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ß-thalassemia is a hereditary disorder with limited approved treatment options; patients experience anemia and its complications, including iron overload. The study aim was to determine whether luspatercept could improve anemia and disease complications in patients with ß-thalassemia. This open-label, nonrandomized, uncontrolled study consisted of a 24-week dose-finding and expansion stage (initial stage) and a 5-year extension stage, currently ongoing. Sixty-four patients were enrolled; 33 were non–transfusion dependent (mean hemoglobin, <10.0 g/dL; <4 red blood cell [RBC] units transfused per 8 weeks), and 31 were transfusion dependent (=4 RBC units per 8 weeks). Patients received 0.2 to 1.25 mg/kg luspatercept subcutaneously every 21 days for =5 cycles (dose-finding stage) and 0.8 to 1.25 mg/kg (expansion cohort and 5-year extension). The primary end point was erythroid response, defined as hemoglobin increase of =1.5 g/dL from baseline for =14 consecutive days (without RBC transfusions) for non–transfusion-dependent patients or RBC transfusion burden reduction =20% over a 12-week period vs the 12 weeks before treatment for transfusion-dependent patients. Eighteen non–transfusion-dependent patients (58%) receiving higher dose levels of luspatercept (0.6-1.25 mg/kg) achieved mean hemoglobin increase =1.5 g/dL over =14 days vs baseline. Twenty-six (81%) transfusion-dependent patients achieved =20% reduction in RBC transfusion burden. The most common grade 1 to 2 adverse events were bone pain, headache, and myalgia. As of the cutoff, 33 patients remain on study. In this study, a high percentage of ß-thalassemia patients receiving luspatercept had hemoglobin or transfusion burden improvements. These findings support a randomized clinical trial to assess efficacy and safety. This study was registered at www.clinicaltrials.gov as #NCT01749540 and #NCT02268409.

β-thalassemia is a hereditary disorder with limited approved treatment options; patients experience anemia and its complications, including iron overload. The study aim was to determine whether luspatercept could improve anemia and disease complications in patients with β-thalassemia. This open-label, nonrandomized, uncontrolled study consisted of a 24-week dose-finding and expansion stage (initial stage) and a 5-year extension stage, currently ongoing. Sixty-four patients were enrolled; 33 were non–transfusion dependent (mean hemoglobin, <10.0 g/dL; <4 red blood cell [RBC] units transfused per 8 weeks), and 31 were transfusion dependent (≥4 RBC units per 8 weeks). Patients received 0.2 to 1.25 mg/kg luspatercept subcutaneously every 21 days for ≥5 cycles (dose-finding stage) and 0.8 to 1.25 mg/kg (expansion cohort and 5-year extension). The primary end point was erythroid response, defined as hemoglobin increase of ≥1.5 g/dL from baseline for ≥14 consecutive days (without RBC transfusions) for non–transfusion-dependent patients or RBC transfusion burden reduction ≥20% over a 12-week period vs the 12 weeks before treatment for transfusion-dependent patients. Eighteen non–transfusion-dependent patients (58%) receiving higher dose levels of luspatercept (0.6-1.25 mg/kg) achieved mean hemoglobin increase ≥1.5 g/dL over ≥14 days vs baseline. Twenty-six (81%) transfusion-dependent patients achieved ≥20% reduction in RBC transfusion burden. The most common grade 1 to 2 adverse events were bone pain, headache, and myalgia. As of the cutoff, 33 patients remain on study. In this study, a high percentage of β-thalassemia patients receiving luspatercept had hemoglobin or transfusion burden improvements. These findings support a randomized clinical trial to assess efficacy and safety. This study was registered at www.clinicaltrials.govas #NCT01749540 and #NCT02268409.

Marasca: Roche: Honoraria; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria. Coscia:Karyopharm: Research Funding; ROCHE: Honoraria, Other: Advisory board; Janssen: Honoraria; Gilead: Honoraria; Mundipharma: Honoraria. Zinzani:Abbvie: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; MorphoSys: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Celegene: Membership on an entity's Board of Directors or advisory committees. Molica:Jansen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Roche Italy: Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Speakers Bureau. Orlandi:Ariad: Honoraria; BMS: Honoraria; Novartis: Honoraria. Ghia:Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Abbvie: Consultancy, Honoraria; Adaptive Biotechnology: Consultancy; Roche: Honoraria, Research Funding. Foà:Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; BMS: Consultancy; Genentech: Consultancy; Pfizer: Speakers Bureau; Ariad: Speakers Bureau.

Zhang: Acceleron Pharma: Employment. Wilson:Acceleron Pharma: Employment, Equity Ownership. Leneus:Acceleron Pharma: Employment. Laadem:Celgene Corporation: Employment, Equity Ownership. Sherman:Acceleron Pharma: Employment, Equity Ownership, Patents & Royalties. Attie:Acceleron Pharma: Employment, Equity Ownership.

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Piga: Celgene Corporation: Honoraria; Acceleron Pharma: Research Funding. Zhang:Acceleron: Employment. Bellevue:Acceleron: Employment. Wilson:Acceleron: Employment. Laadem:Celgene Corporation: Employment. Sherman:Acceleron Pharma: Employment. Attie:Acceleron: Employment.

Martinelli: Pfizer: Consultancy; Ariad: Consultancy; AMGEN: Consultancy; BMS: Consultancy, Speakers Bureau; ROCHE: Consultancy; MSD: Consultancy; Novartis: Consultancy, Speakers Bureau. Foà:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Introduction:Management of Ph+ ALL has changed since the introduction of tyrosine kinase inhibitors (TKI). We previously reported the preliminary findings of the GIMEMA LAL 1509 total therapy protocol, based on dasatinib plus steroids administration as induction therapy (Chiaretti et al, ASH 2014). The updated results on overall survival (OS), disease-free survival (DFS) and the impact of a genetic-based prognostic stratification are hereby provided.

Martinelli: Pfizer: Consultancy; BMS: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; ARIAD: Consultancy.

Piga: Acceleron Pharma: Research Funding; Celgene: Honoraria; Novartis: Research Funding; ApoPharma: Research Funding. Voskaridou:Celgene Coporation: Membership on an entity's Board of Directors or advisory committees. Condon:Acceleron Pharma: Employment, Equity Ownership. Wilson:Acceleron Pharma: Employment, Equity Ownership. Sherman:Acceleron Pharma: Employment, Equity Ownership. Attie:Acceleron Pharma: Employment, Equity Ownership.

Off Label Use: Bendamustine in diffuse large B-cell lymphoma. Zinzani:Genentech, inc.: Membership on an entity's Board of Directors or advisory committees.

The combination schedule of rituximab, fludarabine and cyclophosphamide is considered the standard therapy for fit and young untreated chronic lymphocytic leukemia (CLL) patients. However, although this therapy improves progression free survival (PFS) and overall survival (OS), it has been associated with increased toxicity: 76% of the patients experienced at least one grade 3 or 4 event. Recently, encouraging clinical results in terms of safety and efficacy have been obtained using bendamustine in combination with rituximab (R-B) in untreated CLL patients.

Prevalence of Left Ventricular Dysfunction (LVD), and Congestive Heart Failure (CHF) have been widely described in Thalassemia Major (TM) patients (pts), according to age, therapy, severity and coexisting diseases. However, so far no data are available in a large population adequately transfused and chelated. To determine the LV involvement in treated TM patients, we studied 524 pts from 5 Thalassemia Centers in Italy (49% males, mean age 30 yrs, range 16 to 56 yrs). In all pts clinical and echocardiographic data were recorded in WEBTHAL® database, a large co-operative Italian project among Thalassemia Centres based on an Internet-shared software for thalassemia. Data were evaluated blind by two independent researchers. Patients were considered having LVD if at least one cardioactive drug and/or history of cardiopathy (heart failure and/or clinically relevant arrhythmias) was recorded in their file (102/524 patients, 19,5%). Tables I and II summarize the echocardiographic results and cardiological treatment. Table I TM population without LV involvement (n°422 pts) and on cardiological treatment (n° 102 pts) Mean * Statistically significant between groups Pretrasfusional Hb (g/dl) 9,4 Ferritin (μg/dl) mean of last 10yrs 2027,7 LV end diastolic diameter index (mm/m2) 31,8 FS (%) 35,0 EF (%) 60,6 Duration of transfusion period (yrs) 24,5 Pretransfusional Hb (g/dl) 9,5 Ferritin (μg/dl) mean of last 10yrs * 2389,6 LV end diastolic diameter index (mm/m2)* 32,9 FS %* 31,3 EF % 54,4 Duration of transfusion period (yrs)* 26,2 Table 2 Cardiovascular Drugs N° % At least one drug 102 19,5 ACE Inhibitors 81 15,5 Diuretics 39 7,4 Beta-blockers 24 4,6 Antiarrhythmics 16 3,1 Digoxin 8 1,5 The majority of patients (422 subjects, 80.5%) did not take any cardioactive drugs and were considered without LV involvement. Systolic Pulmonary pressure was elevated (PH) (> 25 mmHg) in 10% of pts. ACE-inhibitors were the most used cardiovascular drug (15.5% of the pts), mainly males (n°56 pts, p<0.001). Pts on cardiological treatment showed lower FS%, compared to pts without cardioactive treatment (p< 0.001) and higher LV End Diastolic Diameter Index (32,9 vs 31,2, p< 0.009). Pts with LV involvement had a significatively longer regular trasfusional period compared to patients of matched age and they higher mean ferritin values (Tab1). Female patients had a significantly lower prevalence of LV involvement. In this group EF% and FS% were higher than in males (p< 0,001 and p<0,04, respectively). According to these data, LV involvement is characterized by a large and hypokinetic LV and occurs in 19% of a regularly transfused and chelated TM population. The LV disfunction is likely related to a long exposure to iron load in the heart. The mean values of clinical and echocardiographical variables of TM population without LV involvement can be considered as reference values (Table I).

Prevalence of Left Ventricular Dysfunction (LVD), and Congestive Heart Failure (CHF) have been widely described in Thalassemia Major (TM) patients (pts), according to age, therapy, severity and coexisting diseases. However, so far no data are available in a large population adequately transfused and chelated. To determine the LV involvement in treated TM patients, we studied 524 pts from 5 Thalassemia Centers in Italy (49% males, mean age 30 yrs, range 16 to 56 yrs). In all pts clinical and echocardiographic data were recorded in WEBTHAL® database, a large co-operative Italian project among Thalassemia Centres based on an Internet-shared software for thalassemia. Data were evaluated blind by two independent researchers. Patients were considered having LVD if at least one cardioactive drug and/or history of cardiopathy (heart failure and/or clinically relevant arrhythmias) was recorded in their file (102/524 patients, 19,5%). Tables I and II summarize the echocardiographic results and cardiological treatment.