Abstract: In polycythemia vera (PV), the prognostic relevance of an ELN-defined complete response (CR) to hydroxyurea (HU), the predictors of response, and patients’ triggers for switching to ruxolitinib are uncertain. In a real-world analysis, we evaluated the predictors of response, their impact on the clinical outcomes of CR to HU, and the correlations between partial or no response (PR/NR) and a patient switching to ruxolitinib. Among 563 PV patients receiving HU for ≥12 months, 166 (29.5%) achieved CR, 264 achieved PR, and 133 achieved NR. In a multivariate analysis, the absence of splenomegaly (p = 0.03), pruritus (p = 0.002), and a median HU dose of ≥1 g/day (p 〈 0.001) remained associated with CR. Adverse events were more frequent with a median HU dose of ≥1 g/day. Overall, 283 PR/NR patients (71.3%) continued HU, and 114 switched to ruxolitinib. In the 449 patients receiving only HU, rates of thrombosis, hemorrhages, progression, and overall survival were comparable among the CR, PR, and NR groups. Many PV patients received underdosed HU, leading to lower CR and toxicity rates. In addition, many patients continued HU despite a PR/NR; however, splenomegaly and other symptoms were the main drivers of an early switch. Better HU management, standardization of the criteria for and timing of responses to HU, and adequate intervention in poor responders should be advised.

Abstract: Background: The presence of peripheral blasts (PB) is a negative prognostic factor in patients (pts) with primary and secondary myelofibrosis (PMF/SMF) and PB ≥4% was associated with a particularly unfavorable prognosis (Masarova L et al, Cancer 2020). Ruxolitinib (RUX) is the JAK1/2 inhibitor most used for treatment of MF-related splenomegaly and symptoms. Its role has not been assessed in correlation with PB. Aims: To evaluate the impact of PB percentage on RUX efficacy and prognosis Methods: After IRB approval, the "RUX-MF" retrospective study collected 804 RUX-treated chronic-phase (CP, defined as PB & lt;10%) pts in 26 Hematology Centers. In 794 pts, PB count was evaluated by morphology at RUX start and correlated with treatment success and outcome. Risk category was assessed according to DIPSS (Passamonti F et al, Blood. 2010). Spleen (SR) and symptoms (SyR) response were assessed using IWG-MRT criteria (Tefferi A et al, Blood. 2013). Comparisons of quantitative variables between the 3 groups were carried out by Kruskal-Wallis and Dunn's tests while association between categorical variables was tested by the χ2 test. Variables significantly associated to RUX stop/leukemic transformation (LT)/overall survival (OS) in univariate analysis (Log-rank test) were considered for multivariable analyses, carried out using the Cox regression model, with evaluation of the model's performance in terms of goodness of fit. Results: Pts were categorized according to PB at RUX start: PB-0 (no PB; n. 487, 61.3%), PB-5 (PB 1-5%; n. 283, 35.8%), and PB-9 (PB 6-9%; n. 24, 2.9%). Pts characteristics at RUX start were: median age 68.1y (24-89); males 58.1%; PMF 52.5%; JAK2, CALR and MPL mutated: 80.5%, 13.1% and 2% (4.4% triple negative), high DIPSS: 7.6%; PLT & lt;100/WBC & gt;25 x10 9/l: 10.8%/16.4%; spleen length ≥10 cm: 47.8%, TSS ≥20: 60.6%; ≥1/≥2 high-risk mutation (HMR): 69/18 out of 167 evaluable (41.3%/10.8%); fibrosis grade ≥2: 77.9%; starting/cumulative RUX dose ≥15 mg BID: 61.4%/52.6%. Higher PB count was associated to high DIPSS risk (PB-0: 1.9%, PB-5: 16.2%, PB-9: 21.7%, p & lt;0.001), PLT & lt;100 x10 9/l (PB-0: 17.6%, PB-5: 15.1%, PB-9: 26.1%, p & lt;0.001), fibrosis grade ≥2 (PB-0: 73.3%, PB-5: 84.2%, PB-9: 100%, p & lt;0.001), spleen length ≥10 cm (PB-0: 43%, PB-5: 55.1%, PB-9: 59.1%, p=0.003). At 3 and 6 mos, 26.9% and 30.4% of evaluable pts achieved a SR, while 59.7% and 68.1% were in SyR, respectively. At 3 mos, SR (PB-0: 31.8%, PB-5: 20.6%, PB-9: 10%, p=0.001) and SyR (PB-0: 62.9%, PB-5: 55.5%, PB-9: 36.8%, p=0.02) were less frequently achieved by PB-5 and PB-9 pts compared to PB-0 pts. This association remained significant for SR at 6 mos (PB-0: 35%, PB-5: 23.9%, PB-9: 14.3%, p=0.006) and for both SR (p=0.003) and SyR (p=0.01) at any time. After a median RUX exposure of 1.5 y (0.1-8.9), 491 (61.8%) pts stopped RUX, 110 (13.9%) had a LT and 365 (46%) died. In univariate analysis, at 2y PB-9 pts had higher rates of RUX stop (73.9% vs 40.8% and 34.3% in PB-5 and PB-0 pts, log-rank p & lt;0.001) and LT (38.5% vs 10.2% and 6.2% in PB-5 and PB-0 pts, log-rank p=0.003). Median survival times of PB-0, PB-5 and PB-9 patients were 5.8, 4.9 and 2 years, respectively (log-rank p & lt;0.001) (Figure 1). In multivariable analysis, PB-9 pts confirmed their association with: 1) RUX stop (HR 3.74, 95%CI 1.51-3.70, p & lt;0.001), with TSS & gt;20 (HR 1.66, 95%CI 1.05-2.61, p=0.03), and HMR≥2 (HR 2.69, 95%CI 1.26-4.47, p=0.007); 2) LT (HR 3.71, 95%CI 1.71-8.04, p & lt;0.001), with HMR≥2 (HR 7.10, 95%CI 2.28-22.1, p & lt;0.001); 3) OS (HR 2.40, 95%CI 1.60-3.60, p & lt;0.001), with age≥65 (HR 2.31, 95%CI 1.17-4.57, p=0.02) and HMR≥2 (HR 3.21, 95%CI 1.67-6.20, p & lt;0.001). Unfavorable association with LT and OS was confirmed also in patients with HMR≥1. Conclusions: CP-MF pts with PB & gt;5% have a worse response to RUX and a worse outcome. Personalized approaches beyond RUX monotherapy may be useful in this context. Further clinical trials evaluating combination strategies and new drugs are required. Figure 1 Figure 1. Disclosures Palandri: Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; AOP: Membership on an entity's Board of Directors or advisory committees; Sierra Oncology: Membership on an entity's Board of Directors or advisory committees; CTI: Consultancy. Abruzzese: Bristol Myers Squibb: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Iurlo: Bristol Myers Squibb: Speakers Bureau; Pfizer: Speakers Bureau; Novartis: Speakers Bureau; Incyte: Speakers Bureau. Bonifacio: Bristol Myers Squibb: Honoraria; Novartis: Honoraria; Pfizer: Honoraria; Amgen: Honoraria. Cuneo: AbbVie: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau. Pane: AbbVie; Amgen; Novartis: Other: Travel, accommodation, expenses; Novartis Pharma SAS;: Research Funding; AbbVie; Amgen; Novartis, GSK , Incyte: Consultancy; AbbVie; Amgen; Novartis, GSK, Incyte: Speakers Bureau. Lemoli: Celgene: Other: Support for attending meetings and/or travel; Jazz, Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie, Daiichi Sankyo, Servier: Honoraria, Speakers Bureau. Cavo: Bristol-Myers Squib: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Speakers Bureau; Adaptive Biotechnologies: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Accommodations, Speakers Bureau; GlaxoSmithKline: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Breccia: Novartis: Honoraria; Pfizer: Honoraria; Incyte: Honoraria; Bristol Myers Squibb/Celgene: Honoraria; Abbvie: Honoraria.

Abstract: Introduction: Polycythemia Vera (PV) is a myeloproliferative neoplasm characterized by excessive red cell production and release of pro-inflammatory cytokines resulting in increased thrombotic risk, presence of systemic symptoms and reduced overall survival (OS). Abnormal body mass index (BMI) and comorbidities, as categorized by the Charlson Comorbidity Index (CCI), were found to influence treatment success and survival in several hematological malignancies, including myelofibrosis (MF). We evaluated the impact of CCI and BMI on the outcome of PV pts on the basis of real-world data. Methods: A network called "PV-NET" started in January 2019 including clinical/laboratory data of 2016 WHO-defined PV pts diagnosed and followed in 16 European Hematology Centers. Data cut-off was June 2019. OS was calculated from PV diagnosis to last contact or death (log-rank p). Cumulative incidences of events (thromboses, hemorrhages, infections, second neoplasia, and evolution into blast phase [BP] or MF) were conducted with Fine & Gray model with death as competing risk. Therapies were treated as time-to-event variables. Results: A total of 530 PV pts were collected. Median follow-up was 5.4 yrs (0.5-34) (total observation: 3633 pt-yrs). Main characteristics at diagnosis were: median age: 62.4 yrs (18.3-89.5); males: 53.4%; median (range) leukocyte/platelet count, x109/l: 9.8 (1.1-33)/448 (143-1386); median hemoglobin (g/dl)/hematocrit (%): 18.6/56 (males); 17.6/54.4 (females). Sixty-four (12.1%) and 34 (6.4%) pts had a thrombosis prior to or at diagnosis, respectively. At least one cardiovascular risk factor (CVRF) among smoke, diabetes, and hypertension was present in 343 pts (64.7%). Age-adjusted CCI was 0 (15.9%), 1 (18.9%), 2 (23.8%), and ≥3 (41.5%). Median BMI was 24 (17.4-37.3); 3.3%, 51.2%, 35.9% and 9.6% were underweight (BMI 〈 18.5), normal weight (18.5-24.9), overweight (BMI≥25) or obese (BMI≥30), respectively. Baseline features were comparable across BMI and CCI categories, but male pts were significantly more likely to have a BMI≥25 than female (p 〈 0.001). During follow-up, 64 all-grades thromboses (arterial, 56.3%), 29 bleedings, 56 infections and 66 second neoplasia were recorded. Overall, 13 pts progressed to BP and 32 to MF. Thirty-three pts died, because of BP (27.3%), second neoplasia (24.2%), MF (15.2%), old age (9.1%), thrombosis (6.1%) or other causes (18.1%). Incidence rates per 100 pt-yrs of all-grades events were: 1.5 (thromboses), 0.7 (bleedings), 1.4 (infections), 1.6 (second neoplasia), 0.4 (BP) and 0.9 (MF). Pts with CCI≥2 had a significantly higher rate of second neoplasia (p=0.01) and infections (p=0.03) over time and a worse OS (p 〈 0.001) compared to pts with CCI 〈 2. A BMI 〈 25 was associated with a higher probability of MF progression (p=0.02) and with reduced OS (p=0.04) (Fig.1). Notably, thrombotic risk was not influenced by CCI (p=0.16) and BMI (p=0.43). Pts received phlebotomies (PHL) (92.1%), hydroxyurea (HU) (82.6%), interferon (IFN) (7.9%), busulfan (2.6%), and ruxolitinib (RUX) (10.9%). Pts with CCI≥2 were significantly less treated with IFN (p 〈 0.001) and received more frequently HU (p 〈 0.001); notably, CCI did not influence the decision to start RUX (p=0.41). All pts treated with IFN but two had a BMI 〉 18.5; both underweight pts discontinued IFN due to intolerance. Overall, 0.8%, 19.4%, and 38.1% of pts had grade≥2 toxicity and/or stopped therapy because of intolerance during PHL, HU, and IFN, respectively. IFN intolerance tended to be more frequent in pts with CCI≥2 (p=0.06). Conclusions: CCI and BMI are rarely assessed in PV but may influence treatment strategy and survival. Particularly, CCI/BMI oriented the choice of IFN, but not RUX. Overweight PV pts had an improved survival, mimicking the "obesity paradox" observed in non-malignant CV diseases (Elagizi, et al. 2018). However, BMI may not be a reliable measure of adiposity. In cancer pts, an under/normal-weight may mask a hypercatabolic state with lean mass loss caused by a more aggressive disease, as supported by a higher rate of MF evolutions in pts with BMI 〈 25. Quantified body composition and careful control of comorbid conditions can improve PV management, prognostication and outcome. Disclosures Benevolo: Novartis Pharmaceuticals: Consultancy. Elli:Novartis: Membership on an entity's Board of Directors or advisory committees. Latagliata:Novartis: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Pfizer: Honoraria. Tiribelli:Pfizer: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Heidel:Celgene: Consultancy; CTI: Consultancy; Novartis: Consultancy, Research Funding. Cavazzini:Pfize: Honoraria; Incyte: Honoraria; Novartis: Honoraria. Bonifacio:Pfizer: Honoraria; Incyte: Honoraria; Novartis: Honoraria; Amgen: Honoraria; BMS: Honoraria. Crugnola:Incyte: Honoraria; Novartis: Honoraria. Cuneo:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Krampera:Novartis: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Cavo:amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; takeda: 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; sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; bms: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; novartis: Honoraria. Breccia:Celgene: Honoraria; Incyte: Honoraria; Pfizer: Honoraria; BMS: Honoraria; Novartis: Honoraria. Palumbo:Hospira: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Teva: Honoraria; Novartis: Honoraria; Celgene: Honoraria. Palandri:Novartis: Consultancy, Honoraria.

Abstract: Cytopenic myelofibrosis has a lower probability of therapeutic success with ruxolitinib as monotherapy and worse outcome. Patients with cytopenic myelofibrosis should be considered for alternative therapeutic strategies.

Abstract: Infections represent one of the major concerns regarding the utilization of ruxolitinib (RUX) in patients with myelofibrosis. With the aim to investigate epidemiology, outcome and risk factors for infections in RUX‐exposed patients, we collected clinical and laboratory data of 446 myelofibrosis patients treated with RUX between June 2011 and November 2016 in 23 European Hematology Centers. After a median RUX exposure of 23.5 months (range, 1‐56), 123 patients (28%) experienced 161 infectious events (grades 3‐4 32%, fatal 9%), for an incidence rate of 17 cases per 100 pts/y. The rate of infections tended to decrease over time: 14% of patients developed the first infection within 6 months, 5% between 6 and 12 months, 3.7% between 12 and 18 months, 3.4% between 18 and 24 months, and 7.9% thereafter ( P   〈  .0001). Respiratory tract infections were more frequently observed (81 events, 50%), and bacteria were the most frequent etiological agents (68.9%). However, also viral (14.9%) and fungal infections (2.5%) were observed. In multivariate analysis, previous infectious event (HR 2.54; 95% CI, 1.51‐4.28; P  = .0005) and high international prognostic score system category (IPSS) (HR 1.53; 95% CI, 1.07‐2.20; P  = .021) significantly correlated with higher infectious risk. On the contrary, spleen reduction ≥50% from baseline after 3 months of treatment ( P  = .02) was associated with better infection‐free survival. Taken together, these findings reinforce the concept of disease severity as the most important risk factor for infections, and describe, for the first time, that a positive therapeutic effect in reducing splenomegaly may also reduce subsequent infectious complications.

Abstract: Ruxolitinib (RUX), the first JAK1/JAK2 inhibitor approved for myelofibrosis (MF) therapy, has recently been associated with the occurrence of second primary malignancies (SPMs), mainly lymphomas and non‐melanoma skin cancers (NMSCs). We analyzed the incidence, risk factors and outcome of SPMs in 700 MF patients treated with RUX in a real‐world context. Median follow‐up from starting RUX was 2·9 years. Overall, 80 (11·4%) patients developed 87 SPMs after RUX start. NMSCs were the most common SPMs (50·6% of the cases). Multivariate analysis demonstrated that male sex [hazard ratio (HR): 2·37, 95% confidence interval (95%CI): 1·22–4·60, P  = 0·01] and thrombocytosis 〉  400 × 10 9 /l at RUX start (HR:1·98, 95%CI: 1·10–4·60, P  = 0·02) were associated with increased risk for SPMs. Risk factors for NMSC alone were male sex (HR: 3·14, 95%CI: 1·24–7·92, P  = 0·02) and duration of hydroxycarbamide and RUX therapy  〉  5 years (HR: 3·20, 95%CI: 1·17–8·75, P  = 0·02 and HR: 2·93, 95%CI: 1·39–6·17, P  = 0·005 respectively). In SPMs excluding NMSCs, male sex (HR: 2·41, 95%CI: 1·11–5·25, P  = 0·03), platelet  〉  400 × 10 9 /l (HR: 3·30, 95%CI: 1·67–6·50, P  = 0·001) and previous arterial thromboses (HR: 3·47, 95%CI: 1·48–8·14, P  = 0·004) were shown to be associated with higher risk of SPMs. While it is reassuring that no aggressive lymphoma was documented, active skin surveillance is recommended in all patients and particularly after prolonged hydroxycaramide therapy; oncological screening should be triggered by thrombocytosis and arterial thrombosis, particularly in males.

Abstract: Introduction. Blast phase (BP) is the terminal and most incurable phase of myelofibrosis (MF) and occurs in a not negligible fraction of patients (pts). In the pre-ruxolitinib (RUX) era, peripheral blasts, thrombocytopenia, unfavorable cytogenetics, and high risk category were identified as predictors of BP. RUX is the standard of care for symptomatic MF; however, information on clinical/laboratory correlates of BP in RUX-treated pts is not available. Aims. The primary objective of the study is to assess real-world data on incidence, risk factors and outcome of BP in RUX-treated MF pts. Methods. A multicentre observational retrospective study on RUX-treated MF pts was conducted in 20 European Hematology Centers. Data were extracted from an electronic database that included consecutive pts treated with RUX from June 2011. Data cut-off was June 2019. Risk category was assessed at RUX start according to the Dynamic International Prognostic Score System (DIPSS) or the Myelofibrosis Secondary to PV and ET Collaboration Prognostic Model (MYSEC-PM) in pts with post-Polycythemia Vera (PV)/post-Essential Thrombocythemia (ET) MF (secondary MF, SMF). A time-to-event (BP) analysis was conducted with Fine & Gray model with death/time of stem cell transplant as competing risks. Variables tested for association with BP were: age≥65yr, sex, transfusion-dependency, PLT 〈 150x109/l, peripheral blasts ≥3%, marrow fibrosis grade, CALR-unmutated genotype, unfavorable karyotype, spleen length (≥10 cm), total symptoms score (≥20), previous hydroxyurea (HU), alkylating agents, and interferon (IFN) use, time from MF diagnosis to RUX start, and PV/ET duration. Cumulative Incidence Function among risk categories for DIPSS and MYSEC-PM was calculated applying the Gray's model. Results . Overall, 589 MF pts were included and observed for 1833 pt-yrs from RUX start (median, 35.4 mos). Diagnosis was PMF in 304 pts (51.6%), PPV-MF in 164 pts (27.8%) or PET-MF in 121 (20.6%); 58.4% males. Molecular status was: JAK2V617F (82.5%), CALR (11.3%) and MPLW515K/L (1.1%); 5.1% were triple negatives. Overall, 368 (62.5%) pts received ≥1 cytoreductive therapy before RUX, specifically: HU, n. 357; alkylating agents, n. 47; anagrelide, n. 33; and IFN, n. 29. Median time from MF diagnosis to RUX start was 1.3 yrs. DIPSS for the whole cohort was: INT-1 (52.9%), INT-2 (40.1%), and HIGH (7%). DIPSS distribution in PMF pts was: INT-1 (47.8%), INT-2 (45.7%), and HIGH (6.5%), while SMF pts were categorized at LOW (11.1%), INT-1 (43.1%), INT-2 (31.2%) and HIGH (14.6%) risk according to the MYSEC-PM. Overall, 65 (11%) developed BP. In 61 pts, BP caused RUX withdrawal after a median time of 1.2 yrs (0.7-6.2); in 4 pts BP occurred after RUX stop (median time: 2.4 yrs). BP incidence rate was 3.6 x100 pt-yrs and was comparable in PMF and SMF (p=0.1). In univariate analysis, the probability of BP evolution for the PMF cohort was significantly reduced by previous IFN use (p=0.001). In SMF, predictors for BP in univariate analysis were PLT 〈 150 x109/l (p=0.001), blasts ≥3% (p=0.002), grade 3 marrow fibrosis (p=0.03) and PV/ET duration ≥ 10 yrs (p=0.02); previous IFN significantly reduced the risk of BP (p=0.02). In multivariable analysis, PLT 〈 150 x109/l (HR 2.4, 95% CI 1.1-5.4, p=0.03), blasts ≥3% (HR 3.3, 95% CI 1.4-7.5, p=0.004) and previous IFN (HR 0.1, 95% CI 0.02-0.8, p=0.04) remained significant. High DIPSS risk significantly predicted BP in PMF (p=0.04, HR [95% CI]: 2.6 [1.1-6.5] ) but not in SMF (p=0.40). In this latter cohort, only the MYSEC-PM was associated with BP (p=0.02, HR 1.7 [95% CI]: [1.1-2.8] ) (Fig.1). Estimated HRs, in reference to the lower score category, were: 1.10 for INT-1, 1.82 for INT-2, and 4.04 for HIGH risk. HR for HIGH risk, comparing to all lower risk groups, was 3.53 (95% CI: 1.53-8.11). Overall, 54 (81.8%) BP pts died and median survival was 2.8 mos. Survival after BP was not influenced by type of MF, previous response to RUX, and type of salvage treatment. Conclusions. Thrombocytopenia and peripheral blasts at RUX start identified pts at higher risk of BP in SMF, while previous IFN use was associated with reduced BP evolution in both PMF and SMF, suggesting a possible disease-modifying action of this agent. Also, this analysis supports the ability of MYSEC-PM in predicting BP in pts with SMF. Despite RUX use, outcome after BP remained dismal, confirming the need for newer treatment strategies. Disclosures Palandri: Novartis: Consultancy, Honoraria. Breccia:Incyte: Honoraria; Celgene: Honoraria; Novartis: Honoraria; Pfizer: Honoraria; BMS: Honoraria. Tiribelli:Incyte: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. Benevolo:Novartis Pharmaceuticals: Consultancy. Bonifacio:Novartis: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; Incyte: Honoraria; BMS: Honoraria. Iurlo:Pfizer: Honoraria; BMS: Honoraria; Incyte: Honoraria; Novartis: Honoraria. Elli:Novartis: Membership on an entity's Board of Directors or advisory committees. Abruzzese:BMS: Consultancy; Incyte: Consultancy; Novartis: Consultancy; Pfizer: Consultancy. Sgherza:Novartis: Honoraria; BMS: Honoraria; Pfizer: Honoraria; Incyte: Honoraria. Cavazzini:Pfize: Honoraria; Incyte: Honoraria; Novartis: Honoraria. Crugnola:Novartis: Honoraria; Incyte: Honoraria. Isidori:Janssen: Honoraria; Novartis: Honoraria; Gilead: Honoraria. Heidel:Novartis: Consultancy, Research Funding; Celgene: Consultancy; CTI: Consultancy. Latagliata:Janssen: Honoraria; Novartis: Honoraria; Pfizer: Honoraria; Celgene: Honoraria. Trawinska:Novartis: Consultancy, Honoraria. Krampera:Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Cuneo:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau; Amgen: Honoraria, 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; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; 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. Palumbo:Novartis: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria; Hospira: Honoraria; Teva: Honoraria.