ALBERT

Description: Background: Understanding health-related quality of life (HRQOL) profile, including functional aspects and symptom burden, of yet untreated patients with myelodysplastic syndromes (MDS) is important to help clinicians to better identify subgroup of patients in need of special attention from the very beginning of therapy. Aims: The primary objective of this study was to investigate baseline (i.e., pretreatment) HRQOL profile of untreated patients with lower-risk MDS, examining differences by age, gender, risk score category and comorbidity. A secondary objective was to provide age and sex baseline reference HRQOL values, according to the EORTC QLQ-C30 questionnaire, to be used as benchmark comparisons in future MDS studies. Methods: This analysis is based on 443 newly diagnosed adult MDS patients with International Prognostic Scoring System (IPSS) risk score of low (46 %) or intermediate-1 (54%), enrolled in an international prospective cohort observational study. Median age was 75 years (range 32-94), with 261 men (59%) and 182 (41%) women. HRQOL was assessed by the EORTC QLQ-C30 questionnaire at study entry, before any treatment (except for transfusions). This well validated questionnaire consists of five functioning scales: physical, role, emotional, cognitive and social; three symptom scales: fatigue, nausea/ vomiting and pain; six single item scales: dyspnoea, sleep disturbance, appetite loss, constipation, diarrhea and financial impact; and the global health status/HRQOL scale. The items were scaled and scored using the recommended EORTC procedures. At the time of baseline HRQOL assessment, 111 (25%) patients had received at least one red blood cell transfusion. We used Wilcoxon-Mann-Whitney and Kruskal-Wallis tests for all comparisons. We used the false discovery rate approach to account for multiple testing, with a nominal α-level=0.05. In addition to statistical significance, clinically relevant HRQOL differences were also evaluated based on previously published criteria (Cocks K, et al, J Clin Oncol 29:89-96, 2011). Results: There were not statistically significant differences in any of the HRQOL scales measured by the EORTC QLQ-C30, by the specific IPSS risk category (i.e., low risk vs intermediate-1 risk score). Overall, women reported worse HRQOL scores than men, with clinically relevant differences for physical (Δ=-7.1, P=0.002), role (Δ=-9.9, P=0.002) and emotional functioning, (Δ=-10, P

Description: In vitro evidences suggest that bisphosponates (BP) may exert some anti-myeloma activities. Indeed, the use of BP has been associated with better survival in selected subgroups of myeloma patients. We have previously reported that pamidronate, a second generation BP, is not useful to prevent or to delay the need of chemo-radiotherapy in patients with early stage or smouldering myeloma, who do not require specific treatments at diagnosis, although such a therapy may reduce skeletal events at the time of disease progression (Musto et al, Leuk Lymphoma2003; 44: 1545). Based on this limited evidence, the recently updated ASCO guidelines still not recommend the use of BP in this specific setting of patients (Kyle et al, J Clin Oncol2007; 25: 2464). On June, 2001, we started a randomised clinical trial comparing zoledronate (ZOL), a third generation, more potent BP, vs simple observation in patients with monoclonal gammopathy fulfilling the diagnostic criteria of stage IA, IIA or smouldering myeloma, not requiring further treatments. These criteria substantially correspond to the current definition of “asymptomatic myeloma”, recently suggested by the International Myeloma Working Group (IMWG, Br J Haematol2003; 121: 749). Accrual was completed on June, 2004. One-hundred-sixty patients were enrolled and randomised (1:1) to receive (n. 80) or not (n. 80) ZOL (Zometa, Novartis Pharmaceuticals. Origgio, Italy) for one year, on an out-patient basis, at the dose of 4 mg as 15′ i.v. single monthly infusion. The two groups were comparable at baseline for time from diagnosis, levels and type of M-component and percentage of bone marrow plasma cells. The most frequent adverse effects observed in ZOL-treated patients were moderate, not clinically relevant hypocalcemia (15 patients: all received oral substitutive therapy and continued the treatment) and fever (7 patients, one of whom stopped drug administration after two cycles). One patient developed reversible osteonecrosis of the jaw, none evidenced renal failure under ZOL therapy. Eight patients (two in the ZOL-treated group and six within controls) died due to unrelated reasons or were lost at follow-up after 6–26 months. No significant reduction of M-component (〉 25%) was observed throughout the study in both groups. After a median follow-up of 55 months (range 36–72), there were 35 (46%) progressions to “symptomatic” myeloma in the ZOL group and 37 (50%) within the controls (p n.s.). Median time-to-progression was 42.2 and 40.7 months, respectively (p n.s.). Bone lesions and/or hypercalcemia at the time of progression were significantly lower (17/35, 48.5%) in ZOL-treated patients than in controls (30/37, 81%) (p 〈 0.02). These mature data suggest that the monthly use of ZOL for one year in patients with early-stage, asymptomatic myeloma is safe, reduces the development of skeletal events at progression, but does not decrease the number of evolutions and does not prolong the time to transformation into “overt” myeloma.

Description: Abstract 2864 Poster Board II-840 Background. New drug associations may improve patients outcome in relapsed/refractory multiple myeloma (MM). In newly diagnosed MM patients the addition of lenalidomide or thalidomide or bortezomib, to the standard oral melphalan and prednisone combination significantly increased response rate and event-free survival, showing synergistic effects. Aims. This is a multicenter, randomized, open label phase I/II trial designed to evaluate the safety/efficacy profile of the salvage treatment, Lenalidomide, Melphalan, Prednisone and Thalidomide (RMPT) in patients with relapsed/refractory myeloma. Methods. Oral lenalidomide was administered at 10 mg/day on days 1-21, in combination with oral melphalan at 0.18 mg/kg on days 1–4 and oral prednisone at 2 mg/kg on days 1–4. Thalidomide was administered at 50 mg/day (Arm A) or 100 mg/day (Arm B) on days 1-28. Each course was repeated every 28 days for a total of 6 courses. Maintenance therapy included Lenalidomide alone at 10 mg/day on days 1-21. Aspirin 100 mg/day was given as a prophylaxis for thrombosis. Results. Forthy-four patients with relapsed/refractory MM were enrolled in the study between May 2007 and March 2008, including 22 patients in arm A and 22 patients in arm B. After a median of 5 cycles 75% of patients achieved at least a partial response (PR), including 20% very good partial response (VGPR) and 14% near or complete response (nCR or CR). Among patients who received thalidomide 100 mg, the PR rate was 82% (including 23% VGPR and 23% CR/nCR). Higher response rate was observed among patients who received RMPT in first relapse. The 1-year-progression-free survival was 51,5% and the 1-year survival from study entry was 72%. Hematologic toxicity was the most frequent adverse event. Grade 3-4 hematologic adverse events included: neutropenia (68%), thrombocytopenia (36%) and anemia (32%). Grade 3-4 non hematologic adverse events included: infections (22,7%), neurological toxicity (4,5%) and fatigue (6,8%). No grade 3-4 thromboembolic events were reported. Conclusion. This is the first trial exploring the association of two immunomodulatory drugs, Thalidomide and Lenalidomide. RMPT is an active regimen in patients with relapsed/refractory MM. Toxicities were manageable and the incidence of neutrotoxcities was low. Updated results will be presented at the time of the meeting. Disclosures: Cavallo: CELGENE: Honoraria. Petrucci:CELGENE: Honoraria. Canepa:CELGENE: Honoraria. Boccadoro:CELGENE: CONSULTANCY, ADVISORY COMMITTEES, Research Funding. Palumbo:CELGENE: Honoraria.

Description: 5-Azacytidine (AZA) is an hypomethylating agent approved in US for the treatment of all FAB subtypes of myelodysplastic syndromes (MDS). Some recent reports have raised the question of a possible efficacy of AZA in selected patients with acute myeloid leukaemia (AML). In September 2007, we started a retrospective study aiming to register and analyse all Italian patients with MDS or AML who had received AZA for the treatment of their disease outside of clinical trials, on the basis of a national patient named program. Among a total of 246 patients treated in 31 different Italian Institutions since 2005, 55 AML diagnosed according to WHO criteria were collected. Median age was 72 years (range 29–87) and 28 patients were male. Poor karyotype was present in 11 patients (20%), while 14 patients (25%) had secondary AML. Median time from diagnosis was 5 months (range 0–72). Eighteen patients (33%) received AZA as front-line treatment, as they were considered not eligible for intensive chemotherapy due to age, co-morbidities or poor performance status. Thirty-seven patients (67%) were pre-treated with growth factors (3 patients) or with one or more lines of chemotherapy (11 and 23 patients, respectively); most of the pre-treated patients (22 out of 34) had received high dose chemotherapy, including autologous or allogeneic stem cell transplantation. Low dose chemotherapy had been employed in the remaining cases. The median number of monthly AZA cycles administered was 4 (range 1–22). Thirty-nine patients (71%) received AZA at the fixed dose of 100 mg/d s.c., 16 patients (29%) received a dose of 75 mg/sqm/d s.c.. A seven-day per month schedule was employed in 43 patients (78%), while 11 patients (20%) received AZA for more than 7 days and one patient for 5 days. Twenty-nine patients (52.8%) received AZA alone, twenty-six (47.2%) in various combinations with growth factors (1), valproic acid +/− ATRA (21) or gentuzumab-ozogamycin (4).The most relevant toxicities observed (grade 3–4) were represented by further myelosuppression (15%), infections (24%: in particular, 1 fungal lung infection, 3 pneumonia and 1 septic shock) and gastrointestinal adverse events (20%). The overall response rate was 35.3% (18/51): 8 patients achieved a complete remission (CR) (15.7%), while a partial response (PR) was observed in 5 patients (9.8%). Five haematological improvements were also seen (9.8%). Response rate was significantly higher in untreated patients compared to pre-treated ones (p=0.02). A statistically significant difference (p=0.04) in response rate in favour of 75 mg/sqm/d versus 100 mg fixed dose was also observed. The actuarial probability of overall survival (OS) at 16 months was 45% for patients responding to AZA and 10% for those non responding (p=0.0027). In conclusion, our data show that: AZA can induce significant responses in about one third of AML patients; the “standard” dose of 75 mg/sqm/d seems to be more effective than 100 mg/d (one single vial) fixed dose; AZA is more effective in de novo as compared to pre-treated (refractory and/or relapsed) disease; AML patients responding to AZA have a significant survival advantage compared to non responders.

Description: Background: In newly diagnosed multiple myeloma (MM) patients the addition of lenalidomide or thalidomide or bortezomib to the standard oral melphalan and prednisone (MP) combination significantly increased response rate and event-free survival. In advanced MM, the 4 drug combination VMPT further improves response rate. In this multicenter open label phase I/II trial the safety/efficacy profile of the 4 drug combination, lenalidomide, melphalan, prednisone and thalidomide (RMPT) was evaluated in patients with relapsed/refractory myeloma. Methods: Oral lenalidomide was administered at 10 mg/day on days 1–21, oral melphalan at 0.18 mg/kg on days 1–4, oral prednisone at 2 mg/kg on days 1–4. Thalidomide was administered at 50 mg/day (Arm A) or 100 mg/day (Arm B) on days 1–28. Each course was repeated every 28 days for a total of 6 courses. Aspirin 100 mg/day was given as a prophylaxis for thrombosis. Maintenance therapy included lenalidomide alone at 10 mg/day on days 1–21. Results: Forthy-four patients, median age 69 years (range 47–80), with relapsed or refractory MM were enrolled. Twenty-six patients received RMPT as second line of therapy, 18 as third line. Twenty patients received prior autologous transplant, 10 thalidomide-based regimen, 9 bortezomib-based regimen and 3 allogeneic stem cell transplant. After a median of 2 courses, 75.8% of patients achieved at least a partial response (PR), including 30% very good partial response (VGPR). Among patients who received RMPT as second line therapy the PR rate was 81.8%, including VGPR 36.4%.Among patients who received thalidomide 100 mg, the PR rate was 93.3% (including VGPR 46.7%) compared to 64.7% of thalidomide 50 mg. The 1-year-progressionfree survival was 48.6% and the 1-year survival from study entry was 90%. Grade 3–4 hematologic adverse events included: neutropenia (66.6%), thrombocytopenia (36.3%) and anemia (30.2%). Grade 3–4 non hematologic adverse events included: infections (21.2%), neurological toxicity (6%) and fatigue (9%). No thromboembolic events were reported. Conclusion: Initial results showed that RMPT is an effective salvage therapy with a high proportion of responses. Toxicities were manageable. No thromboembolic complications were reported.

Description: Abstract 2927 Background: Immunological changes have a primary role in the initiation and progression of myelodysplastic syndromes (MDS). Cytokine levels, such as IL-7 and IFN-gamma, are associated with lower-risk disease. Treatment with lenalidomide has proven efficacy in red blood cell (RBC) transfusion-dependent lower-risk MDS patients with del(5q). Lenalidomide exerts anti-angiogenic, anti-proliferative, and pro-erythropoietic effects; in particular, it has been shown that lenalidomide inhibits the proliferation and function of T regulatory cells (Tregs). Finally, MDS patients undergoing lenalidomide treatment experience erythroid responses and suppression of the del(5q) clone. Aims: In a multicenter Italian phase II trial to evaluate safety and efficacy of lenalidomide in primary MDS patients with del(5q) and Low- or Int-1 risk IPSS, we investigated changes in the transcription of cytokines and their receptors during treatment. Methods: The starting dose of lenalidomide was 10 mg p.o once daily on a continuous daily schedule for a maximum of 12 months. Bone marrow (BM) aspirates were obtained on study entry and every 12 weeks. Assays were performed using TaqMan® Low Density Array Fluidic card (TaqMan® Human Array, Applied Biosystems, Foster City, CA, USA) based on Applied Biosystems PRISM® 7900HT comparative ddCT method, according to the manufacturer's instructions. Target gene expression levels were measured in triplicate and normalized against the expression of the 18S housekeeping gene from a BM pool of normal, healthy subjects at all timepoints. Median relative gene expression values in MDS patients were compared to healthy subjects, set as a value of 1. Results: We report data obtained at baseline and after 12 weeks. Informed consent was obtained in all patients. Twenty-seven patients (5 M, 22 F) were evaluated at baseline and after 12 weeks. Mean age was 72 ± 9 years. Mean Hb level was 8.5 ± 0.9 g/dL and 16 patients were RBC transfusion -dependent (requiring at least 4 RBC transfusions in the preceding 2 months). Seven patients had additional cytogenetic abnormalities. Twenty-one patients (80%) experienced erythroid responses by week 12. Significant variations in gene expression of cytokines and receptors were observed during treatment. Genes significantly regulated during lenalidomide treatment (P 〈 0.05) are shown in the Table. In particular, FAS, IL-7 and FOXP3 gene were generally under-expressed at baseline and significantly increased after 12 weeks. Accordingly, IL7R was over-expressed in all patients at baseline and its expression was significantly reduced during treatment. Furthermore, IFN-gamma expression increased during therapy. Summary: The protein encoded by FAS gene is a member of the TNF-receptor superfamily and its interaction with its ligand leads to apoptosis. Interleukin (IL)-7 is an essential cytokine that promotes the proliferation and survival of B- and T-lymphocyte progenitors. The IL7R gene on chromosome 5 (5p13) codifies for the IL7 receptor, which blocks apoptosis during differentiation and activation of T lymphocytes. It functions, in part, through the induction of the expression of the antiapoptotic protein Bcl-2. The protein encoded by the FOXP3 gene is a member of transcriptional regulators. Defects in this gene are the cause of X-linked autoimmunity-immunodeficiency syndrome. The results of the present study indicate that lenalidomide may act through immunological changes. Further detailed analyses in these patients may provide new insights into the pathogenesis of MDS with del(5q) and the long-term effects of lenalidomide treatment on immunological changes in BM cells. Disclosures: Oliva: Celgene: Consultancy.

Description: Abstract 4953 Background: Shared decision-making between patients and physicians is broadly advocated in medicine, however little research is available to understand whether this approach would be desirable to all patients regardless of disease type and severity or individual patient characteristics. While clinical decision-making in high-risk myelodysplastic syndromes (MDS) is critical for a number of reasons including: associated comorbidity, symptom burden, and limited life expectancy, no evidence-base data currently exist on patients' preferences. Aim: The objective of this study is twofold: 1) to investigate to what extent high-risk MDS patients prefer to be involved in treatment decision making during consultation just after diagnosis; 2) to identify possible clinical, socio-demographic and patient-reported health status factors associated with patients' preferences for involvement in treatment decisions. Patients and Methods: Data were gathered through an ongoing international prospective observational study involving 15 countries that recruits newly diagnosed patients with intermediate-2 or high-risk IPSS score. All patients were classified according to the WHO histology classification. During the first encounter with their treating physicians, discussing treatment options just after diagnosis, patients were administered a previously internationally validated “control preference scale”. This scale broadly categorizes patients into one of three roles depending on the extent of their preferred involvement in treatment decision-making: “active” (where the patient themselves prefer to decide on which would be the most appropriate treatment option for themselves); “collaborative/shared” (where the patient and the doctor jointly decided on the most appropriate treatment option); “passive” (where the patient prefer to leave decision on the most appropriate treatment option to the doctor). Associations with the following variables were investigated: performance status, comorbidity (“Hematopoietic Cell Transplantation”-“Comorbidity index”), living arrangements, age, gender, education, cultural group, IPSS risk category, evolution from lower IPSS risk scores and patient-reported symptoms (using symptom scales of the EORTC QLQ-C30). Descriptive statistics were used and Mann-Whitney U-test, Kruskall-Wallis test and Fisher's exact test were used as appropriate to test statistical significance of performed comparisons. Results: Study population included overall 121 patients (38% female and 62% male). Mean age of patients was 69 years (min:31.3 max: 87.9) and 80% were diagnosed with IPSS int-2 risk score and 20% with IPSS high risk score. Twenty-six percent evolved from lower IPSS risk scores, while 74% were newly diagnosed with higher-risk. Forty-nine percent favored a passive while only 13% preferred an active role in treatment decision-making; the remaining 38% favored a collaborative/shared decision-making approach. Investigation of factors possibly related to preferred roles, found that passive role was significantly associated with lower education levels (P=.04). Among lower educated patients, 62.5% preferred a passive role compared with only 5% preferring an active role. When investigating relationships with patient-reported symptoms, a general trend for patients preferring a passive role, showing worse outcomes, was also evident. Higher symptom mean scores were found for passive vs. active role groups, being respectively: 46 (sd.26.6) vs. 37 (sd.29.9) for fatigue; 20 (sd.31.8) vs. 2 (sd.8.6) for constipation; 34 (sd.33) vs. 24 (sd.29.5) for dyspnea. Exploratory analysis showed that overall mean symptom score was statistically significant worse in patients preferring a passive role vs. those preferring an active role (P=.01). While other trends of associations were noted, these were not statistically significant. Conclusion: This is the first evidence suggesting that a consistent percentage of high-risk MDS patients prefer a passive role when discussing treatment options with their treating physicians at the time of diagnosis. There is also an indication that these patients are those with lower education levels and presenting with a higher symptom burden. Results need to be confirmed in a larger sample size. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 1949 Introduction: There is extensive evidence from numerous studies in the transplant setting that achievement of complete response (CR) or at least very good partial response (VGPR) is significantly associated with prolonged progression-free survival (PFS) and overall survival (OS). In elderly myeloma patients CR was a rare event since new drugs has been added to standard melphalan-prednisone (MP). After the introduction of novel agents, CR represents an achievable goal, also outside of the transplant setting. Aims: to assess the impact of response to treatment on time-to-event parameters (PFS and OS) in elderly myeloma patients. Methods: We retrospectively analysed newly diagnosed myeloma patients, older than 65 years old, or younger but not eligible for high-dose chemotherapy and transplant. Patients were enrolled in 3 multicentre randomized European trials of the GIMEMA and Hovon groups, and were treated with MP (n=332), MP plus thalidomide (MPT, n=332), MP plus bortezomib (VMP, n=257) or MP plus bortezomib-thalidomide followed by bortezomib-thalidomide maintenance (VMPT-VT, n=254). PFS, OS and duration of CR were analysed by the Cox proportional hazards model, comparing the two arms by the Wald test and calculating 95% confidence interval (CI). Univariate and multivariate analyses were performed for the following variables: age at diagnosis (〉75 vs. ≤75 yrs), International Staging System (ISS) stages, type of chemotherapy and best response achieved. Best response was treated as a time-dependent variable. Results: A total of 1,175 patients, enrolled from November, 2001 to January, 2009, were retrospectively analysed. The best response to treatment was available in 1,136 patients: CR was reported in 195, VGPR in 212, PR in 397. Baseline characteristics according to best response achieved in patients who obtained CR, VGPR or PR were similar. Since response rates vary according to treatment regimens the proportion of patients who received MP, MPT, VMP, and VMPT-VT was different in the different response categories. After a median follow-up of 29 months, PFS was significantly higher in patients who achieved CR compared to those who obtained VGPR (HR 0.16; 95% CI 0.10–0.24; p

Description: Abstract 3163 Background: Fatigue can potentially compromise activities of daily living and functional abilities in patients with myelodysplastic syndromes (MDS). These patients typically also have a limited life expectancy, thus making the improvement of health-related quality of life an important goal of therapy. However, there is paucity of evidence-based data in this area. Aims: To investigate the relationships between fatigue and physical, social and emotional functions in high-risk MDS patients and to evaluate socio-demographic and clinical characteristics associated with fatigue. Methods: Newly diagnosed patients with intermediate-2 or high-risk IPSS score are recruited in an international prospective observational study. Current analysis is based on patients recruited in 37 centers. A number of socio-demographic, clinical and laboratory variables were collected prior to treatment. Also, fatigue and functional abilities were measured before treatment start. Fatigue was evaluated with the FACIT-Fatigue scale. This is a simple 13-item psychometrically robust questionnaire that assesses self-reported tiredness, weakness and difficulty conducting usual activities due to fatigue. Functional abilities and quality of life (QoL) were assessed with the EORTC QLQ-C30. Both questionnaires have undergone rigorous linguistic cross-cultural validation and were available for all patients in the appropriate language. Functional aspects investigated included: physical (PF), role (RF), emotional (EF), cognitive (CF) and social functioning (SF). These scales range from 0 to 100, with higher scores representing better outcomes. Based on previous research, 10-points were considered to be a minimally important difference (MID) for the functional and QoL scales investigated. A score difference at least equal to MID was considered as a clinically meaningful difference. The cohort was divided into four groups based on the FACIT-Fatigue scores quartiles and patients were defined as having low, low/medium, medium/high and high fatigue levels. All variables investigated were summarized according to fatigue levels. Associations between fatigue levels and functional aspects, socio-demographic characteristics (i.e., age, gender, living arrangements, education) and clinical data (i.e., performance status and IPSS risk) were investigated using Chi-square and Kruskall-Wallis tests as appropriate. Multivariate stepwise regression analysis was also performed to investigate the impact of self-reported fatigue on functional scales. Results: Analysis is based on 240 patients, of whom 77% and 23% respectively classified with intermediate-2 and high-risk IPSS score. Median age of patients was 71 years (36% female and 64% male) and 49% had at least one comorbidity. Seventy-three percent of patients had an ECOG performance status ≥1. Patients with higher levels of fatigue reported worse scores in all functional aspects investigated. PF, RF and SF scales were found to be the most compromised aspects by fatigue severity. Mean score differences, between patients reporting low versus high fatigue levels were not only statistically significant (P

Description: Background: About 10% of low risk patients with myelodysplastic syndromes (MDS) experience severe thrombocytopenia. Bleeding and the scarce efficacy of platelet (PLT) transfusions drive research in novel treatments. Eltrombopag is an oral agonist of the thrombopoetin-receptor (TPO-R). Its potential in increasing platelet (PLT) counts in low risk MDS has not been evaluated. We present interim results on the efficacy and safety of eltrombopag in inducing PLT responses in patients with low and intermediate-1 International Prognostic Scoring System (IPSS) risk MDS with severe thrombocytopenia in a Phase II, multicentre, prospective, placebo-controlled, single-blind study (EQoL-MDS). Methods: Primary endpoints are safety and efficacy of eltrombopag. Secondary endpoints include changes in quality of life (QoL), PLT transfusion requirement, incidence and severity of bleeding, and survival. Inclusion criteria are adult age; PLT200 Gi/L or adverse events. Study design is shown in the figure. PLT response, assessed at each visit, is defined as Response if: 1) baseline PLT〉20 Gi/L: absence of bleeding and increase by at least 30 Gi/L from baseline; 2) baseline PLT20 Gi/L and increase by at least 100%, not due to PLT transfusions; and Complete Response if PLT≥100 Gi/L and absence of bleeding. QoL scores are analysed by MDS-specific instrument, QOL-E v. 3. Results: Seventy patients (46 on eltrombopag - Arm A, 24 on placebo -Arm B) have been randomized at the time of this report. Mean age is 68.3 (SD 13.0) years, M/F 38/32. ECOG performance status was 0 in 47 cases, 1 in 16 cases, 2 in 7 cases. Ten patients had comorbidities. According to the WHO 2008 classification, 22 patients had refractory cytopenia with unilineage dysplasia, 9 had refractory anemia with ringed sideroblasts, 31 had refractory cytopenia with multilineage dysplasia (of which 15 with ringed sideroblasts), 6 had refractory anemia with excess blasts-1 and 2 were unclassified. IPSS score was low in 48 cases. Mean baseline platelet (PLT) count was 17.1 (SD 8.2) Gi/L, mean hemoglobin level 10.8 (SD 2.5) g/dL and mean white blood cell count was 5.0 (SD 3.8) Gi/L. Twenty-five (36%) patients were red blood cell transfusion-dependent. Thirty-three had a WHO bleeding scale of 1, 2 experienced mild blood loss, 4 a gross blood loss and 1 a debilitating blood loss. Fourteen patients in Arm A and 8 in Arm B had required PLT transfusions in the 8 weeks prior to randomization. Twenty-three cases (50%) in Arm A have responded versus 2 (8%) in Arm B (p=0.001). Thirty-three patients have completed at least 24 weeks of study. Median time to response was 14 days (IQR 7-46 days) at a median daily dose of 75 (IQR 50-162.5 mg). PLT count increased by mean 53.2 (SD 68.1) Gi/L (p=0.001) in Arm A versus no significant changes in Arm B by week 24. QOL-E scores at baseline and 12 weeks in 47 cases in both arms are shown in the table. There was an increase in treatment outcome index,mainly experienced in the first 3 weeks (p=0.034). Fatigue improved from baseline to 12 weeks associated with response (p=0.016). Related Grade III-IV adverse events (AE) occurred in 10 patients (22%) in Arm A and consisted in: nausea (4), hypertransaminasemia (3), hyperbilirubinemia (1), sepsis (1), pruritis (1), heart failure (1), asthenia (1), vomit (1), while in Arm B 1 patient (4 %) experienced grade 3 bone marrow fibrosis. MDS disease progression occurred in 5 (11%) in Arm A versus 2 (8%) in Arm B, p=ns. Conclusions: Preliminary data indicate that lower risk MDS patients with severe thrombocytopenia undergoing treatment with eltrombopag experience significant improvements in PLT counts accompanied by improvements in fatigue. The drug appears to be well-tolerated and not associated with MDS progression. Further follow-up is required to evaluate the impact on survival. Figure 1. Study design Figure 1. Study design Figure 2. QOL-E domains at baseline and 12 weeks between Arm A (eltrombopag) and Arm B (placebo) Figure 2. QOL-E domains at baseline and 12 weeks between Arm A (eltrombopag) and Arm B (placebo) Disclosures Oliva: Novartis: Speakers Bureau; Celgene: Other: Advisory Board, Speakers Bureau; Amgen: Consultancy. Santini:celgene, Janssen, Novartis, Onconova: Honoraria, Research Funding. Palumbo:Novartis: Honoraria, Other: Advisory Board. Fenaux:Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene Corporation: Honoraria, Research Funding; Amgen: Honoraria, Research Funding.