ALBERT

Description: Energy & Fuels DOI: 10.1021/acs.energyfuels.7b01674

Description: Abstract 2877 Poster Board II-853 Background and Objective: In newly diagnosed multiple myeloma (MM) patients, treatment with lenalidomide plus high-dose dexamethasone (RD) was superior to high-dose dexamethasone in terms of both response rates and 1-year progression-free survival (PFS) (Zonder JA et al, Blood 2007;110:77). Preliminary results suggest that the combination lenalidomide plus low-dose dexamethasone (Rd) compared to the RD regimen yields significantly better 2-year overall survival (OS) (Rajkumar SV et al, J Clin Oncol 2008;26:8504). The combination of melphalan, prednisone, and lenalidomide (MPR) has been investigated in a phase I/II study showing promising results (Palumbo A et al, J Clin Oncol 2007; 25:4459-4465). The goal of this case –control study was to compare the efficacy and the toxicity of the lenalidomide/dexamethasone (len/dex) combination vs MPR as primary therapy for newly diagnosed elderly MM patients, to determine the additive value of melphalan compared to a regimen of lenalidomide plus corticosteroid. Patients and methods: Data from 51 newly diagnosed MM patients enrolled in Italy in a phase I/II dose-escalating trial, from January to October 2005, with MPR, were analyzed. For comparison of their outcome, 37 patients were identified among newly diagnosed patients seen at the Mayo Clinic from March 2005 to December 2008 who received len/dex as primary therapy and were enrolled in phase II or III trials. Patients treated with MPR received 9 monthly cycles of oral melphalan (doses ranging from 0.18 to 0.25 mg/kg on days 1-4), prednisone (2 mg/kg on days 1-4) and lenalidomide (doses ranging from 5 to 10 mg/day on days 1-21). After 9 cycles, patients started maintenance with lenalidomide alone (10 mg, days 1-21) until relapse or progression. Patients treated with len/dex received oral lenalidomide (25 mg/day, days 1-21) plus dexamethasone, either at low-dose (n=17) (40 mg orally days 1, 8, 15, 22) or at high-dose (n=21) (40 mg orally on days 1-4, 9-12, and 17-20). Treatment was continued until progression, relapse or unacceptable toxicity, or could be stopped at the physician's discretion. Patients (n=13) were allowed to receive transplant if they wished and were deemed eligible. Outcome was analyzed on an intention-to-treat basis. The Chi-square or the rank sum tests were used to compare variables. Time-to-event analysis was performed using the Kaplan-Meier method and comparisons were determined by the log-rank test and the Cox proportional hazards model. Results: On intention-to-treat analysis, 15.7% versus 23.7% patients, respectively in the MPR and in the len/dex group, (p=0.342) achieved a complete response, and 43.2% vs 47.4%, (p=0.691) achieved at least a very good partial response. Time-to-progression (TTP) (median: 24.7 vs 27.5 in MPR and len/dex groups, respectively; HR 1.04; 95% CI 0.55-1.98; p=0.903), PFS (median: 24.7 vs 27.5 in MPR and len/dex groups, respectively; HR 1.03; 95% CI 0.55-1.92; p=0.926) and OS (2-year OS: 86.2% in MPR group vs 89.1% in len/dex, HR 0.86; 95% CI 0.38-1.98; p=0.730) were not significantly different between the 2 groups. No significant differences in TTP, PFS and OS were reported when MPR patients were compared with the subgroup of patients treated with low-dose dexamethasone plus lenalidomide. Similar results were found when the analysis was restricted to MPR patients and len/dex pair mates receiving lenalidomide plus low/dose dexamethasone, matched according to age and sex, and who did not received transplant. The toxicity profile was different in the two groups. Hematologic grade 3-4 toxicities were more common with MPR compared with len/dex, in particular neutropenia (66.7% vs 21.1%, p 〈 0.001) and thrombocytopenia (31.4% vs 2.6%, p 〈 0.001), respectively. Grade 3-4 gastrointestinal events (13.2% vs 2.0%, p= 0.080), thrombotic events (13.2 vs 5.9, p= 0.279) and fatigue (10.5% vs 3.9%, p= 0.395) were more common with len/dex compared with MPR. Conclusion: Results of this case-control study show that both MPR and Rd are efficacious regimens for elderly MM patients. Data need however to be carefully evaluated and randomized control trials are needed to confirm these results. Disclosures: Off Label Use: research drug in combination to standard of care. Kumar:celgene: Research Funding; millenium: Research Funding; bayer: Research Funding; novartis: Research Funding; genzyme: Research Funding. Dispenzieri:celgene: Research Funding. Gertz:celgene: Honoraria; genzyme: Honoraria; millenium: Honoraria; amgen: Honoraria. Lacy:celgene: Research Funding. Musto:celgene: Honoraria. Fonseca:medtronic: Consultancy; genzyme: Consultancy; celgene: Consultancy; amgen: Consultancy; BMS: Consultancy; otsuka: Consultancy. Petrucci:celgene: Honoraria; Janssen Cilag: Honoraria. Greipp:celgene: Research Funding. Boccadoro:jansen Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; pharmion: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Palumbo:Janssen-Cilag: Honoraria; Celgene: Honoraria.

Description: In newly diagnosed multiple myeloma (MM) patients, the combination melphalan, prednisone and thalidomide induces a fast tumor response with a high complete remission rate. In a prospective randomized trial, we compare the efficacy and toxicity of oral MPT and MP. An interim analysis was conducted after the first 200 newly diagnosed myeloma patients, median age 72, range 56–85, entered the study, between January 2002 and June 2004. At present, 116 patients were evaluated for toxicity and 102 patients for response on an intent to treat basis. The MPT regimen included 6 monthly courses of oral melphalan 4 mg/sqm and prednisone 40 mg/sqm for 7 days every month plus thalidomide 100 mg/day continuously until any sign of progressive disease or relapse. The dose of thalidomide was reduced to 50% when grade II toxicity occurred, and suspended for any grade III. On December 2003, the protocol was amended and enoxaparin prophilaxys was added. The MP regimen was as MPT without thalidomide. The end points of the study were: response, EFS, OS and toxicity. The response rate among patients who received MPT was: 25.9% immunofixation negative CR (CR), 5.5% immunofixation positive near CR (nCR) 48.2% partial remission (PR) (M-protein reduction 50–99%), 9.3% stable disease (SD) (M-protein reduction 0–49%) and 11.1% progressive disease (PD). The response rate after MP was 4.2% CR, 0% nCR, 43.6% PR, 23% SD and 29.2% PD. Response was followed by significant improvement of performance status, skeletal pain, anemia and transfusion requirement. After a median follow up of 15 months, 38 patients relapsed: 11 (29%) after MPT and 27 (71%) after MP. The EFS @ 26 months was 67.8% for MPT and 32.4% for MP (P

Description: 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.

Description: Defibrotide (DF) showed antithrombotic properties and remarkable activity in Multiple Myeloma (MM), without significant anticoagulant effects and bleeding risk. DF may abrogate tumor cells interaction with marrow stromal cells and enhance sensitivity to chemotherapy, thus improving activities of Melphalan, Prednisone and Thalidomide, while protecting against thrombotic state. We designed a multicenter phase I/II trial to define efficacy and safety of Melphalan, Prednisone, Thalidomide and DF (MPTD) in relapsed/refractory MM. The MPTD treatment consisted of 6 35-days cycles of oral melphalan (0.25 mg/Kg day 1–4), prednisone (1.5 mg/kg day 1–4), thalidomide (50–100 mg/day continuously), DF at 3 dose levels (17 mg/Kg iv or 2.4 g po D 1–4, 1.6 g po D 5–35; 34 mg/Kg iv or 4.8 g po D 1–4, 3.2 g po D 5–35; 51 mg/Kg iv or 7.2 g po D 1–4, 4.8 g po D 5–35), every 35 days, without deep vein thrombosis (DVT) prophylaxis. Safety was assessed by defining dose-limiting toxicity (DLT) and maximum tolerated dose (MTD). DLT was defined as the occurrence of febrile neutropenia, G4 neutropenia 〉1 week, any other G4 hematologic toxicity, or any 〉G3 non-hematologic toxicity. MTD was the dose level prior to that resulting in DLT. Efficacy was evaluated according to EBMT/IBMTR criteria. Twenty-four patients were enrolled between March and November 2006 and 19 patients completed at least 1 MPTD (median age 69, excluding primary refractory and/or patients receiving anticoagulation) and were evaluated for toxicity and response. Fourty-two percent of patients achieved at least partial response (PR) after a median of 3 cycles (including 16% very good PR), without significant differences among DF dose. The MTD was not reached. DLTs observed were not considered related to DF and included: G3 ileus (1st dose level) and acute myocardial infarction (AMI) in the 2nd. Toxicities ≥G3 consisted of neutropenia 47%, thrombocytopenia 10%, anemia 21%, whereas

Description: Background: In newly diagnosed multiple myeloma (MM) patients the addition of lenalidomide or thalidomide or bortezomib to the standard oral melphalan and prednisone (MP) combination significantly increased response rate and event-free survival. In advanced MM, the 4 drug combination VMPT further improves response rate. In this multicenter open label phase I/II trial the safety/efficacy profile of the 4 drug combination, lenalidomide, melphalan, prednisone and thalidomide (RMPT) was evaluated in patients with relapsed/refractory myeloma. Methods: Oral lenalidomide was administered at 10 mg/day on days 1–21, oral melphalan at 0.18 mg/kg on days 1–4, oral prednisone at 2 mg/kg on days 1–4. Thalidomide was administered at 50 mg/day (Arm A) or 100 mg/day (Arm B) on days 1–28. Each course was repeated every 28 days for a total of 6 courses. Aspirin 100 mg/day was given as a prophylaxis for thrombosis. Maintenance therapy included lenalidomide alone at 10 mg/day on days 1–21. Results: Forthy-four patients, median age 69 years (range 47–80), with relapsed or refractory MM were enrolled. Twenty-six patients received RMPT as second line of therapy, 18 as third line. Twenty patients received prior autologous transplant, 10 thalidomide-based regimen, 9 bortezomib-based regimen and 3 allogeneic stem cell transplant. After a median of 2 courses, 75.8% of patients achieved at least a partial response (PR), including 30% very good partial response (VGPR). Among patients who received RMPT as second line therapy the PR rate was 81.8%, including VGPR 36.4%.Among patients who received thalidomide 100 mg, the PR rate was 93.3% (including VGPR 46.7%) compared to 64.7% of thalidomide 50 mg. The 1-year-progressionfree survival was 48.6% and the 1-year survival from study entry was 90%. Grade 3–4 hematologic adverse events included: neutropenia (66.6%), thrombocytopenia (36.3%) and anemia (30.2%). Grade 3–4 non hematologic adverse events included: infections (21.2%), neurological toxicity (6%) and fatigue (9%). No thromboembolic events were reported. Conclusion: Initial results showed that RMPT is an effective salvage therapy with a high proportion of responses. Toxicities were manageable. No thromboembolic complications were reported.

Description: Background: The association of Melphalan, Prednisone and Lenalidomide (MPR) has shown significant anti-myeloma activity in newly diagnosed Multiple Myeloma (MM) patients. In this phase I/II study, the more frequent adverse events were neutropenia and thrombocytopenia. Non-hematologic toxicities were unusual. Methods: We analyzed the kinetics and risk factors for neutropenia and thrombocytopenia in 21 patients (median age 69 years) who received nine four-week cycles of MPR at the maximum tolerated dose (melphalan 0.18 mg/Kg d 1–4, lenalidomide 10 mg d 1–21, prednisone 2 mg/Kg d 1–4, followed by maintenance period with lenalidomide 10 mg/day for 21 days every 4 weeks). We also up-dated efficacy end-point. At the occurrence of grade-3 neutropenia, G-CSF was administered for 5–7 days. The occurrence of grade-4 neutropenia despite G-CSF administration or any other grade-4 hematological toxicities required withholding of treatment and subsequent dose reduction at the start of the following cycle. A new cycle was allowed if the neutrophil count was 〉1×109/L and platelet count 〉50×109/L. A delay of 2 weeks was allowed, a delay beyond 2 weeks required dose reduction and a delay beyond 4 weeks required therapy discontinuation. Results: Grade-3 neutropenia occurred in 38.1% of patients, grade-4 neutropenia in 14.2% of patients, but febrile neutropenia was 9.5%. G-CSF was administered in 42.3% of patients. The mean neutrophil count at the start of each MPR cycle was 2.69 × 109/L (SD 1.4). The mean neutrophil count at nadir (day 15–21) of each cycle was 1.43 × 109/L (SD 1.0). The incidence and depth of neutropenia did not increase with the number of cycles. The mean neutrophil count during maintenance was 2.11 × 109/L (SD 1.0). Grade-3 thrombocytopenia occurred in 14.2% of patients and grade-4 thrombocytopenia in 9.5%; one patient required platelet transfusion. The mean platelet count at the start of each MPR cycle was 174 × 109/L (SD 63.9). The mean platelet count at nadir (day 15–21) of each cycle was 121 × 109/L (SD 56.3). Thrombocytopenia was more pronounced after 9 cycles of treatment. The mean platelet count after 9 cycles was 109 × 109/L (SD 53). The mean platelet count at the end of 6 months of lenalidomide maintenance therapy was 158 × 109/L (SD 79.2). One patient required lenalidomide dose reduction for severe neutropenia. Three patients discontinuated therapy for severe thrombocytopenia and neutropenia. Grade 3–4 hematologic toxicity was more frequent in patients with low baseline neutrophil count and in those with Bence-Jones myeloma. Neutropenic fever (9.5%), cutaneous reaction (9.5%), thromboembolism (4.8%) were the most frequent grade 3–4 non-hematologic adverse events. After a median follow-up of 29.5 months, the median time-to-progression was 28.5 months, the median progression-free survival was 28.5 months and the 2-years overall survival was 90.5%. No death was reported in the first 18 months of treatment. Conclusions: MPR is a promising first line regimen for elderly MM patients. Hematologic adverse events were frequent but manageable with the use of G-CSF.

Description: Bortezomib has been evaluated as induction regimen to improve cyto-reduction before autologous stem cell transplant. Combinations including bortezomib, doxorubicin and dexamethasone have shown encouraging results. Melphalan at 100 mg/m2 has been suggested as reduced-intensity conditioning regimen for elderly patients. In this prospective multicenter phase II study, bortezomib, pegylated-liposomal-doxorubicin and dexamethasone (PAD) followed by tandem melphalan 100 mg/m2 has been investigated in newly diagnosed patients aged 65–75 years. The induction regimen included four 21-day PAD cycles (bortezomib 1.3 mg/m2 days 1, 4, 8, 11, pegylated-liposomal-doxorubicin 30 mg/m2 day 4 and dexamethasone 40 mg days 1–4, 8–11, and 15–18 for cycle 1 and days 1–4 for cycles 2–4). Cyclophosphamide (3 g/m2) plus G-CSF were used to harvest stem cells. Patients were then conditioned with tandem melphalan 100 mg/m2 followed by stem cell infusion. A single interim analysis has been planned. Sixty-five patients have been enrolled in the study and 37 completed the induction cycles. Median age was 69 years; median β2-microglobulin 3 mg/L; median albumin 4.1 g/L; chromosome 13q deletion was detected by FISH in 35% of patients. After the 4 courses of PAD 97.1% of patients achieved at least a partial response (PR), 50% at least a very good partial response (VGPR), 11.8% an immunofixation negative complete remission (CR). After tandem melphalan 100 mg/m2, all patients achieved at least a PR, 80% at least a VGPR and 30% an immunofixation negative CR. After 4 cycles of PAD, grade 3–4 hematologic events were thrombocytopenia (13.5%) and neutropenia (8.1%); more frequent grade 3–4 non-hematologic toxicities were peripheral neuropathy (21.6%) and infections (10.8%). One early toxic death was reported (central nervous system bleeding) and two patients had to discontinue therapy due to pneumonia and HBV reactivation. Eighty-two percent of patients achieved successful stem cell harvest (〉4 CD34+ cells/Kg). PAD is an effective induction approach, it may improve autologous transplant results in selected elderly patients. Updated results of the interim analysis will be presented at the meeting.

Description: Background. Lenalidomide (Revlimid® ) is a novel, orally active immunomodulatory drug, effective in multiple myeloma (MM) patients. In newly diagnosed patients the addition of Thalidomide to the standard oral melphalan and prednisone (MP) significantly increase response rate and event free-survival compared with MP. No data are available on the clinical use of Revlimid® in combination with MP. In this multicenter phase I/II trial, we evaluate the dosing, safety and efficacy of the combination Revlimid® , melphalan and prednisone (R-MP). Methods. Patients (pts) with newly diagnosed symptomatic MM older than 65 years were treated with 9 courses of Revlimid® (5–10 mg/day for 21days every 4–6 weeks) plus MP (melphalan 0.18–0.25 mg/kg and prednisone 2 mg/kg for 4 days every 4–6 weeks) followed by maintenance therapy with Revlimid® alone (10 mg/day for 21days every 4–6 weeks). Four different dose-levels were tested: 1.melphalan 0.18 mg/kg + Revlimid® 5 mg/day; 2.melphalan 0.25 mg/kg + Revlimid® 5 mg/day; 3.melphalan 0.18 mg/kg + Revlimid® 10 mg/day; 4.melphalan 0.25 mg/kg + Revlimid® 10 mg/day. Each cohort included 6 pts, with additional 15 pts enrolled at dose level 3 and 4. All pts received ciprofloxacin and aspirin (100 mg/day) as prophylaxis. Results. Between January and October 2005, 54 pts (median age 71) were enrolled in the study. No DLTs were observed in the first 2 dose-levels. In dose-level 3, one pt experienced DLT (grade 4 neutropenia lasting〉7 days). In dose-level 4, three pts showed DLTs (neutropenic fever, grade 3 cutaneous toxicity, pulmonary embolism, delay in the start of cycle 2) during the first cycle. The MTD was defined at dose-level 3 (melphalan 0.18 mg/kg+Revlimid® 10 mg/day). In the dose-levels 3 and 4, after a median of 7 cycles, all patients showed at least a minimal response and 85.4% of patients showed at least a partial response (PR); 41.5% of patients achieved at least a very good partial response (VGPR) and 17.1% of patients reached immunofixation negative complete remission (CR). In the dose-level 3, defined as MTD, 85.6% of patients showed at least a PR, including 52.3% of patients who achieved at least a VGPR and 23.8% who showed immunofixation negative CR. After a median follow up of 9.6 months, the progression free survival (PFS) was 87% at 16 months. FISH informations on chromosome 13q deletion were available in 42 patients (79%): no difference in response rate and PFS was observed between patients with or without 13q deletion. Toxicity was manageable, and occurred more frequently during early cycles. Major grade 3–4 adverse events consisted of hematological toxicities (neutropenia 66%, thrombocytopenia 34% and anemia 17%); major grade 3–4 non-hematological toxicities were cutaneous eruption (10%) and febrile neutropenia (8%). Three cases of tromboembolic events occurred: two of them after aspirin discontinuation, at cycle 7 and during maintenance. Conclusions. R-MP induced a high proportion of responses and appeared to overcome the poor prognosis of patients with chromosome 13q deletion. It was well tolerated, toxicities were predictable and manageable. An update of these data will be presented.

Description: Abstract 1940 The combination of Melphalan-Prednisone-Lenalidomide (MPR) has shown promising results in elderly newly diagnosed myeloma patients. In the transplant setting, low-dose chemotherapy (induction) precedes high-dose chemotherapy (autologous transplantation consolidation). This approach reduces tumor mass, with few side effects, before achieving the maximum cyto-reduction with autologous transplantation. The same approach has been designed for the elderly patients. Accordingly induction with lenalidomide plus corticosteroids precedes consolidation with MPR. A two-stage phase II clinical trial was planned to evaluate the safety and efficacy of Lenalidomide-Prednisone (RP) as induction, followed by Melphalan-Prednisone-Lenalidomide (MPR) as consolidation and Lenalidomide as maintenance in elderly myeloma patients. Unfit patients with newly diagnosed symptomatic myeloma older than 65 years were enrolled. No exclusion criteria were included in the protocol, to avoid the selection of fit elderly subjects only. Patients with low blood count, abnormal performance status, hepatic, renal, cardiac or pulmonary functions were enrolled. Patients received 4 RP courses (Lenalidomide 25 mg/day for 21 days every 4 weeks, plus Prednisone 50 mg three times/week for 4 weeks) followed by 6 MPR cycles (Melphalan 2 mg and Prednisone 50 mg three times/week, for 4 weeks plus Lenalidomide 10–15 mg/day for 21 days every 4 weeks) and maintenance with Lenalidomide alone (10 mg/day for 21 days every 4 weeks). Two different dose-levels of Lenalidomide were tested in combination with MP: 15 mg (dose-level 1) and 10 mg (dose-level 2). Each cohort included 12 patients, with additional 22 patients enrolled at dose-level 2. Patients were evaluated for efficacy and toxicity after completion of at least 2 MPR cycles. Forty-six patients (median age 75, range 65–88) were enrolled. Thirty-six patients were evaluable after a median of 7 cycles and a median follow-up of 8.5 months. During RP induction, the most frequent grade 3–4 hematological adverse events were neutropenia (19%), anemia (11 %), thrombocytopenia (6%). During MPR consolidation, grade 3–4 adverse events were neutropenia (45%), and thrombocytopenia (3%). Neutropenia was increased by the addition of melphalan, but both thrombocytopenia and anemia were reduced. Non-hematological toxicities were more frequent during RP cycles and reduced during MPR cycles (cutaneous rash and infections). After RP induction, at least partial response (PR) rate was 67%, at least very good partial response (VGPR) was 17%. After 2 MPR cycles, PR rate increase to 72%, including 22% of patients who achieved at least a VGPR. Conclusions. Induction with RP followed by consolidation with MPR showed a manageable safety profile and reduced the risk of anemia, thrombocytopenia and non-hematological toxicity in unfit elderly myeloma patients. These data will be updated at the meeting. Disclosures: Palumbo: Celgene Srl: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janseen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees. Off Label Use: Lenalidomide in combination with melphalan for multiple myeloma patients at diagnosis. Guglielmelli:Celgene: Honoraria; Janseen-Cilag: Honoraria. Gay:Celgene: Honoraria. Cavallo:Celgene: Honoraria. Boccadoro:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janseen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.