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High-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) remains the standard of care for patients younger than 65 years of age with multiple myeloma (MM). However, this therapeutic approach has undergone substantial advances in this last decade, mainly due to the introduction of new drugs such as thalidomide, lenalidomide and bortezomib. These new drugs, in different combinations, have shown to significantly increase response rates after induction therapy and ASCT. Moreover, the positive results obtained with these agents in consolidation and maintenance strategies after ASCT strongly support the concept of continuous therapy, whose ultimate goal is the long-term control of the disease and the improvement of outcome. Preliminary data from studies investigating next generation proteasome inhibitors, such as carfilzomib and ixazomib, used upfront as well as at subsequent therapeutic lines, demonstrate the possibility of achieving molecular remission in most of the patients. The deeper responses obtained with new drugcombinations questioned the role of ASCT, and large, ongoing, phase 3 trials will shed light on the role and the timing of ASCT.

Bringhen: Mundipharma: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Celgene: Honoraria; Bristol Myers Squibb: Honoraria; Karyipharm: Membership on an entity's Board of Directors or advisory committees. Offidani: 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. Musto: Celgene: Honoraria; Janssen: Honoraria. Gaidano: Gilead: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Roche: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. De Sabbata: Celgene: Membership on an entity's Board of Directors or advisory committees. Palumbo: Sanofi: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Binding Site: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Merck: Consultancy, Honoraria, Research Funding; Genmab A/S: Consultancy, Honoraria, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Employment, Equity Ownership, Honoraria, Research Funding. Hájek: Amgen, Takeda, BMS, Celgene, Novartis, Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Honoraria; Pharma MAR: Consultancy, Honoraria. Boccadoro: Novartis: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; AbbVie: Honoraria; Mundipharma: Research Funding; Sanofi: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding.

Introduction: Rd and MPR showed to be effective combinations in elderly newly diagnosed multiple myeloma (NDMM) patients (pts). Cyclophosphamide is a less toxic alkylating alternative agent. EMN01 is the first trial to formally compare these three different Lenalidomide-based combinations. Maintenance with Lenalidomide has been recently approved in patients eligible for autologous stem cell transplant (ASCT). Few data are available about the best combination as maintenance in patients not eligible for ASCT.

Offidani: Celgene: Honoraria, Research Funding; Janssen: Honoraria.

Introduction:Multiple Myeloma (MM) is a heterogeneous disease with a very wide range of progression free survival (PFS) and overall survival (OS) duration. At now, Revised- International Staging System (R-ISS), that classifies patients as low- (LR), intermediate- (IR) and high-risk (HR) according to ISS, cytogenetic and lactate dehydrogenase (LDH), is the most powerful tool to stratify patients with different outcome. Nevertheless, there is still too much variability in outcome in each risk group, particularly in the IR risk group, that deserves further dissection. However, this variability, behind initial prognostic factors, may be still dependent on dynamic features that are unpredictable at diagnosis and that could provide information during the course of the disease.

Offidani: Celgene, Janssen: Honoraria. Off Label Use: Lenalidomide. Corvatta:Celgene, Janssen: Honoraria. Bringhen:Onyx: Consultancy; Janssen-Cilag, Celgene, Novartis: Honoraria; Merck Sharp & Dohme: Membership on an entity's Board of Directors or advisory committees. Gentili:Celgene, Janssen: Honoraria. Gay:Celgene, Janssen: Honoraria. Boccadoro:Celgene, Janssen: Consultancy, Honoraria. Palumbo:Celgene, Janssen: Consultancy, Honoraria, Research Funding.

Introduction.Multiple myeloma (MM) represents a population with an increased risk of developing infection up to 10-fold if compared with controls. Moreover, patients treated with new-drugs are at higher risk of infections compared with those treated previously (Blimark C. et al. Haematologica 2015). Grade 3-4 non-hematological toxicity, particularly cardiac and infection complications, are associated with shorter OS in patients with MM (Bringhen S. et al. Haematologica 2013) whereas thrombosis did not. Anyway, guidelines to prevent thrombosis are available but there are not as regard infections although they would be advisable since infections still represent one of leading non-hematological adverse event in any protocols.

Larocca: Janssen Cilag: Honoraria; Celgene: Honoraria. Off Label Use: Use off-label of lenalidomide (immunomodulatory drug), carfilzomib (proteasome inhibitor), subcutaneous bortezomib (proteasome inhibitor) in terms of schedule used and combination.. Bringhen:Onyx: Consultancy; Merck Sharp & Dohme: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Janssen and Cilag: Honoraria; Celgene: Honoraria. Hajek:Janssen: Honoraria; Celgene: Consultancy, Honoraria; Merck: Consultancy, Honoraria. Offidani:Celgene: Honoraria; Janssen: Honoraria. Maracci:Mundipharma: Honoraria. Gay:Sanofi: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Marasca:Janssen: Honoraria; Celgene: Honoraria. Giuliani:Celgene: Research Funding. Musto:Janssen: Honoraria; Celgene: Honoraria. Boccadoro:Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Onyx: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees. Sonneveld:Millenium: Honoraria, Research Funding; Onyx: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Palumbo:Celgene: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Millennium Pharmaceuticals, Inc.: Consultancy, Honoraria; Onyx Pharmaceuticals: Consultancy, Honoraria; Array BioPharma: Honoraria; Amgen: Consultancy, Honoraria; Sanofi: Honoraria; Genmab A/S: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria.

Offidani: Mundipharma, Janssen: Honoraria. Off Label Use: Bendamustine. Corvatta:Janssen: Honoraria. Ballanti:Janssen: Honoraria. Brunori:Janssen: Honoraria.

Introduction:Bendamustine, a bifunctional alkylating agent, exerts a mechanism of action different from that of other conventional alkylators despite it remains mostly unknown. In patients with newly diagnosed or relapsed-refractory MM bendamustine has proven to be active either as monotherapy or in combination with new drugs, particularly bortezomib and immunomodulatory agents.

Offidani: Mundipharma: Honoraria, Research Funding. Off Label Use: Bendamustine.

Bendamustine, a bi-functional alkylating agent comprising a purine-like benzimidazole ring an a nitrogen mustard group, exerts a peculiar mechanism of action if compared to most conventional alkylators and this may partially explain its effectiveness in alkylator-resistant cells. In patients with MM several studies demonstrated the efficacy and tolerability of bendamustine as monotherapy or in combination with new drugs, particularly bortezomib that was found to enhance the in vitro sensitivity of MM cells to bendamustine.