ALBERT

Description: Abstract 2818 Poster Board II-794 INTRODUCTION: Bisphosphonate (BSFs) are an effective drug which have been mainly used in oncology for the treatment of solid tumour with bone metastasis, as well as for haematologic disease such as multiple myeloma (MM) and Waldenstrom's Macroglobulinemia (WM), but also prescribed in non neoplastic disease such osteoporosis and Paget's disease. As rare complications related to prolonged treatment with BSFs, an osteonecrosis of the jaw (BRONJ) in neoplastic and non neoplastic diseases is reported with an incidence between 2 and 15% as described in different casitics. The aim of this retrospective multicentric study is to describe the clinical aspects and the evolution of the osteo-necrotic lesions in a long term group of MM patients treated with BSFs. MATERIAL AND METHODS: We studied retrospectively 55 patients (pts) with MM or WM who developed BRONJ followed from January 2003 to January 2009 in different haematological departments. Median age was 72 years (range 56-95), male 16/ 39 female. Immunoglobulin isotype was: 25 pts IgG-κ; 6 pts IgG-α, 12 pts IgA-κ; 3 pts IgA-γ, 5 pts IgM-κ (WM), 3 pts MM light chain κ and 1 pt MM light chain γ. All patients have been treated with BSFs for bone lesions and/or factures: Pamidronate was used in 1 pt (1,8 %), Zolendronic acid in 36 pts (65,5 %), Pamidronate followed by zolendronate in 18 pts (32,7 %). The average dose of Pamidronate was 2.022 mg (range 90-6.750 mg) and of zoledronate was 84 mg (range 4-256 mg). Anatomic localisation of the BRONJ was: mandible 29 pts (52,7%); maxilla 22 pts (40%); mandible/maxilla 4 cases (7,3 %). The most common trigger for BRONJ was dentoalveolar surgery, including extractions (43 cases-78,4%), dental implant placement (3 patients-5,4%), periodontal disease (5 cases-9 %), and in 3 patients with dental prothesis (5,4%); only 1 patient (1,8%) developed BRONJ spontaneously. All patients stopped bsf therapy after BRONJ diagnosis. RESULTS: After a median observation of 26 months (range 1-110 months) no death for BRONJ complication was reported. All patients were treated with conservative treatment such as antibiotic therapy. In 18 patients (32,7%) antibiotic therapy was the only treatment used. Six patients (10,9%) received antibiotic associated with surgical debridement of necrotic bone. Sixteen patients (29%) were treated with antibiotic therapy in combination with ozonotherapy and curettage; twelve patients (21, 8%) required sequestrectomy in association with antibiotic and oxygen/hyperbaric therapy. Three patients (5, 4%) refused any therapy. Among the evaluable patients (53) complete response (CR) was observed in 20 cases (37.75%); partial response (PR) in 21 patients (39.6%) with improving as secondary infection and pain; the clinical finding was unchanged (SD) in 9 patients (16,3%) and 3 patients (5,4%) developed a worsening of the osteonecrosis (PD). CONCLUSIONS: In the unvariate analysis association of surgical treatment with antibiotic therapy, is more effective to eradicate the necrotic bone than antibiotic treatment alone (p=

Description: Background: Autologous stem cell transplantation (ASCT) improves outcome in comparison with chemotherapy (CC) innewly diagnosed multiple myeloma (NDMM) patients. The primary objective of our analysis was to compare progression-free survival (PFS) and overall survival (OS) of patients randomized to ASCT vs. chemotherapy (CC): we tested the hypothesis that benefit of ASCT could vary in different subsets of patients defined according to baseline prognostic features and response to induction. Methods: Data of 2 phase III multicenter randomized trials (RV-MM-PI-209 and RV-MM-EMN-441) enrolling patients younger than 65 years were pooled together. In both trials, patients received lenalidomide-dexamethasone induction and stem cell mobilization. Patients were randomized to either consolidation with 2 courses of Melphalan 200 mg/mq followed by ASCT (Mel200-ASCT) or 6 cycles of CC plus lenalidomide (CC+R) (RV-MM-PI-209: melphalan-prednisone-lenalidomide; RV-MM-EMN-441: cyclophosphamide-dexamethasone-lenalidomide). We evaluated PFS and OS of Mel200-ASCT vs. CC+R patients in the following subgroups, defined according to baseline features (Karnofsky performance status (PS) [60-70%, 80-100%], International Staging System (ISS) stage [I, II, III], cytogenetic profile [presence of del17 or t(4;14) or t(14;16); absence of del17, t(4;14) and t(14;16)]) and response to induction (≥very good partial response [VGPR],

Description: Introduction Elotuzumab (Elo), an immunostimulatory monoclonal antibody targeting signaling lymphocytic activation molecule F7 (SLAMF7), received marketing approval in Italy for relapsed or refractory multiple myeloma (RRMM), in combination with lenalidomide (R) and dexamethasone (d) (EloRd) in April 2017. Here we report preliminary data of an Italian real-life experience on EloRd as salvage therapy for RRMM patients treated outside of controlled clinical trials. The primary objectives of this study were to assess the toxicity profile and the efficacy of EloRd administered as salvage therapy in a real-world setting. Methods Retrospective data collection received approval from local ethic committee. The cohort included 180 RRMM patients from 28 Italian centers who received at least one cycle of EloRd as salvage treatment between April 2017 and June 2018. Patients were treated with EloRD according to marketing approval as follows: Elo 10 mg/kg i.v. on days 1, 8, 15, and 22 during the first two cycles and then on days 1 and 15 of each following cycle, R 25 mg on days 1 to 21 of each cycle and d at a dose of 40 mg during the week without Elo, and 36 mg on the day of Elo administration. Responsive patients had to reach at least a partial remission (PR). Results Baseline characteristics are shown in Table 1. Median age of the 180 patients was 72 years (range 48-89 years); 53.9% were males (Table 1). The median number of previous therapy regimens was 1 (range 1-7); 69 patients (38.3%) received a previous autologous stem cell transplantation (ASCT). One hundred and ten patients (61.1%) showed a symptomatic relapse, 36 (20%) a biochemical relapse, and 34 cases (18.9%) were refractory to the last therapy, including bortezomib in 12.8% of patients. Forty-four patients (24.4%) had creatinine clearance ≤60 mL/min. Among the 138 cases evaluable for International Scoring System (ISS), 54 (39.1%) had stage I, 56 (40.6%) stage II, and 28 (20.3%) stage III. At last data collection (June 2018), 164 cases were evaluable for response. The median number of courses administered so far was 5 (range 1-18). The overall response rate (ORR) was 78%, with 9 complete remissions (CRs) (5.5%) and 49 very good partial remissions (VGPRs) (35.4%). A significant higher ORR was observed in patients who had received only 1 previous line of therapy than those who had received 〉1 line (64% vs 37.5%; p=0.004). Age (

Description: Introduction Lenalidomide (Len) and low-dose Dexamethasone (dex) (Rd) in continuous is a new standard of care for elderly newly-diagnosed multiple myeloma (NDMM) patients (pts), as established by FIRST trial (Facon et al, Blood 2018). Methods and results This is a retrospective, multicentric study conducted in Italy with the aim of evaluating efficacy and tolerability of Rd in a real-life population. Thirty-seven centers were involved and data of 429 pts are available. Pts were considered eligible for the study when completing at least 2 cycles of Rd regimen. Table 1 summarizes the characteristics of pts at time of MM diagnosis. Median age was 78 years (range 57-92), 36.6% had an ECOG PS≥2, creatinine clearance (ClCr) was ULN (P=0.01) and ClCr2 still impact on OS (p

Description: Background The current treatment for newly diagnosed elderly multiple myeloma (MM) patients, not eligible for transplant, induces approximately 30% near-complete response/complete response (nCR/CR). Carfilzomib is a novel, irreversible proteasome-inhibitor with significant activity and favourable toxicity profile, including very low rates of peripheral neuropathy and neutropenia. We evaluated efficacy and safety of the combination carfilzomib-cyclophosphamide-dexamethasone (CCd) in elderly newly diagnosed MM patients. Methods The Bryant and Day two-stage design was used to evaluate both efficacy and safety. Patients received oral cyclophosphamide (300 mg/m2 on days 1,8,15), oral dexamethasone (40 mg on days 1, 8, 15, 22) and iv carfilzomib administered over 30 minutes (20 mg/m2 on days 1, 2, and 36 mg/m2 on days 8, 9, 15, 16, cycle 1; 36 mg/m2 on days 1, 2, 8, 9, 15, 16, cycles 2-9) every 28 days for 9 cycles, followed by maintenance with iv carfilzomib (36 mg/m2 on days 1, 2, 15, 16) every 28 days until progression or intolerance. Results Enrollment is complete (58 pts): median age was 71 years, 28% of patients were older than 75 years, 40% had ISS stage III, 35% had unfavorable FISH profile [t(4;14) or t (14;16) or del17p] and 31% are frail, defined according to Charlson co-morbidity index (≥2), geriatric assessment score ADL (

Description: Background: The role of Minimal residual disease (MRD) as surrogate for survival in Multiple Myeloma (MM) patients is well established. Therefore, new response criteria recommend including Multiparameter Flow cytometry (MFC) and next generation Sequencing (NGS) MRD negativity (minimum sensitivity of 1 in 105 nucleated cell) to deeply characterize complete remission (CR) [Kumar SK, Lancet Oncol 2016]. Here we analyzed and compared MRD data from the FORTE trial both by MFC and NGS techniques. Methods: Newly diagnosed MM patients ≤65 years were randomized to receive carfilzomib, lenalidomide, dexamethasone (KRd) induction - autologous stem cell transplantation (ASCT) intensification - KRd consolidation (KRd_ASCT); KRd12 and carfilzomib, cyclophosphamide, dexamethasone (KCd) induction - ASCT intensification - KCd consolidation (KCd_ASCT). Thereafter, patients were randomized to maintenance therapy with lenalidomide alone or lenalidomide plus carfilzomib. MRD evaluation was performed by 8-color second generation flow cytometry (sensitivity 10-5) in patients who achieved at least a very good partial response (VGPR) before maintenance. In a subgroup of these ≥ VGPR patients, next generation flow (NGF; sensitivity 10-5 - 10-6) was performed. Moreover, in patients achieving ≥ CR, MRD pre-maintenance was also assessed by NGS (Adaptive Biotechnologies, Seattle, WA; sensitivity 10-5 - 10-6). Therefore, only patients achieving ≥ CR have both MFC and NGS evaluations, and we focused on this ≥ CR population to compare MRD results with the 2 techniques. Spearman's rank correlation coefficient was used to measure the concordance between MFC and NGS. Fisher or Pearson's Chi-squared tests were adopted, where appropriate, to evaluate the statistical significance, at the level of 0.05. Results: ≥ CR pre-maintenance was achieved in 233 patients enrolled in the trial; at data cut-off, MFC and NGS data were available for 176/233 (76%) patients who were included in this analysis (62 received KRd_ASCT, 65 KRd12 and 49 KCd_ASCT). Median age of this ≥ CR population is 57 years (IQR 52-62), 14% have International Staging System (ISS) III stage and 26% high risk cytogenetics by FISH features [either del(17p) or t(4;14) or t(14;16)] reflecting baseline clinical features of the entire FORTE population. 139/176 (79%) ≥ CR patients were MFC negative at a cut-off of at least 10-5. Rate of MRD negative MFC among ≥ CR negative in the 3 arms were: 53/62 (85%) in KRd_ASCT, 51/65 (78%) in KRd12 and 35/49 (71%) in KCd_ASCT, reflecting the higher rate of MCF MRD negativity pre-maintenance reported by ITT in the overall population in the 2 KRD arms [Gay F, ASH 2018]. NGS negativity at a cut-off of at least 10-5 was detected in 87/176 (49%) of ≥ CR patients. Rate of MRD negative NGS at least 10-5 among ≥ CR negative in the 3 arms were: 35/62 (56%) in KRd_ASCT, 31/65 (48%) in KRd12 and 21/49 (43%) in KCd_ASCT. NGS negativity at a cut-off 10-6 was detected in 34/123 (28%) of ≥ CR patients (for 53/176 CR patients 10-6 sensitivity was not reached). Rate of MRD negative NGS at least 10-6 among ≥ CR negative in the 3 arms were:14/41 (34%) in KRd_ASCT, 10/44 (23%) in KRd12 and 10/38 (26%) in KCd_ASCT. Thereafter, we have analyzed the concordance between MRD results by the two techniques. Overall (samples at 10-5 and 10-6 sensitivity), Spearman's coefficient is 0.63 (p 〈 0.001); discordances between the two methods have been observed in 54/176 paired samples (30%). In particular, 53 samples (30%) are NGS positive but MFC negative, of which 34/53 (64%) have reached 10-6 sensitivity by NGS. Only 1 MFC positive sample is NGS negative. In a subgroup of patients evaluable both by NGS and NGF (26 paired samples, sensitivity 10-6), Spearman' s coefficient is 0.83 (p 〈 0.001), although a higher sample size is needed to confirm these preliminary concordant results. Conclusion: In patients who achieved ≥ CR, rate of at least 10-5 MRD MCF negativity was 79% and rate of at least 10-5 NGS negativity was 49%. Assessment both by MFC and NGS showed a good concordance, particularly if the same sensitivity is reached. Longer follow up is needed to assess the impact of MFC in comparison with NGS on patients' outcomes, particularly to evaluate if 10-6 NGS or NGF sensitivity may provide further clinical information, possibly identifying patients with very long survival or potentially cured. Disclosures Oliva: Celgene: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Belotti:Janssen: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Galli:Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Leadiant (Sigma-Tau): Honoraria; Janssen: Honoraria; Celgene: Honoraria. Offidani:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Vozella:Amgen: Honoraria; Celgene: Honoraria. Zambello:Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Kirsch:Adaptive Biotechnologies: Employment. Jacob:Adaptive Biotechnologies: Employment, Other: shareholder. Ballanti:Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Corradini:Roche: Honoraria; Sanofi: Honoraria; KiowaKirin: Honoraria; Kite: Honoraria; Novartis: Honoraria, Other: Travel Costs; BMS: Other: Travel Costs; Servier: Honoraria; Takeda: Honoraria, Other: Travel Costs; Gilead: Honoraria, Other: Travel Costs; AbbVie: Consultancy, Honoraria, Other: Travel Costs; Amgen: Honoraria; Celgene: Honoraria, Other: Travel Costs; Daiichi Sankyo: Honoraria; Jazz Pharmaceutics: Honoraria; Janssen: Honoraria, Other: Travel Costs. Omedé:Janssen: Membership on an entity's Board of Directors or advisory committees. Cavo:takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; bms: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; novartis: Honoraria; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Musto:Amgen: Honoraria; Celgene: Honoraria. Boccadoro:Sanofi: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; AbbVie: Honoraria; Mundipharma: Research Funding. Gay:AbbVie: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: The presentation includes discussion of off-label use of a drug or drugs for the treatment of multiple myeloma.

Description: Complete response (CR) was an uncommon event in elderly myeloma patients until novel agents were combined with standard oral melphalan-prednisone. This analysis assesses the impact of treatment response on progression-free survival (PFS) and overall survival (OS). We retrospectively analyzed 1175 newly diagnosed myeloma patients, enrolled in 3 multicenter trials, treated with melphalan-prednisone alone (n = 332), melphalan-prednisone-thalidomide (n = 332), melphalan-prednisone-bortezomib (n = 257), or melphalan-prednisone-bortezomib-thalidomide (n = 254). After a median follow-up of 29 months, the 3-year PFS and OS were 67% and 27% (hazard ratio = 0.16; P 〈 .001), and 91% and 70% (hazard ratio = 0.15; P 〈 .001) in patients who obtained CR and in those who achieved very good partial response, respectively. Similar results were observed in patients older than 75 years. Multivariate analysis confirmed that the achievement of CR was an independent predictor of longer PFS and OS, regardless of age, International Staging System stage, and treatment. These findings highlight a significant association between the achievement of CR and long-term outcome, and support the use of novel agents to achieve maximal response in elderly patients, including those more than 75 years. This trial was registered at www.clinicaltrials.gov as #NCT00232934, #ISRCTN 90692740, and #NCT01063179.

Description: Abstract 3419 Poster Board III-307 Background Bortezomib induction before autologous stem cell transplantation (ASCT) has shown its efficacy in newly diagnosed multiple myeloma (MM) patients, both in association with dexamethasone alone (Harousseau JL, et al. Blood 110, 2007, abstr 450) and in combination with doxorubicin and dexamethasone (Popat R, et al. Br J Haematol 141:512-516, 2008). Lenalidomide, a less toxic and more potent thalidomide-derivative, lacks the neurotoxic effects of the parent drug and represents an optimal agent to include in maintenance regimens. Aims These observations provided the rationale for investigating a sequential approach including bortezomib as induction and lenalidomide as consolidation-maintenance in MM patients undergoing ASCT. Methods A hundred and two newly diagnosed patients aged 65–75 years were enrolled in 17 Italian centers. Induction (PAD) included four 21-day cycles of bortezomib (1.3 mg/m2 days 1,4,8,11), pegylated-liposomal-doxorubicin (30 mg/m2 day 4), and dexamethasone (40 mg/day: cycle 1, days 1–4, 8–11, 15–18; cycles 2–4, days 1–4). Autologous transplantation was tandem melphalan 100 mg/m2 (MEL100) followed by stem-cell support. After ASCT, patients received consolidation with four 28-day cycles of lenalidomide (25 mg/day days 1–21 every 28 days) plus prednisone (50 mg every other day) (LP), followed by maintenance (L) with lenalidomide alone (10 mg/day days 1–21 every 28 days) until relapse. Primary endpoints were safety (incidence of grade 3–4 adverse events [AEs]) and efficacy (response rate). Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Time-to-event estimates analysis was performed using the Kaplan-Meier method. Results Very good partial response (VGPR) or better was 58% after PAD induction and increased to 82% after MEL100 and to 86% during LP-L. Complete response (CR) rate was 13% after PAD induction, increased to 38% after MEL100 and to 66% during LP-L. After a median follow-up of 2 years, the 2-year PFS was 69%, the 2-year time-to-progression was 75% and the 2-year OS was 86%. During PAD induction, main grade 3–4 AEs were thrombocytopenia (17%), neutropenia (10%), peripheral neuropathy (16%), and pneumonia (10%); treatment-related mortality was 3%. During consolidation-maintenance grade 3–4 AEs included neutropenia (16%), thrombocytopenia (6%), pneumonia (5%), and cutaneous rash (4%). Consolidation-maintenance treatment was well tolerated: only 4% of patients required Granulocyte-colony stimulating factor support and no patient required platelet transfusion; dermatological toxicity was easily manageable with dose-reduction and supportive therapy; no treatment-related deaths were reported. Updated results will be presented at the meeting. Conclusion This is the first phase II study in newly diagnosed MM patients to date, where a sequential approach including bortezomib as induction, and lenalidomide as post ASCT consolidation-maintenance was explored. Treatment was correlated with an increase in response rate and in the depth of response (CR rate) and was generally well tolerated. These data suggest that this is a safe and effective regimen for newly diagnosed MM patients. Randomized trials are needed to confirm these results. Disclosures Patriarca: Celgene: Honoraria; Janssen Cilag: Honoraria. Bringhen:Celgene: Honoraria; Janssen Cilag: Honoraria. Boccadoro:Janssen Cilag : Consultant, advisory committee, Research Funding; Celgene: Consultant, advisory committee, Research Funding; Pharmion: Consultant, advisory committee, Research Funding. Palumbo:Celgene: Honoraria; Janssen Cilag: Honoraria.

Description: INTRODUCTION: Bortezomib (B) is the first proteasome inhibitor to be used in clinical practice and has been recently approved for second line treatment of multiple myeloma (MM) patients(pts). Several trials demonstrated that Bortezomib is relatively well tolerated; however, manageable non-hematologic and hematologic toxicity has been reported. The dose limiting toxicity is peripheral neuropathy (PN), reported up to 35% of the patient population. AIM: We evaluated the incidence and severity of PN in 179 MM patients that received B as single agent or in combination. MATERIAL AND METHODS: Patients characteristics were as follows: median age was 66.7 years (range: 32–82) with 52% male; 55 patients were at the onset of the disease, 124 were pre-treated. Median time from diagnosis to treatment with B was 25.4 months (range 0–111), median value of β2-microglobulin was 3.02 (0.2–20). Risk factors for PN included prior use of thalidomide in 68 patients (38%), vincristine in 75 patients (41.8%) and 15 patients (8.8%) had diabetes mellitus. RESULTS: Patients received bortezomib alone (?) or in combination with either dexamethasone (n=52), or chemotherapy (n=114) or thalidomide (n=38). Overall, the response rate (≥PR) was 86%. PN of grade ≥2 was observed in 73 pts (41%); grade 3–4 occurred in 32 (18%). Median time to the onset of bortezomib-related PN was 84 days (range, 10–449) after bortezomib initiation. In most cases (93%), patients had sensory symptoms, while 5 patients (7%) experienced both sensory and motor symptoms. Bortezomib-related PN led to therapy discontinuation in 31 pts (17%). For PN treatment, pts received mostly supportive therapy (analgesics, gabapentin, pregabalin, amitriptyline and vitamin supplements). Of the 31 patients with bortezomib-related PN that required discontinuation, resolution or improvement occurred in 16 (51.6%), at a median time of 140 days (range, 27–346) from B discontinuation. Data analysis of the PN risk factors (age, diabetes, sex, β2M, neurotoxic pre-treatment) showed a significant association with age 〉75 years (p

Description: Abstract 3069FN2 Background: High-dose chemotherapy with haemopoietic stem-cell improves outcome in multiple myeloma (MM). The introduction of novel agents questions the role of autologous stem-cell transplantation (ASCT) in MM patients. Aims: In this prospective randomized study, we compared conventional melphalan-prednisone-lenalidomide (MPR) with tandem high-dose melphalan (MEL200) in newly diagnosed MM patients younger than 65 years. Methods: All patients (N=402) received four 28-day cycles of lenalidomide (25 mg, d1-21) and low-dose dexamethasone (40 mg, d1, 8, 15, 22) (Rd) as induction. As consolidation, patients were randomized to MPR (N=202) consisting of six 28-day cycles of melphalan (0.18 mg/kg d1-4), prednisone (2 mg/kg d1-4) and lenalidomide (10 mg d1-21); or tandem melphalan 200 mg/m2 MEL200 (N=200) with stem-cell support. All patients enrolled were stratified according to International Staging System (stages 1 and 2 vs. stage 3) and age (