). The other grade 3/4 toxicities occurred in less than 5% of patients. Conclusion: Bortezomib as induction, followed by lenalidomide as consolidation/maintenance is a highly effective regimen in elderly patients. Updated results will be presented at the meeting.