Stockholm, Sweden, June 13–16, 2013

Myelodysplastic syndromes - Clinical 1Hopital Henri Mondor, Creteil, 2Hopital Saint Louis, 3Hopital Cochin, Paris, 4CHU, Nantes, 5Centre Henri BECQUEREL, Rouen, 6Hôpital Saint Vincent de Paul, Lille, 7CHU Purpan, Toulouse, 8Hôpital de la Cote Basque, Bayonne, 9CHU Brabois, Vandoeuvre, 10 CHU, Nimes, 11 CHU, Dijon, 12 CHU, Le Mans, S1106 13 CHU, Clermont Ferrand, 14 CHU, Limoges, 15 CH, Avignon, 16 CH, Perpignan, 17 Hopital Avicenne, Bobigny, France IS IT POSSIBLE TO CURE SEVERE APLASTIC ANEMIA REFRACTORY TO IMMUNOSUPPRESSIVE THERAPY WITHOUT TRANSPLANT? A LONG Background: ESAs, the first line treatments of anemia in non del 5q lower risk TERM FOLLOW UP ANALYSIS OF A PHASE II STUDY OF ELTROMBOPAG R Desmond 1,* , D Townsley 1, M Olnes 2, P Scheinberg 3, B Dumitriu 1, A Parikh 4, MDS, yield only 40-50% responses. LEN gives RBC transfusion independence K Broder 1, K Calvo 5, C Wu 6, N Young 1, C Dunbar 1 (TI) in about 25% of ESA resistant (or relapsing) TD lower risk MDS without del 1Hematology, National Heart Lung and Blood Institute, Bethesda, 2Hematology, 5q (Raza, Blood, 2008), and a gene expression signature can predict response Alaska Native Medical Center, Anchorage, United States, 3Hospital Sao Jose (Ebert, Plos Med 2008). - Hospital Beneficencia Portuguesa de Sao Paulo, Sao Paulo, Brazil, 4Eastern Aims: We randomized in this patient population LEN alone and LEN+EPO. Regional Medical Center, Philadelphia, 5Laboratory Medicine, National Institute Methods: In this prospective multicenter open-label phase II study of Health, 6Biostatistics Research, National Heart Lung and Blood Institute, (NCT01718379), lower risk MDS patients without del 5q, with TD (≥4 RBC units Bethesda, United States during the previous 8 weeks (w)) and with ESA resistance or relapse after a response were randomized between LEN alone, 10mg/d ¥ 21 d/4 w (L arm) or LEN (same schedule)+EPO beta, 60 000 U/w (LE arm). The primary endpoint Background: About one quarter of patients with severe aplastic anemia are refractory to immunosuppressive therapy. Management of this population is was erythroid response (HI-E, IWG 2006 criteria) after 4 treatment cycles. Sec - challenging with no standard therapies available. Our group has shown that ondary objectives included identification of biomarkers of response. eltrombopag has good efficacy with minimal toxicity in this setting (Olnes MJ Results: Between July 2010 and June 2012, 132 patients (pts, 66/arm), medi - NEJM 2012; 367:11-19). In this pilot, phase II, non-randomized study patients an age 73 (range 46-88), M/F: 88/44 were enrolled. Median TD was 6 RBC received eltrombopag at a dose of 50 mg with dose escalation every 2 weeks units/8w (range 2-18). IPSS was Low in 45% and Int-1 in 55% pts. Pretreatment to a maximum of 150 mg. The primary endpoint was improvement in blood characteristics did not differ between the 2 groups. All but 3 pts, who withdrew counts with defined responses for each lineage. Forty-four per cent (11/25) of consent (2L+1LE), were evaluable for response. In this ITT population, HI-E was patients had a hematological response after 12-16 weeks, with responses in all obtained in 15 pts (23.4%) in L arm and 26 (40.0%) in LE arm (RR=1.7, three lineages seen. The majority of responders became transfusion-independ - P=0.043, chi2 test), and TI in 9 (14.1%) versus 16 (24.6%) pts (RR=1.7, ent for platelets (9/11), 6 had erythroid responses with 3 patients previously P=0.13). In the 99 pts who completed 4 treatment cycles, 41 achieved HI-E, dependent on red cell transfusion becoming transfusion -independent. Nine of including 15/49 (30.6%) in L arm versus 26/50 (52.0%) in LE arm (P=0.03), and 11 responders had increased neutrophil counts. TI in 9 (18.4%) versus 16 (32.0%) pts (RR=1.7, P=0.12). Side effects (cytope - Aims: The aim of this analysis is to report updated safety and efficacy data in nias and 1 DVT/arm) were similar in the 2 arms. A 29-gene expression profile a larger patient cohort, and ask whether eltrombopag can be discontinued in signature predicting HI-E to L or LE, different from that previously published, patients with severe aplastic anemia achieving robust count recovery. was identified and a polymorphism in the CRBN gene (Kosmider, submitted) Methods: This current analysis includes 37 patients with refractory severe was significantly associated with HI-E in the entire cohort (P=0.034) aplastic anemia, including 25 from the initial cohort and an additional 12 Summary and Conclusions: LEN+EPO yielded a significantly better erythroid patients, enrolled in a second cohort of 18 patients, who have reached time to response than LEN alone in lower risk MDS patients with anemia resistant to response assessment. Patients reaching response criteria at 12-16 weeks were ESA alone. A gene expression signature and a CRBN gene polymorphism cor - offered continued therapy in an extended access study. Patients with robust related with the erythroid response. blood count recovery (platelets >50,000/ul, Hb >10 gr/dL in the absence of RBC transfusion, and neutrophils >1,000/ul for more than 8 weeks) had eltrom - bopag tapered and discontinued. S1108 Median age was 44 years (range 18-77). Median number of prior Results: PLACEBO-CONTROLLED, RANDOMIZED, PHASE I/II TRIAL OF THE courses of immunosuppression was 2 (range 2-4) and median time since last THROMBOPOIETIN RECEPTOR AGONIST ELTROMBOPAG IN THROM - immunosuppression was 10 months (range 6-55). Thirty-eight per cent (14/37 BOCYTOPENIC PATIENTS WITH ADVANCED MYELODYSPLASTIC SYN - patients) had a response in at least one lineage: 10 patients had platelet DROMES OR ACUTE MYELOID LEUKEMIA responses; 8 had erythroid responses, and 9 neutropenic patients had U Platzbecker 1,* , R Wong 2, A Verma 3, C Abboud 4, S Araujo 5, T Chiou 6, increased neutrophil counts. One non-responder who had drug stopped prema - J Feigert 7, S Yeh 8, K Götze 9, N Gorin 10 , P Greenberg 11 , S Kambhampati 12 , turely because of hepatitis B infection was retreated off protocol and attained Y Kim 13 , J Lee 14 , R Lyons 15 , M Ruggeri 16 , V Santini 17 , G Cheng 18 , J Jang 19 , red cell- and platelet-transfusion independence. Of the 11 patients who entered C Chen 20 , S Dougherty 21 , F Mannino 21 , Y Kamel 22 , G Chan 21 , M Arning 21 , the extension study, 7 have and continue to maintain trilineage responses. We N Stone 21 , A Giagounidis 23 discontinued study drug because of sustained and robust counts (platelets 1Universitätsklinikum Carl Gustav Carus, Dresden, Germany, 2Prince of Wales >50,000uL, Hb >10 gr/dL in the absence of transfusion and neutrophils >1,000 Hospital, Shatin, Hong Kong, 3Albert Einstein College of Medicine, Bronx, for more than 8 weeks) in 4/7 patients and all have maintained stable counts 4Washington University Medical School, St. Louis, United States, 5Hospital das with a median follow up of 7.5 months (range 7-9) off drug. Five non-respon - Cl ίnicas-UFMG, Sao Paulo, Brazil, 6Taipei Veterans General Hospital, Taipei, ders had cytogenetic evolution, all found at response assessment with 3 devel - Taiwan, 7Virginia Cancer Specialists, Arlington, United States, 8China Medical oping monosomy7, 1 trisomy 21, and 1 trisomy 8. A 77 year old male who was University Hospital, Taichung, Taiwan, 9Technical University of Munich, Munich, enrolled in the extended access study with a non-robust response developed Germany, 10 Hôpital Saint-Antoine, Paris, France, 11 Stanford University Cancer monosomy 13 after 14 months on eltrombopag. Baseline reticulocytes counts Center, Stanford, 12 Kansas City VA Medical Center, Kansas City, United States, continued to be predictive of response (45.22 per cubic millimeter in respon - 13 St. Mary’s Hospital, 14 Asan Medical Center, Seoul, Korea, Republic of Korea, ders vs. 24.45 per cubic millimeter in non-responders, P=0.015). There was no 15 Cancer Care Centers of South Texas, San Antonio/US Oncology, San Anto - increased reticulin noted in bone marrow biopsies performed at response nio, United States, 16 San Bortolo Hospital, Vicenza, 17 AOU Careggi, Universi - assessment and thereafter every 6 months on drug. ty of Florence, Florence, Italy, 18 Chinese University of Hong Kong, Shatin, Summary and Conclusions: Eltrombopag is an effective treatment for refrac - Hong Kong, 19 Samsung Medical Center, Seoul, Korea, Republic of Korea, tory severe aplastic anemia. Continued exposure to drug may not be required 20 National Taiwan University Hospital, Taipei, Taiwan, 21 GlaxoSmithKline, Col - for a sustained remission in those with robust count recovery. As in all patients legeville, United States, 22 GlaxoSmithKline, Stockley Park, United Kingdom, with BM failure syndromes, serial BM biopsies are recommended to monitor for 23 cytogenetic or morphologic evolution. Patients treated with eltrombopag for Marienhospital, Düsseldorf, Germany marrow failure states should be enrolled in clinical trials to allow data collection regarding risk of progression to clonal hematopoiesis. We are currently inves - Background: Patients (pts) with advanced myelodysplastic syndrome (MDS) tigating patients who evolved with comparative genomic hybridization to assess or acute myeloid leukemia (AML) often develop platelet (plt) transfusion- whether unbalanced chromosomal abnormalities existed prior to treatment. dependent thrombocytopenia. Eltrombopag (EPAG), an oral thrombopoietin receptor agonist, increases plts in chronic immune thrombocytopenia, hepati - tis C virus-associated thrombocytopenia, and severe aplastic anemia. To evaluate the safety and tolerability of EPAG in thrombocytopenic pts S1107 Aims: with advanced MDS and AML (primary end point). Secondary end points A RANDOMISED STUDY OF LENALIDOMIDE (LEN) +/- EPO IN RBC include plt transfusions, plt response, and overall survival (OS). TRANSFUSION DEPENDENT (TD) IPSS LOW AND INT-1 (LOWER RISK) Methods: Pts with relapsed/refractory MDS or AML ineligible for antileukemic MYELODYSPLASTIC SYNDROMES (MDS) WITHOUT DEL 5Q RESISTANT therapies, with 10%>50% bone marrow (BM) blasts and plts <30 Gi/L were TO EPO randomized 2:1 to EPAG 50 mg qd (increases q2 weeks in pts without a plt A Toma 1,* , S Chevret 2, O Kosmider 3, J Delaunay 4, A Stamatoullas 5, C Rose 6, response, up to 300 mg [150 mg for Asian pts]) or placebo (PLB) for 6 months. O Beyne-Rauzy 7, A Banos 8, A Guerci-Bresler 9, E Jourdan 10 , V Sardnal 3, Standard supportive care and disease-modifying treatments were permitted at D Caillot 11 , K Laribi 12 , B de Renzis 13 , D Bordessoule 14 , B Slama 15 , L Sanhes 16 , the investigator’s discretion. M Fontenay 3, P Fenaux 17 , F Dreyfus 3 Results: Overall, 98 pts were enrolled (EPAG: n=64; PLB: n=34). Most pts had

haematologica | 2013; 98(s1) | 455 18 th Congress of the European Hematology Association

AML (Table 1) and received ≥1 prior antileukemic treatments, including aberrancies in antigen expression remains to be clarified yet. hypomethylating agents (EPAG: 24 [38%]; PLB: 11 [32%]) and chemotherapy Aims: Evaluate the respective impact of distinct aberrancies in antigen expres - (EPAG: 10 [16%]; PLB: 3 [9%]). Most pts received the maximum dose (EPAG: sion on overall survival (OS) in pts with suspected MDS in relation to cytomor - 36 [56%]; PLB: 20 [59%]). Mean treatment duration was 102 days for EPAG and phology (CM) and cytogenetics (CG). 78 days for PLB; 9 (14%) pts on EPAG continued treatment >6 mo versus 1 (3%) Methods: 804 pts with suspected MDS were analyzed in parallel by CM, CG pt on PLB. Twenty-one (33%) EPAG and 17 (50%) PLB pts died on therapy or and MFC (median age 70 yrs, range 2-89; median OS 6.2 yrs, median follow- <30 days from the last dose; primary cause of death in both arms was underly - up 3.2 yrs). Results of CM indicated MDS in 493 (61.3%) pts; in 170 (21.1%) ing disease. The most common (≥20% in the EPAG arm) adverse events (AEs) pts CM revealed evidence of dysplasia but which was not sufficient to diagnose on therapy +30 days were pyrexia, nausea, diarrhea, fatigue, decreased appetite, MDS; CM excluded MDS in 141 (17.5%) pts. Karyotypes were good/interme - and pneumonia. Serious AEs in ≥5% of pts in either arm included sepsis, pyrex - diate/poor according to IPSS in 684 (85.1%)/89 (11.1%)/31 (3.9%) pts. MFC ia, febrile neutropenia, and pneumonia. Hepatobiliary events were reported in 11 was performed following ELN recommendations (Westers, Leukemia 2012) in (17%) EPAG and 5 (15%) PLB pts; 3% (EPAG: 2; PLB: 1) reported thromboem - myeloid progenitor cells (MPC), granulocytes, monocytes and erythroid cells. bolic events. Of 26 pts with MDS (WHO criteria) at baseline, 14 (EPAG: 9; PLB: MFC parameters included increased or decreased antigen expression, expres - 5) had postbaseline BM examination results available; 8 (EPAG: 5 [56%]; PLB: sion of normally not expressed antigens, aberrant expression pattern of anti - 3 [60%]) of 14 pts developed BM blasts ≥20% during treatment. Plt transfusion gen pairs and expression of lymphatic antigens. independence for ≥8 weeks was reported for 24 (38%) EPAG and 7 (21%) PLB Results: The first set of analyses is based on the total of 804 pts, i.e. regard - pts ( P=0.0979). Ten (16%) EPAG and 9 (26%) PLB pts had ≥Grade 3 hemor - less of confirmation of MDS by CM. 11 MFC parameters were significantly rhages ( P=0.1472). More EPAG versus PLB pts started antileukemic/palliative associated with OS: MPC >5% (P<0.001, hazard ratio (HR) 2.5), expression treatment during the study (26 [41%] versus 11 [32%], respectively), including of CD5 (P<0.001, HR 4.1), CD56 (P=0.043, HR 2.0), CD7 (P=0.015, HR 2.2) hypomethylating agents and salvage chemotherapy. Median OS was 27 weeks in MPC; reduced side-scatter signal (P<0.001, HR 1.9), aberrant CD13/CD16 for EPAG versus 15.7 weeks for PLB (hazard ratio=0.71, P=0.1931). During expression pattern (P=0.007, HR 1.4), aberrant CD11b/CD16 expression pat - treatment weeks 5-12, fewer pts receiving EPAG experienced clinically relevant tern (P=0.003, HR 1.6), CD56 expression (P<0.001, HR 2.1), reduced CD33 thrombocytopenic events (plt counts <10 Gi/L, plt transfusions, or ≥Grade 3 hem - expression (P=0.018, HR 1.6) in granulocytes; CD56 expression (P<0.001, orrhagic events) per week than PLB (weighted average [range]: EPAG: 38% HR 1.6) in monocytes; reduced CD71 expression (P<0.001, HR 2.1) in erythroid [30%>48%]; PLB: 66% [56%>88%]). cells. A flow score was devised calculating for each pt the sum of all HRs for the respective parameters found positive. Pts were separated into 4 groups: group 1 (n=263 pts), score of 0; group 2 (n=259), score >0 and below the medi - Table 1. an (2.1); group 3 (n=149), score above the median and below the 75 th per - centile (5.0); group 4 (n=133), score above the 75 th percentile. 4-yr-OS in groups 1/2/3/4 was 82.4%/67.1%/54.7%/36.2%, respectively (P=0.001 1 vs 2, P=0.022 2 vs 3, P=0.003 3 vs 4, P<0.001 all other comparisons). Cox analysis of MFC score revealed a significant association with OS (P<0.001, HR 1.4 per group). Other parameters univariately related to OS were: diagnosis of MDS by CM (P<0.001, HR 2.2),% bone marrow blasts by CM (P<0.001, HR 1.9 per 10% increment), cytogenetic IPSS-group (P<0.001, HR 5.1 per group), WBC count (P<0.001, HR 1.2 per 10 G/L increment), hemoglobin level (P<0.001, HR 0.8 per g/L), platelet count (P<0.001, HR 1.4 per 100 G/L increment), and age (P<0.001, HR 1.5 per decade). Multivariate Cox analysis including flow score and established diagnostic markers as covariates revealed an independent impact on OS for all of them: flow score (P<0.001, HR 1.3), diagnosis of MDS by CM (P=0.003, HR 1.4), bone marrow blasts by CM (P=0.015, HR 1.4), and cytogenetics (P<0.001, HR 2.9). The flow score was still indenpendently relat - ed to OS when age and peripheral blood counts were included as covariates. The second set of analyses was performed in subgroups of patients accord - ing to results of CM. In cases with MDS proven by CM flow score was confirmed independently associated with OS (P=0.001, HR 1.2). Interestingly, even in cas - es with signs of dysplasia by CM, which are not sufficient to diagnose MDS, the 4 groups derived from the flow score differed significantly in OS (2-year- OS 85.9%/76.4%/73.0%/62.9%, P=0.024), Furthermore, multivariate analysis confirmed the independent impact of the flow score on OS (P=0.016, HR 1.3) within this cohort. Summary and Conclusions: MDS-related findings by MFC in MDS provide prognostic information not just in pts with MDS proven by CM but also in a com - prehensive cohort of pts being diagnosed for suspected MDS. Furthermore, even in pts with evidence of dysplasia not sufficient to diagnose MDS by CM a prognostic impact of MFC was demonstrated. This data thus suggests to integrate MFC into the diagnostic work-up of pts with suspected MDS.

S1110 ELTROMBOPAG FOR THE TREATMENT OF THROMBOCYTOPENIA OF LOW AND INTERMEDIATE-1 IPSS RISK MYELODYSPLASTIC SYN - DROMES: RESULTS OF A PROSPECTIVE, RANDOMIZED, TRIAL E Oliva 1,* , V Santini 2, G Zini 3, G Palumbo 4, A Poloni 5, A Cortelezzi 6, F Rodeghiero 7, M Voso 8, A Molteni 9, G Sanpaolo 10 , A Liberati 11 , F Morabito 12 , 13 14 15 16 1 1 17 Summary and Conclusions: EPAG ≤300mg was well tolerated in pts with E Balleari , S Impera , F Salvi , M Spiriti , A Marino , F Rodà , C Alati , F Ronco 1, F Raimondo 14 , P Leoni 18 , G Alimena 19 , G Fioritoni 20 , R Latagliata 21 , advanced MDS or AML. Pts treated with EPAG showed a trend toward fewer 1 plt transfusions, fewer ≥Grade 3 hemorrhages, and improved OS compared F Nobile 1Hematology, A.O. Bianchi-Melacrino-Morelli, Reggio Calabria, 2Hematology, with PLB. Additional studies with EPAG to evaluate potential antileukemic activ - 3 ity in advanced MDS or AML are warranted. A.O. Universitaria Careggi, Firenze, Struttura Complessa di Emotrasfusione, Policlinico Agostino Gemelli, Roma, 4Hematology, Ospedale Ferrarotto, Cata - nia, 5Hematology, Ospedale Riuniti, Ancona, 6Hematology, IRCCS Ospedale 7 S1109 Maggiore Policlinico, Milano, Hematology, Ospedale San Bortolo, Vicenza, 8Hematology, Policlinico Gemelli, Roma, 9Hematology, Ospedale Niguarda, PROGNOSTIC VALUE OF DISTINCT ABERRANCIES IN ANTIGEN Milano, 10 Hematology, Ospedale Casa Sollievo della Sofferenza, San Giovan - EXPRESSION AS ASSESSED BY MULTIPARAMETER FLOW CYTOME - ni Rotondo, 11 Hematology, A.O. Santa Maria, Terni, 12 Hematology, Ospedale TRY IN PATIENTS WITH SUSPECTED MDS L’Annunziata, Cosenza, 13 Hematology, Università degli Studi di Genova, Gen - W Kern 1,* , C Haferlach 1, T Alpermann 1, S Schnittger 1, T Haferlach 1 ova, 14 Hematology, Ospedale Garibaldi, Catania, 15 Hematology, A.O. SS. 1MLL Munich Leukemia Laboratory, Munich, Germany Antonio e Biagio e Cesare Arrigo, Alessandria, 16 Hematology, Ospedale San - t’Andrea, Rome, 17 Hemaology, A.O. Bianchi-Melacrino-Morelli, Reggio Cal - Background: Multiparameter flow cytometry (MFC) is increasingly used to abria, 18 Hematology, Ospedali Riuniti, Ancona, 19 Hematology, Policlinico Uni - diagnose myelodysplastic syndromes (MDS). The prognostic impact of distinct versitario Umberto I, Roma, 20 Hematology, Ospedale Civile, Pescara, 21 Hema -

456 | haematologica | 2013; 98(s1) Stockholm, Sweden, June 13–16, 2013 tology, Policlinico Universitario Umberto I, Rome, Italy these pts ongoing in the extension phase. Primary reasons for study discontin - Background: Low and Int-1 International Prognostic Scoring System (IPSS) uation were AEs (16.4%) and disease progression (15.1%) in the ruxolitinib arm risk MDS patients may experience severe thrombocytopenia associated with and withdrawal of consent and other (12.3% each) with BAT. The median dura - risk of hemorrhage. Eltrombopag is an oral agonist of the thrombopoetin-recep - tion of exposure was 136 wk to ruxolitinib (randomized and extension phases) tor (TPO-R) indicated for treating chronic immune thrombocytopenic purpura. and 45 wk to BAT (randomized treatment only). Overall, 75 pts (51.4%) treat - Eltrombopag’s potential in increasing PLT counts in lower risk MDS has not ed with ruxolitinib achieved a ≥35% reduction from baseline in spleen volume, been evaluated. We present interim results of a Phase II, multicentre, prospec - and 6 of these pts achieved a ≥35% reduction after the primary analysis at 48 tive, placebo-controlled, single-blind study (EQoL-MDS). wk. Reductions in spleen volumes were sustained with continued ruxolitinib Aims: Primary endpoints are safety and efficacy of eltrombopag in low and therapy (median duration not yet reached; Figure 1). Overall, 51 patients died: intermediate-1 IPSS risk. Secondary endpoints include changes in quality of life 29 (19.9%) in ruxolitinib arm and 22 (30.1%) in BAT arm; there was a 52% (QoL), PLT transfusion requirement, incidence and severity of bleeding, and reduction in risk of death in the ruxolitinib arm compared with BAT (HR=0.48; survival. 95% CI, 0.28-0.85; log-rank P=.009 [unadjusted for multiple comparisons]; Fig - Methods: Adult patients (N=171) are being included if: PLT<30 Gi/L; ECOG ure 2). The estimated probability of being alive at 144 wk was 81% in ruxoli - performance status <4; ineligible for, relapsed or refractory to other treatments; tinib arm and 61% in BAT arm. With longer treatment duration (median expo - and naive to TPO-R agonists. Eltrombopag/placebo (2:1) will be administered sure: ruxolitinib, 136 wk; BAT, 45 wk), there were no newly reported or unex - at a 50 mg daily starting dose with 50 mg increases every 2 weeks to maximum pected AEs among those that were most common. Consistent with ruxolitinib’s 300 mg to target PLT 100 Gi/L. Dose interruptions or reductions are required mechanism of action and previous reports, the most common AEs were ane - for PLT >200 Gi/L or adverse events. PLT response is defined as Response (R) if: 1) baseline PLT>20 Gi/L: absence of bleeding and PLT≥50Gi/L; 2) base - mia (ruxolitinib, 50.0%; BAT, 16.4%) and thrombocytopenia (50.7%; 13.7%). line PLT<20 Gi/L: PLT>20 Gi/L and increase by at least 100%, not due to PLT The most common non-hematologic AEs were peripheral edema (ruxolitinib, transfusions; and Complete Response (CR) if PLT≥100 Gi/L and absence of 36.3%; BAT, 28.8%), diarrhea (32.2%; 17.8%), asthenia (24.0%; 12.3%), dys - bleeding. Peripheral and bone marrow blood morphology (centralized and blind) pnea (23.3%; 20.5%), pyrexia (24.0%; 9.5%) and fatigue (23.3%; 11.0%). Five and cytogenetics are performed throughout the study. QoL scores are evalu - (3.5%) pts and 4 (5.5%) pts developed leukemia in the ruxolitinib and BAT ated by EORTC QLQ-C30 and QOL-E instruments. arms, respectively. Results: Thirty-one patients (21 on eltrombopag–Arm A), have been random - ized and 5 are in screening at the time of this report. Mean age is 66 (SD 12) years, male/female 18/13. Baseline mean PLT count was 16 (SD 8) Gi/L. Three cases in Arm A and 1 in Arm B had significant bleeding requiring PLT transfu - sions. Fifteen patients have reached a 12-week follow-up: 12 out of 15 cases in Arm A have obtained PLT responses at median 100 mg dosing associated with disappearance of bleeding and PLT transfusion independence. There were no responses in Arm B. At 12 weeks, PLT count increased from baseline by mean 64 (SD 77) Gi/L (P=0.006) in Arm A versus no significative changes in Arm B. Fatigue and general QoL improved significantly from baseline in Arm A. Grade III-IV unrelated adverse events occurred in 4 patients in Arm A (infec - tious complications, arthritis, heart diseae). Bone marrow blasts reduced in 3 cases during treatment in Arm A, versus 2 progressions in Arm B. Summary and Conclusions: Preliminary results in low and Intermediate-1 risk IPSS MDS patients with thrombocytopenia suggest safety and efficacy of eltrombopag in terms of response rates and improvements in quality of life. Figure 1. Kaplan-Meier analysis of maintenance of spleen response with Ruxolitinib treatment. S1111 LONG-TERM OUTCOMES FROM A PHASE 3 STUDY COMPARING RUX - OLITINIB WITH BEST AVAILABLE THERAPY (BAT) FOR THE TREAT - MENT OF MYELOFIBROSIS (MF): A 3-YEAR UPDATE OF COMFORT-II A Vannucchi 1,* , F Cervantes 2, D Niederwieser 3, A Sirulnik 4, V Stalbovskaya 5, M McQuitty 6, R Levy 7, F Passamonti 8, T Barbui 9, H Gisslinger 10 , L Knoops 11 , C Harrison 12 , G Barosi 13 , J Kiladjian 14 1University of Florence, Florence, Italy, 2Hospital Clínic, IDIBAPS, Barcelona, Spain, 3University of Leipzig, Leipzig, Germany, 4Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States, 5Novartis Pharma AG, Basel, Switzerland, 65Novartis Pharmaceuticals Corporation, East Hanover, NJ, 7Incyte Corporation, Wilmington, DE, United States, 8Ospedale di Circolo e Fondazione Macchi, Varese, 9A.O. Ospedali Riuniti di Bergamo, Bergamo, Italy, 10 Medical University of Vienna, Vienna, Austria, 11 Cliniques Universi - taires Saint-Luc and de Duve Institute, Université catholique de Louvain, Brus - Figure 2. Kaplan-Meier analysis of overall survival. sels, Belgium, 12 Guy’s and St. Thomas’ NHS Foundation Trust, London, Unit - ed Kingdom, 13 IRCCS Policlinico San Matteo Foundation, Pavia, Italy, 14 Hôpi - tal Saint-Louis et Université Paris Diderot, Paris, France Summary and Conclusions: This long-term analysis shows that ruxolitinib continues to be well tolerated and provides rapid and durable reductions in Background: Ruxolitinib is a potent JAK1/JAK2 inhibitor that has demonstrat - splenomegaly that are sustained for ≥3 years of treatment. Ruxolitinib-treated ed rapid and durable improvements in splenomegaly, MF-related symptoms and patients showed a longer survival over those receiving BAT, consistent with the quality of life in the 2 phase 3 COMFORT studies. COMFORT-II is a random - survival advantage observed in previous analyses of COMFORT-II (Cervantes ized, open-label study comparing ruxolitinib with BAT in patients (pts) with MF. et al. Blood. 2013 ) and COMFORT-I (Verstovsek et al. NEJM. 2012). Two-year follow-up of COMFORT-II confirmed that spleen volume reductions were sustained and ruxolitinib treatment remained tolerable with long-term use. This 3-year follow-up presents longer-term survival data and updates the long- term efficacy and safety findings of COMFORT-II. Aims: To update the efficacy and safety findings of COMFORT-II with 3 years of follow-up (cutoff date: 01 Dec 2012). Methods: Patients (n=219) with intermediate-2 or high-risk MF were random - ized (2:1) to receive ruxolitinib (15 or 20 mg bid, based on baseline platelet count [100-200 or >200×10 9/L, respectively]), or BAT. Efficacy results are based on an intention-to-treat analysis. A spleen response was defined as a reduction ≥35% from baseline in spleen volume; a loss of response was defined as a spleen volume increase >25% over on-study nadir that was no longer a ≥35% reduction from baseline. Overall survival was estimated using the Kaplan-Meier (KM) method. Results: After 3 years (median follow-up, 151 wk), 45.2% of patients in the rux - olitinib arm remain on treatment. All patients randomized to BAT discontinued treatment: 45 pts (61.6%) crossed over to receive ruxolitinib with 22 (48.9%) of

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