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Antonio Palumbo, MD1, Patrizia Falco, MD, Francesca Gay, MD, Vittorio Montefusco, MD, Claudia Crippa, MD, Francesca Patriarca, MD, Milena Gilestro, PhD, Anna M. Liberati, MD, Fausto Rossini, MD, Tommaso Caravita, MD, Antonietta Falcone, MD, Federica Cavallo, MD, Paolo Corradini, MD, Giuseppe Rossi, MD and Mario Boccadoro, MD

Background: New agents have been introduced as induction prior to autologous stem cell transplant (ASCT) and as consolidation/maintenance thereafter to improve complete response (CR) rates. In this trial we evaluate Bortezomib plus Pegylated-lyposomal-doxorubicin and Dexamethasone (PAD) as induction therapy prior to reduced intensity ASCT, followed by consolidation with Lenalidomide and Prednisone (LP) and maintenance with Lenalidomide alone (L).

Methods: Newly diagnosed multiple myeloma (MM) patients aged 65-75 years were eligible. Induction regimen consisted of 4 21-day PAD cycles (Bortezomib 1.3 mg/m2 days 1, 4, 8, 11, Pegylated-lyposomal-doxorubicin 30 mg/m2 day 4 and Dexamethasone 40 mg days 1-4, 8-11, 15-18). Two cycles of Cyclophosphamide 3 g/m2 plus Granulocyte-Colony Stimulating Factor were used to harvest stem cells. Patients were conditioned with tandem Melphalan 100 mg/m2 (MEL100) followed by stem cell support. After ASCT patients received consolidation with 4 28-day LP cycles (Lenalidomide 25 mg days 1-21 plus, Prednisone 50 mg every other day) followed by Lenalidomide alone maintenance (10 mg days 1-21 every 28 day). Primary objectives were safety (grade 3 non-hematologic toxicity < 30%) and efficacy (near CR rate > 35%).

Results: One-hundred and two patients have been enrolled. After PAD cycles at least partial response (PR) rate was 94%, at least very good partial response (VGPR) was 59% including 13% CR. After tandem MEL100, 88% of patients achieved at least VGPR and 41% CR. After LP consolidation all patients obtained PR, 88% at least VGPR and 53% immunofixation negative CR. After a median follow-up of 14 months, 1-year progression free survival (PFS) was 92%, 1 year time to progression was 97% and 1 year overall survival was 92%. PFS was not significantly affected β2-microglobulin levels (p=0.10), presence of chromosome 13 deletion (p=0.5) or t(4;14) (p=0.61).

During PAD, grade 3-4 adverse events included thrombocitopenia (13%), neutropenia (11%), infections (18%), gastrointestinal toxicities (12%), peripheral neuropathy (11%) and deep vein thrombosis (6%). During LP consolidation, grade 3-4 toxicities included neutropenia (18%), thrombocytopenia (6%), infections (6%) and deep vein thrombosis (6%). The other grade 3-4 toxicities occurred in less than 5% of patients.

Conclusions: Bortezomib as induction regimen prior to reduced intensity ASCT, followed by Lenalidomide as consolidation maintenance is a highly effective regimen in elderly patients. Updated results will be presented at the meeting.