Abstract: The Greek Registry of Essential Thrombocythemia (ET) is implemented under the auspices of the Acute Leukemias and Myeloproliferative Neoplasms Study Group of the Hellenic Society of Haematology. Hereby, we present results after four years of retrospective data collection. The total number of patients included is 1078, from 14 Greek sites; ET was diagnosed between 1982 and 2012. The male to female ratio is 1:1.19. Median age at diagnosis is 63 years, median platelet counts (PLT) 826x109/L, hemoglobin (Hb) 13.6 g/dL, white blood cell counts (WBC) 9.4x109/L. The presenting symptoms were a thrombotic event in 6.8%, a hemorrhagic event in 1.5% of patients. In 79.8% of the patients the diagnosis was made after incidental finding of elevated platelet counts on routine laboratory investigation. Molecular studies were performed in 677 patients and 42.8% of them were positive for the JAK2-V617F mutation. The presence of JAK2-V617F mutation (mutant vs wild type allele) was associated with baseline platelet counts (757.5 vs 882 x109/L) and hemoglobin levels (14.4 vs 13.4 g/dL), p 〈 0.001 (Mann-Whitney U-test). A history of thrombosis or hemorrhage was present in 18.6% and 6.6% of patients respectively. Chi-square test was performed to assess whether platelet counts at diagnosis ( 〈 600, 600-800, 〉 800 x109/L), Hb 〈 13.8g/dL, WBC 〉 9.5x109/L, or splenomegaly are associated with thrombotic or hemorrhagic events in the past medical history or during the follow-up of ET patients. The only statistically significant difference was observed in the occurrence of thrombosis during the follow up: 10.1% of those with PLT between 600-800 x109/L, 4.5% in PLT 〈 600 and 5.6% in PLT 〉 800 x109/L. To assess for possible confounders the multivariable logistic regression model was used, with independent variables the PLT at diagnosis, age 〉 60 years, history of thrombosis and first line therapy. The history of thrombosis was the only statistically significant risk factor with odds ratio (OR) 3.9 (p=0.0005), while PLT was not a statistically significant risk factor (OR=2.5, p=0.074). Antiplatelet therapy was offered in 80% of patients (aspirin in 59.1%, clopidogrel in 4.7%, and combination therapy in 6.5%); anticoagulants (low molecular weight heparin or warfarin) were given in 2.3%, while the remaining 17.8% of patients did not receive any antithrombotic therapy. During the first six months post diagnosis, 31.6% of patients did not need any cytoreductive therapy. The rest 68.4% of the patients received first line therapy (hydroxyurea 80.6%, anagrelide 11.4% and interferon 5.4%). The response rates were 89.9%, 82.1% and 85.7%, respectively. Second-line therapy was received by 25.8% of the patients (hydroxyurea 23%, anagrelide 44.6%, interferon 9.5%), while the off-label combination of hydroxyurea and anagrelide was administered to 21.2% of the patients. Of the 852 patients treated with hydroxyurea as first line therapy, 12.1% switched to anagrelide and 1.2% to interferon. Of those initially treated with anagrelide, 27.6% switched to hydroxyurea and 8.2% to interferon. During the follow up phase, secondary solid tumor occurred in 4% and hematological malignancy in 2.7% of the patients. The aim of the registry and the subsequent data analysis is to convey the practice of managing the disease. Moreover, useful conclusions can be reached regarding to the patients’ responsiveness to therapy and the minimization of thrombotic and hemorrhagic adverse events. Disclosures: Spanoudakis: Genesis Hellas: Honoraria. Kotsianidis:Genesis Hellas: Honoraria, Research Funding.

Abstract: Waldenström's Macroglobulinemia (WM) is an indolent lymphoma with heterogeneous clinical presentation and prolonged course. In this context, determining the overall disease and therapy burden in terms of complications and associated comorbidities is necessary. Of special interest is the occurrence of a second malignancy and transformation to high grade lymphoma, due to their impact on survival and quality of life but also on health resource use and follow up strategies. Several factors including immune dysfunction, genetic predisposition, environmental factors and treatment effects have been suggested as possible underlying pathophysiologic mechanisms for development of second primary malignancies or transformation in patients with WM. While there have been data published from various series, it is crucial to have data after prolonged follow up, as the time for development of such complications may be long. The current study included all patients with symptomatic WM that have been registered in the prospectively maintained database of the Greek Myeloma Study Group, in which the development of a second malignancy and disease transformation is being recorded, including type of second cancer and date of diagnosis. All patients fulfilled criteria for symptomatic WM diagnosis and for treatment initiation according to the Consensus Recommendations. The analysis included 598 symptomatic newly diagnosed patients with WM with a median follow up of 114 months. The median age was 69 years and 284 (47%) have died. Primary therapy was rituximab-based in 65%, contained alkylating agents in 78%, a nucleoside analogue in 2% and an anthracycline in 4%. In 46 patients (7.7%) the diagnosis of a second tumor was made after the initiation of treatment for symptomatic WM. The most common malignancies were cancer of the prostate (18%), stomach (6%), colon (6%), lung (6%), pancreas (3%), non-melanoma skin (3%) and central nervous system (6%) and AML/MDS (6%). In addition, in 12 (2%) patients, a diagnosis of another malignancy preceded the diagnosis of WM. The median time from treatment initiation for symptomatic WM to the diagnosis of a second primary malignancy was 51 months [interquartile range (IQR): 16-79] . The incidence ratio (IR) of a second primary malignancy was 0.0095 per person-years and the cumulative incidence of a second primary malignancy, accounting for death due to WM or other causes as a competing event, at 5 and 10 years was 3.6% and 6.6%, while, the risk of death from WM or other causes was 22.5% and 46%, respectively (Figure). The IR of a second malignancy was higher in men [IR ratio (IRR): 0.5, 95% CI 0.2-1.1, p=0.067] while it was similar for younger vs older patients ( 〉 75 years) (IRR: 1.57, 95% CI 0.61-3.5, p=0.27). Importantly, the use of rituximab as primary treatment was not associated with any increased risk of a second malignancy (IRR: 0.99, 95%CI 0.5-2.1, p=0.97). The incidence of second malignancies has not changed significantly in the era before vs after 2000. Overall, 19 (3.1%) transformation events were identified; the median time from treatment initiation to transformation was 51 months (IQR: 28-106). The IR for transformation was 0.005 per person-years and the cumulative risk for transformation, accounting for death of any cause as a competing event, was 2.2% and 3.6% at 5 and 10 years respectively. The presence of anemia (hemoglobin 〈 11.5 gr/dl) at diagnosis was associated with increased risk of transformation (IRR: 6.75, 95% CI 1.06-50, p=0.02), while the use of rituximab in first line therapy decreased transformation risk (IRR: 0.36, 95% CI 0.11-1, p=0.041). Interestingly the incidence of transformation decreased after 2000 (IRR: 0.23, 95% 0.07-0.69, p=0.0035). We found no increased risk of transformation among patients that received alkylating agents in their primary therapy; the numbers of patients that received primary therapy with nucleoside analogues was small, however no increased risk was identified. We conclude that the incidence of a second malignancy among patients with symptomatic WM is 7.7%, corresponding to an incidence rate of about 1 case per 100 patients per year. Transformation occurred in 3.1% corresponding to an incidence rate of 0.5 cases per 100 patients per year; this risk was higher among patients presenting with anemia and has been reduced after 2000. This may be related to the extensive use of rituximab and less frequent use of alkylating agents and nucleoside analogues. Figure. Figure. Disclosures Kastritis: Takeda: 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; Prothena: 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. Terpos:Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: member of steering committee, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grant, Research Funding; BMS: Consultancy; Novartis: Consultancy; Genesis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grant, Research Funding; Amgen Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grant, steering committee member, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: member of DMC, Research Funding. Dimopoulos:Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria; Amgen: Honoraria.

Abstract: Introduction: Pomalidomide (POM) plus low-dose dexamethasone (POM/LoDex) is a standard of care for patients with relapsed/refractory multiple myeloma (RRMM), who have received ≥2 prior therapies, including lenalidomide (LEN) and bortezomib (BORT). In view of the limited real-world evidence on POM/LoDex effectiveness, this study aimed to provide insight into progression-free survival (PFS), response to treatment and drug utilization patterns in the routine clinical practice in Greece. Methods: 'POWERFUL' (NCT03353545) was a non-interventional, multicenter, retrospective and prospective study of adult RRMM patients, initiated on POM/LoDex between 01-Jan-2016 and 28-Feb-2019 per the approved label. Patients who had received up to one POM/LoDex cycle were consecutively enrolled between 16-Nov-2017 and 21-Feb-2019 (prospective recruitment phase). One month prior to completion of this phase, aiming to facilitate recruitment of the target size, patients, whose treatment with POM/LoDex was ongoing but & gt;1 cycles had been received or for whom treatment was discontinued, were consecutively enrolled in reverse chronological order, based on POM/LoDex start date (retrospective recruitment). Patients were observed until the earliest point of disease progression (PD), death, informed consent (IC) withdrawal, treatment discontinuation for reason other than PD or start of next antimyeloma therapy, physician's decision, or last patient enrolled plus up to 12 months of treatment. IC or consent waiver for deceased subjects was obtained. Safety data were collected prospectively. Results: Eligible patients (N=99; 75 with prospective and 24 with a purely retrospective follow-up) were recruited by 18 hematology departments. The median (IQR) observation period was 8.8 (4.2-15.4) months. Baseline patient characteristics are presented in Table 1. Fifty patients (50.5%) started POM/LoDex as third-line treatment. POM was initiated at 4 mg/day on days 1-21 every 28 days in 75.8% of the patients. A median of 8 (range: 1-38) cycles were received at a median POM dose of 4 mg/day (range: 1-4), over 8.3 (range: 0.3-47.6) months. The POM dose reduction and interruption rates were 28.3% and 59.6%, respectively. Of the patients, 37.4% were treated for ≥ one year. Treatment was discontinued in 81.8%, due to PD (56.8%), safety reasons (22.2%), death (6.2%), other reasons (9.9%), and due to loss of follow-up (4.9%). The investigator-assessed overall response rate (≥partial response [PR]) was 32.3%; best response rates were: stringent complete or complete response (7.1%), very good PR (8.1%), PR (17.2%), minimal response (11.1%), stable disease (21.2%), PD (12.1%), and non-evaluable response (23.2%). Median time to response and duration of response in patients achieving ≥PR was 3.2 [95% confidence interval (CI): 2.6-3.6] and 15.8 (95%CI: 11.3-not reached) months, respectively. Over a Kaplan-Meier estimated median follow-up of 13.8 months, the median PFS was 10.5 months (95%CI: 7.4-14.4) [13.0 vs. 8.8 months for patients treated in the third vs. the fourth- and beyond line (log-rank p=0.494), and 13.0 vs. 8.8 months for patients treated with POM/LoDex only vs. those co-administered other antimyeloma agents (log-rank p=0.411)]. The estimated 6-, 12-, 24- and 36-month PFS rates were 70.3%, 48.3%, 20.1% and 12.0%, respectively. Multivariate Cox regression analysis of the impact of baseline characteristics on PFS indicated male sex [hazard ratio (HR)=2.08; 95%CI: 1.12-3.89; p=0.021] and higher than normal serum lactate dehydrogenase levels (HR=2.84; 95%CI: 1.39-5.81; p=0.004) as negative predictors of PFS. Over a median safety data collection period of 7.6 months (range: 0.4-18.6), the POM-related adverse events (ADR) incidence rate in the safety-evaluable population (i.e., 75 patients with prospective follow-up) was 42.7% (73 events). Only neutropenia (13.3%) was reported at a frequency ≥10%. The serious ADR rate was 18.7%, whereas grade ≥ 3 hematological and non-hematological ADR rates were 8.0%, and 5.3%, respectively. Conclusion: In this Real-World dataset from Greek centers, POM/LoDex, administered in the third-line and beyond setting of RRMM, displayed a longer PFS than in controlled clinical trials, which was not impacted by the treatment line and concurrent receipt of other antimyeloma agents. About one-third of patients achieved at least PR with an about 16-month response duration. Disclosures Terpos: Amgen: Honoraria, Research Funding; Sanofi: Honoraria; Celgene: Honoraria; Takeda: Honoraria, Other: travel expenses , Research Funding; Janssen: Honoraria, Research Funding; Genesis pharma SA: Honoraria, Other: travel expenses , Research Funding; BMS: Honoraria. Repousis:Genesis pharma SA: Membership on an entity's Board of Directors or advisory committees, Research Funding. Hatjiharissi:Roche: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genesis pharma SA: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Honoraria; Gilead: Membership on an entity's Board of Directors or advisory committees. Assimakopoulou:Genesis pharma SA: Research Funding. Vassilopoulos:Abbvie: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Genesis pharma SA: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Research Funding. Pouli:Genesis pharma SA: Research Funding. Spanoudakis:Genesis pharma SA: Research Funding. Michali:Takeda: Research Funding; Genesis pharma SA: Research Funding. Pangalis:Genesis pharma SA: Research Funding. Poziopoulos:Genesis pharma SA: Research Funding. Kyrtsonis:Genesis pharma SA: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; 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. Pappa:Genesis pharma SA: Research Funding. Symeonidis:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GenesisPharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck Sharp & Dohme: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; WinMedica: Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Research Funding; Astellas: Research Funding; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi/Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Georgopoulos:Genesis pharma SA: Research Funding. Zikos:Genesis pharma SA: Membership on an entity's Board of Directors or advisory committees, Research Funding. Papadaki:Genesis pharma SA: Membership on an entity's Board of Directors or advisory committees, Research Funding. Dadakaridou:Genesis pharma SA: Research Funding. Karvounis-Marolachakis:Genesis pharma SA: Current Employment. Patos:Genesis pharma SA: Current Employment. Katodritou:Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Theagenion Cancer Hospital: Current Employment; Takeda: Honoraria, Other: Expenses, Research Funding; Genesis Pharma: Honoraria, Other: Expenses, Research Funding; Abbvie: Research Funding; Karyopharm: Research Funding.