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Abstract 349 We report here on the final analysis of the multicenter phase II “Bologna 2002” study which incorporated thal-dex into double ASCT with high-dose melphalan (200 mg/m2) as front-line therapy for younger patients with symptomatic multiple myeloma (MM). By study design, thal (200 mg/day) and pulsed low-dose dex (160 mg/month, with two added 4-day courses on the first and third cycle of induction therapy) were administered from the outset until the second ASCT. The analysis was performed on an intention-to-treat basis on a total of 357 patients who were followed for a median of 43 months. Their median age was 57 years, 86% had advanced disease stage. More than 80% of the patients were screened at diagnosis for the presence of cytogenetic abnormalities (FISH) on CD138+ bone marrow plasma cells, including del(13q) (45%), t(4;14) (14%) and del(17p) (6%). The rate of at least VGPR increased from 31% after thal-dex induction therapy to 60% after the second ASCT. The final CR rate was 33% for all the patients and 44% for those who actually received pre planned double ASCT. Median TTP and PFS were 68 and 47 months, respectively, with 5-year projected rates of 45% and 33%. The 5-year projected OS rate was 65%. TRM after the first and second ASCT was 0.5% and 2%, respectively. Median OS after relapse or progression was 30 months, suggesting that short-term thal exposure had no adverse influence on response to salvage therapies. The quality of response following ASCT(s) influenced clinical outcomes. In particular, patients achieving CR had significantly longer PFS and OS than patients in VGPR (PFS: median 68 vs 48 months, respectively, P=0.04; 5-year projected OS 84% vs 72%, respectively, P=0.02). Similarly, patients in VGPR had better outcomes compared with patients achieving PR (P=0.02 and 0.04 for PFS and OS comparisons, respectively). In a multivariate analysis, best response (at least VGPR) ever achieved and low beta2-m were the most important variables significantly extending TTP (P=0.04), PFS (P=0.000) and OS (P=0.003). Additional variables predicting for prolonged PFS were the absence of del(13q) (P=0.002) and del(17p) with or without t(4;14)(P=0.03). OS was favourably influenced also by IgG isotype (P=0.04) and absence of high-risk cytogenetic abnormalities [del (17p) +/- t(4;14)(P=0.03)]. A case match comparison of 135 patients enrolled in “Bologna 2002” study with an equal number of pair mates included in the previous “Bologna 96” study of double ASCT without thal confirmed the benefits from the addition of thal-dex to double autotransplantation in terms of rate (P=0.001) and duration (p Disclosures: Off Label Use: Thalidomide was incorporated into up-front treatment for patients with newly diagnosed multiple myeloma.

Wide experience have been reported on vertebroplasty in multiple myeloma patients. Much less experience is available for the treatment of osteolytic lesions in other critical sites. The aim of this report is to evaluate feasibility, safety and efficacy of transcutaneous femoroplasty, ileoplasty and sacroplasty in advanced multiple myeloma patients with severe osteolytic lesions. From November 2004 to May 2008 8 consecutive advanced myeloma patients (3 males and 5 females, median age 75 years, range 50–78) with pelvis and femora bone lytic lesions entered the study. They received percutaneous bone-cement injection with a solution of 8 to 22 polymethylmethacrylate (PMMA) into supracetabular (4 cases), sacral (2 cases) and femoral bone cavities (2 cases). Lesion approach was performed by 10 g bone biopsy needle under Computed Tomography (CT) and fluoroscopic guidance. In two cases, characterized by large extraosseous lesions, tumour termoablation with radiofrequency was done before PMMA injection. Procedures were performed under local anaesthesia, conscious sedation and antibiotic profilaxis with intravenous ceftriaxone in all patients. Immediate complications were studied with post procedure CT control. Efficacy was evaluated in term of pain relief and mobility recovery. Pain and mobility were assessed by visual analogue scale score (VAS) system (grading 0–10) and functional mobility score system (grading 1–4) respectively (according with “CT-guided percutaneous vertebroplasty: personal experience in the treatment of osteoporotic fractures and dorsolumbar metastases” Radiol med (2008) 113:114–133). Evaluation was performed before and at determined time points after the procedure (at 24 hours, one week, one month and every 3 months). Technical success was achieved in all patients. No complication was recorded. Before the osteoplasty pain assessment by VAS score showed a median value of 6 (range 4–8) and all patients were on analgesic therapy with oppioids and NSAIDs before the procedure. The VAS score decreased to median value 0 (range 0–1.5) within 24 hours after the procedure. The score remained unmodified during the rest of follow-up (median 17.5 months range 2–43). Seven patients were pain free (VAS score 0). Persistence of mild pain was documented in a single patient (score 1,5). Functional mobility score before osteoplasty was 4 in all patients (all were unable to autonomous deambulation). Score became 1 in all (autonomous mobility) within one week after procedure and remained stable during the follow up. Percutaneous osteoplasty is a feasible and safe procedure in patients affected by multiple myeloma with pelvis and femora osteolytic painful lesions. The methylmetacrylate injection is a minimally invasive procedure providing immediate improvement of quality of life. This intervention can contribute to treatment of the multiple myeloma in association with conventional therapy.

The phase II “Bologna 2002” clinical study incorporated thalidomide-dexamethasone (thal-dex) into double ASCT with melphalan (200 mg/m2) as frontline therapy for patients with symptomatic multiple myeloma (MM) and less than 65 years of age. By study design, thal (200 mg/d) and dex (40 mg/d x 4d every month, with two added courses on the 1st and 3rd month of therapy) were administered from the outset until the second ASCT. An analysis was performed on 311 consecutive patients who entered the study from January 2002 to March 2006 and were followed for a median of 32 months. On an intention-to-treat (ITT) basis, the ≥ very good partial response (VGPR) rate increased from 29% after 4 months of primary induction therapy with thal-dex to 63% after the second ASCT. Transplantation-related mortality after first and second ASCT was 1% and 3%, respectively. Median durations of relapse-free survival (RFS) and event-free survival (EFS) were 52 and 42 months, respectively. The 5-year projected overall survival (OS) rate was 70%. A case-match comparison of 135 of these patients with an equal number of pair mates who entered the “Bologna 96” study and were randomly assigned to receive double ASCT without thal showed significant benefit from incorporation of thal into double ASCT in terms of increased ≥VGPR rate (68% vs 49%, respectively; P=0.001) and extended RFS (54% vs 32% at 5 years; P=0.005) and EFS (median: 52 vs 33 months; P=0.01). All 311 patients were screened on purified CD138+ bone marrow plasma cells for the presence at diagnosis of chromosome 13 alterations [del(13)] (47% of cases) and t(4;14) (13% of cases). In a logistic regression analysis, neither del(13) nor t(4;14) adversely influenced response (≥VGPR) to primary induction therapy with thal-dex. At the opposite, both absence of del(13) (P=0.001) and low beta2- microglobulin (beta2-m) levels (P=0.007) were significantly related to attainment of ≥VGPR after the second ASCT. In a multivariate analysis of all 311 patients, the most important variable significantly extending time to progression (TTP), EFS and OS was the absence of del(13) (P=0.001, P=0.001 and P=0.007, respectively), along with attainment of ≥VGPR after the second ASCT. OS was also significantly influenced by both beta2-m (P=0.044) and hemoglobin (Hb) concentration (P=0.05), whereas platelet count was an additional prognostic factor for TTP (P=0.025). In conclusion, in comparison with double ASCT, incorporation of thal into double ASCT as up-front therapy for MM significantly improved the response rate (≥ VGPR), RFS and EFS, without adversely affecting postrelapse OS. The presence of del(13) by FISH analysis was the most important and independent variable adversely influencing attainment of ≥ VGPR, EFS and OS following thal-dex and double ASCT.