ALBERT

Description: Background Cardiac iron removal is relatively slow and patients with cardiac siderosis can take years to normalize cardiac T2* to 〉20 ms. Prospective comparison of iron chelators are mostly limited to studies of 1-yr duration. CORDELIA is a large randomized trial comparing deferasirox (DFX) with deferoxamine (DFO) in patients with β-thalassemia major (TM), which demonstrated the non-inferiority of DFX vs DFO for cardiac iron removal at 1 yr, with a trend for superiority of DFX (P=0.057). This 1-yr extension was planned to collect additional data on efficacy and safety of DFX and DFO in patients with cardiac siderosis when treated for up to 2 yr. Methods Study design has been reported previously (Pennell Blood 2012; abst 2124). Patients enrolled had cardiovascular magnetic resonance-measured cardiac T2* 6–20 ms, left ventricular ejection fraction (LVEF) ≥56%, and R2-magnetic resonance imaging liver iron concentration (LIC) ≥3 mg Fe/g dw. Patients completing 1 yr were eligible to continue on DFX or DFO as assigned, or to switch treatment on entering the extension if judged by the investigator to be of therapeutic benefit. Target doses were an intensified DFO regimen of 50–60 mg/kg/d sc for 8–12 h, 5–7 d/wk, or DFX at 40 mg/kg/d. Efficacy is reported for changes from core baseline (BL). Safety was monitored continuously. Results for patients continuing with DFX or DFO are reported here. Results In total, 160/197 patients completed 1 yr; 74 patients continued into the extension on DFX (mean age 20.1 ± 6.9 yr; 59.5% male) and 29 patients on DFO (17.0 ± 5.4 yr; 58.6%). At core BL, 29.7% DFX patients had cardiac T2* 33% from BL and 〉 upper limit of normal (ULN) at 2 consecutive values occurred in 2.7% of DFX and 3.4% of DFO patients. Frequency of ALT elevations 〉5 x ULN and 2 x BL were comparable between groups. Discussion Cardiac T2* increased substantially during 2-yr treatment with DFX or DFO. Improvement with DFX was comparable with DFO, although DFO patient numbers were low. The magnitude of cardiac T2* improvement with DFX was consistent with previous long-term studies (Pennell Blood 2010). Mean LVEF was stable and remained within normal limits in both groups. LIC continued to decrease from very high BL levels with DFX and DFO. The reduction in CIC in the extension was similar or possibly greater than in the core, which might relate to the falling LIC. Long-term safety profiles of DFX and DFO were consistent with previous reports. Disclosures: Pennell: Shire: Consultancy, Honoraria; ApoPharma: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Porter:Celgene: Consultancy; Shire: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding. Piga:Novartis: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Wegener:Novartis: Employment. Habr:Novartis: Employment. Shen:Novartis: Employment. Aydinok:Shire: 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, Speakers Bureau.

Description: Background Transfusion-dependent patients with severe cardiac siderosis often require intensive iron chelation therapy for a limited time to facilitate rapid removal of iron from the heart, allowing patients to move from a high-risk (cardiac T2*

Description: Abstract 845 Background: Transfusion therapy can effectively treat many complications associated with sickle cell disease (SCD), but iron overload will develop without iron chelation therapy. Despite long-term transfusion requirements, long-term data for iron chelation in SCD are limited. The oral iron chelator, deferasirox, effectively reduced iron burden in SCD patients aged ≥2 years during 1 year of treatment (Vichinsky et al. Br J Haematol 2007). This 5-year follow-up is the first report of long-term deferasirox treatment in SCD patients. Methods: Eligible patients that completed the 1-year core study (randomized to deferasirox [deferasirox cohort] or deferoxamine [crossover cohort]) entered the 4- year extension. All received deferasirox while continuing their regular transfusion regimen. Deferasirox dose in the extension was initially based on serum ferritin (SF) trends in the core study (deferasirox cohort) or transfusion requirements (crossover cohort). Dose adjustments were based on monthly SF and safety assessments (investigator-reported adverse events [AEs] and centrally processed lab parameters). Growth and sexual development (Tanner staging) were assessed annually. Results: Of the patients in the deferasirox (n=132) and crossover (n=53) cohorts that received ’1 deferasirox dose during the core or extension, 43 (33%) and 19 (36%) patients, respectively, completed the extension. Reasons for discontinuation included withdrawal of consent (n=44, 23.8%), loss to follow-up (n=17, 9.2%) and AEs (n=14, 7.6%). Three deaths occurred, all in the extension (intraventricular hemorrhage, n=2; intracranial bleed post liver transplantation, n=1); none considered by investigators to be deferasirox-related. Mean dose during the study was 18.7 ± 6.5 and 21.2 ± 5.3 mg/kg/day in the deferasirox and crossover cohorts, respectively. Investigator-assessed drug-related AEs (≥5% overall) included nausea (14.6%), diarrhea (10.8%), increased blood creatinine (5.9%) and vomiting (5.4%). Generally, these AEs were manageable and transient, and decreased in frequency over time. Serious AEs were reported in 70.8% of patients overall and were mostly related to the underlying disease. Serious investigator-assessed drug-related AEs were reported in 8 patients (6.1%) in the deferasirox cohort and 1 patient (1.9%) in the crossover cohort. In the deferasirox and crossover cohorts respectively, 9 (6.8%) patients and 1 (1.9%) patient had 2 consecutive serum creatinine level increases 〉33% above baseline and 〉upper limit of normal (ULN). Median creatinine clearance remained stable within normal range throughout the study. One patient from each cohort had alanine aminotransferase (ALT) 〉10 × ULN on 2 consecutive visits; both had ALT values ≤ULN at the start of deferasirox treatment. In 37 patients with data available before and after dose increases to ≥30 mg/kg/day, no clinically relevant differences were observed in AE profile or laboratory parameters before and after dose increase. Deferasirox had no adverse effect on pediatric growth and adolescent sexual development. Overall, median SF levels in patients who received deferasirox treatment for ≥4 years decreased significantly from 3410 to 3108 ng/mL at end of study (median absolute change, –591 ng/mL, P=0.027; n=67). Decreases in SF were more pronounced when mean deferasirox dose increased to 〉20 mg/kg/day (Figure 1). In the deferasirox cohort, the median absolute change in SF levels from start of deferasirox to end-of-study was greater in patients aged ≥16 than 2–20 mg/kg/day, to achieve negative iron balance. Disclosures: Vichinsky: Novartis: Consultancy, Research Funding, Speakers Bureau; Apotex: Consultancy, Research Funding; Hemaquest: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bernaudin:Novartis: Investigator for SCD deferasirox (Exjade). Forni:Novartis: Research Funding. Gardner:Novartis: Research Funding. Hassell:Novartis: Research Funding. Heeney:Novartis: Research Funding. Kutlar:Novartis: Research Funding. Lane:Novartis: Research Funding. Mathias:Novartis: Research Funding. Porter:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Tebbi:Novartis: Speakers Bureau. Wilson:Novartis: Honoraria, Research Funding, Speakers Bureau. Griffel:Novartis: Employment. Deng:Novartis: Employment. Giannone:Novartis: Employment. Coates:Novartis: Research Funding, Speakers Bureau.

Description: Abstract 4272 Background: Globally, a number of management guidelines provide recommendations for transfusion and iron chelation therapy across various transfusion-dependent anemias. Most treatment guidelines aim to control body iron burden by maintaining serum ferritin 2500 ng/mL across all anemias. Serum ferritin levels were ≥2500 ng/mL in 61.3% of patients across regions (50.6% [Europe], 59.3% [Middle East/Africa] and 74.3% [Asia-Pacific]). For patients with TM, TI, AA and SCD, serum ferritin levels were substantially higher in the Asia-Pacific region compared with other regions (Figure). In the Asia-Pacific region, the proportion of patients with serum ferritin levels ≥4000 ng/mL varied between 31.1% and 53.6% across anemias, compared with 14.3–37.5% in Europe. Conclusions: There are many differences in transfusion and iron chelation practices across regions, with most prominent differences in the Asia-Pacific region. Factors contributing to these differences might include regional variations in specific disease characteristics (severity, transfusion requirement), treatment practices (eg, hemoglobin level at which transfusion is initiated), the availability and accessibility of transfusion and iron chelation therapy including patients' compliance and physician attitude and adherence to treatment guidelines. The high proportion of patients with baseline serum ferritin 〉2500 ng/mL suggests that previous iron chelation regimens with DFO and/or deferiprone prior to the EPIC study were suboptimal with limitations for adequate control of iron burden across geographical regions. A greater improvement in iron chelation practices is warranted across the globe with an immediate focus on the Asia-Pacific region. Disclosures: Viprakasit: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Gattermann:Novartis: Honoraria, Research Funding. Porter:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Taher:Novartis: Honoraria, Research Funding. Habr:Novartis: Employment. Roubert:Novartis: Employment. Domokos:Novartis: Employment. Cappellini:Novartis: Speakers Bureau.

Description: Hematopoietic stem cell (HSC) regulation is highly dependent on interactions with the marrow microenvironment. Controversy exists on N-cadherin's role in support of HSCs. Specifically, it is unknown whether microenvironmental N-cadherin is required for normal marrow microarchitecture and for hematopoiesis. To determine whether osteoblastic N-cadherin is required for HSC regulation, we used a genetic murine model in which deletion of Cdh2, the gene encoding N-cadherin, has been targeted to cells of the osteoblastic lineage. Targeted deletion of N-cadherin resulted in an age-dependent bone phenotype, ultimately characterized by decreased mineralized bone, but no difference in steady-state HSC numbers or function at any time tested, and normal recovery from myeloablative injury. Intermittent parathyroid hormone (PTH) treatment is well established as anabolic to bone and to increase marrow HSCs through microenvironmental interactions. Lack of osteoblastic N-cadherin did not block the bone anabolic or the HSC effects of PTH treatment. This report demonstrates that osteoblastic N-cadherin is not required for regulation of steady-state hematopoiesis, HSC response to myeloablation, or for rapid expansion of HSCs through intermittent treatment with PTH.

Description: Abstract 1869 BACKGROUND: The aggresome/autophagy pathway is the primary mechanism for disposal of ubiquitinated proteins for cells exposed to proteasome inhibition. Preclinical evidence shows that combining inhibition of the proteasome with bortezomib (Bz) and inhibition of autophagy with the anti-malarial drug hydroxychloroquine (HCQ) leads to enhanced cytotoxicity in myeloma cells. METHODS: Patients with relapsed or refractory myeloma enrolled on a standard 3+3 dose escalation design. Patients received 2-weeks of single-agent oral HCQ, followed by the addition of Bz on days 1, 4, 8, and 11 of 21-day cycles. HCQ and Bz doses were determined by dose level: (1) 200 mg qod / 1.0 mg/m2, (2) 200 qod / 1.3, (3) 200 qd / 1.3, (4) 200 bid / 1.3, (5) 400 bid / 1.3, (6) 600 bid / 1.3. Dose-limiting toxicity (DLT) was defined as grade ≥3 toxicity probably related to study therapy and occurring during the first 5 weeks, with the exception of any anemia or lymphopenia, neutropenia responsive to growth factor, platelets 〉10,000/mm3 not associated with bleeding, or gastrointestinal complaints relieved by symptomatic therapy. We used electron microscopy to characterize changes in autophagic vesicles in serial samples of peripheral blood mononuclear cells and CD138-selected bone marrow plasma cells. RESULTS: We enrolled 25 patients between 1/2008 and 2/2011, of which 21 patients completed at least 1 cycle of combined therapy and were evaluable for toxicity. The median duration of study participation was 14 weeks (range 1–77). Reasons for study discontinuation were side effects of therapy (6), lack of response (7), disease progression (11), and non-compliance (1). No protocol-defined dose limiting toxicities occurred, and the maximum tolerated dose was determined to be the top dose level of Bz 1.3 mg/m2 and HCQ 600 mg twice daily. Hematologic abnormalities were generally more attributable to disease progression than to treatment toxicity, but at the top dose level one patient had grade 3 thrombocytopenia and neutropenia after starting with a normal platelet count and ANC, without evidence of progression through therapy. At the top dose level, gastrointestinal toxicities predominated, including 5 out of 6 evaluable patients with some form of grade 3 GI toxicity. Treatment emergent neuropathy occurred in 7 patients but was restricted to grade 1 or 2 and was easily managed with dose reduction of the Velcade. Three patients came off study before receiving the combined regimen and were not evaluable for response. The best responses for the remaining 22 patients included 3 near complete responses (nCR), 3 minor responses (MR), 9 stable disease (SD), and 7 progression (PD). The 3 nCRs occurred in Bz-naïve patients receiving HCQ at 400 mg/d (1 pt) and 1200 mg/d (2 pts). Two patients who had previously progressed while receiving weekly maintenance Bz had MRs on study, including one who maintained a MR for over 7 months. Three additional Bz-refractory patients initially achieved stable disease during study treatment, with on study TTP of 8 weeks (at HCQ 1200 mg/d), 15 weeks (100 mg/d), and 17 weeks (200 mg/d). Preliminary analyses of vesicle counts at HCQ doses up to 800 mg/d identify individual patients with increases in autophagic vesicles in either peripheral blood or bone marrow plasma cells, but these are not consistent, nor is there any evident correlation with response. CONCLUSION: Combined Bz and HCQ is tolerable, with a phase 2 dose of Bz 1.3 mg/m2 and HCQ 1200 mg/d and likely hematologic and gastrointestinal DLTs. There is a suggestion of improved efficacy over Bz alone, with minor responses and long periods of stable disease in Bz-refractory patients. Final analysis of autophagy inhibition in correlative specimens, including the top dose cohort, will be available for the meeting. Disclosures: Vogl: Millennium Pharmaceuticals: Honoraria, Research Funding. Off Label Use: Hydroxychloroquine is FDA approved for treatment of malaria and rheumatoid arthritis. This paper discusses its use in treatment of myeloma. Carroll:Agios Pharmaceuticals: Research Funding; TetraLogic Pharmaceuticals: Research Funding; Sanofi Aventis Corporation: Research Funding; Glaxo Smith Kline, Inc.: Research Funding. Amaravadi:Millennium Pharmaceuticals: Honoraria, Research Funding.

Description: CTLO19 cells are CAR-modified T cells which recognize CD19 and produce high durable remission rates for pts with relapsed or refractory acute lymphoblastic leukemia (ALL). Cytokine Release Syndrome (CRS) has emerged as the major treatment related effect from CTL019, with symptoms that include high fevers and malaise but can progress to capillary leak, hypoxia and hypotension. CRS occurs hours to days after CTL019 infusion and correlates with rapid in vivo CTL019 expansion and marked elevation of serum IL6. In most cases, CRS is self-limited or rapidly reversed with anti-cytokine directed therapies. Here we report 3 cases of refractory CRS in adult pts with ALL. Our experience offers insight into clinical and investigational parameters describing this syndrome; highlights the variance of CRS across disease types and illustrates complexities of CRS management during concurrent infectious illness. As of 7/1/14, 97 pts (30 pediatric ALL, 12 adult ALL, 41 CLL, 14 NHL) have been treated with CTLO19. To capture clinical manifestations of CRS across protocols, we developed a novel CRS grading scale which will be described. Severe CRS (Gr 3-5) occurred in 27 (64%) of ALL pts and only 16 (29%) of CLL/NHL pts (p=0.001). 12 adults with ALL received CTL019; 8/9 evaluable pts achieved CR (MRD negative) at 1 month and 1 pt with extramedullary disease had marked reduction of PET avid disease which is maintained at 1 yr. Severe CRS occurred in 11 of 12 adult ALL pts. CRS was self-limited in 2 pts, rapidly reversed with anti-IL6 directed therapy in 6 pts and was refractory to therapy, contributing to death in 3 pts who were not evaluable for disease response. No baseline attributes differentiate these 3 pts from the 9 adult ALL pts with manageable Gr1-4 CRS. We have shown however that ALL disease burden correlates with CRS severity (in press) and all 3 pts had significant disease burden at baseline. All received lymphodepleting chemotherapy with cyclophosphamide 300 mg/m2 q12h x 6 followed by infusion of CTLO19 cells. These 3 pts each received 6.50E+06, 6.70E+06 and 8.45E+06 CTLO19 cells/kg compared to median CTL019 dose of 3.62E+06 in the 9 adult ALL pts with manageable CRS. Pt 21413-03 developed CRS 12 hrs after infusion and tested positive for influenza B on D3. Despite broad spectrum antimicrobials (including oseltamivir) and anticytokine directed therapy with tocilizumab (4mg/kg x 2) and steroids, he died with refractory hypotension on D5. Pt 21413-06 had extensive disease after 2 prior allogeneic SCTs and developed CRS within 12 hrs of infusion. In addition to broad spectrum antibiotics, she received tocilizumab 8mg/kg (D 3, 6 and 12); intermittent high dose steroids (D 4-15) and etanercept (D14). She died D15 with hypotension, hypoxic respiratory failure and concurrent MDR pseudomonas sepsis and pneumonia. Pt 21413-11 developed CRS within 24 hrs of infusion. He received tocilizumab 8mg/kg (D3&4); siltuximab (D5&15) and intermittent high dose steroids (D 4-15). After an initial response, he developed recurrent fever, pulmonary infiltrates and blood cultures positive for stenotrophomonas. He died D15 with refractory hypoxia and hypotension. All 3 pts’ clinical CRS correlated with marked in vivo CTL019 expansion and progressive serum cytokine elevations (data to be shown). CONCLUSIONS: CRS is the major toxicity of CTL019 therapy and its clinical course varies depending on disease type (more frequent and severe in ALL) and disease burden (in ALL). The 3 refractory CRS cases described here (of 97 total pts treated) have all occurred in adult ALL pts with significant disease burden who received relatively high doses of CTL019 cells. In addition, all 3 had significant infectious complications which potentially fueled underlying CRS and/or were made more virulent due to impairment of immunity with administration of anti-cytokine directed therapies. Future protocol modifications will be made goal of limiting severity of CRS while maintaining high durable remission rates. Further exploration is planned to better correlate timing and choice of anticytokine directed therapy in relation to clinical and investigation parameters of CRS. Disclosures Frey: Novartis: Research Funding. Off Label Use: USe of CART19 cells to treat CLL. Levine:Novartis: Patents & Royalties, Research Funding. Lacey:Novartis: Research Funding. Grupp:Novartis: Consultancy, Research Funding. Schuster:Novartis: Research Funding. Hwang:NVS: Research Funding. Leung:Novartis: Employment. Shen:Novartis: Employment. Ericson:Novartis: Employment. Melenhorst:Novartis: Research Funding. June:Novartis: Patents & Royalties, Research Funding. Porter:Novartis: Patents & Royalties, Research Funding.

Description: BACKGROUND: Effective and well tolerated treatment options for patients with relapsed acute myelogenous leukemia (AML) are limited. Birinapant is a small molecule, peptidomimetic of second mitochondrial-derived activator of caspases (SMAC) that selectively targets Inhibitor of Apotosis proteins (IAPs) resulting in tumor cell apoptosis and inactivation of NF-kB. SMAC mimetics represent a novel class of anti-tumor agents and birinapant has been explored as a single agent and in combination with chemotherapy in trials in solid tumors. Based on pre-clinical response observed in a mouse model with AML, we developed an investigator initiated Phase I clinical trial using single agent birinapant in pts with relapsed AML and high risk myelodysplastic syndrome (MDS). METHODS: Eligible pts were 〉18 years old with non-M3 relapsed or refractory AML or high risk MDS refractory to a hypomethylating agent. A standard 3+3 dose escalation was planned using single agent birinapant at increasing dose levels and frequency. Subjects who did not complete at least one cycle of therapy (4 wks) or experience a dose limiting toxicity (DLT) were replaced. The primary endpoint was safety and determination a maximum tolerated dose (MTD). Secondary endpoints included pharmacokinetic (PK) and pharmacodynamics (PD) analysis as well as disease response. RESULTS: From 12/2011 to 05/2014, 20 subjects were enrolled at the Hospital of the University of Pennsylvania and received at least one dose of study drug, 1 had MDS, 19 had AML (9 with antecedent MDS). The median age was 75 (range 36 to 80). The median number of prior treatments was 2 (range 1 to 5) and 11 patients required hydroxyurea during study treatment. No other concurrent chemotherapy was permitted. Several dose levels were tested varying the dose (17mg/m2, 22mg/m2 and 26mg/m2) and frequency (weekly, twice weekly (BIW) and 3 times weekly (TIW)) for 3 out of 4 wk cycles. Evaluable subjects have stayed on study drug for

Description: Abstract 5158 Objectives. Classic clinical and animal studies with deferoxamine (DFO) showed that two major chelatable pools exist in thalassemia major (TM), the first derived from hepatocytes and the second from red cell catabolism. Knowledge about the origin of chelatable iron with deferiprone (DFP) treatment, alone or when combined with DFO, is relatively limited. We hypothesized that changes in plasma iron species during chelation therapy may be proportional to the magnitude of chelatable iron pools. In this study, we have examined the relationship between urinary iron excretion (UIE), transfusional iron loading rates (ILR), liver iron concentration (LIC) and plasma concentrations of non-transferrin bound iron (NTBI) and labile plasma iron (LPI) before and after DFP therapies. Patients and methods. 12 TM patients were randomized to one year of DFP monotherapy (25mg/kg tds) or 9 to DFP at the same dose with the addition of subcutaneous DFO (40-50mg/kg), 2 nights a week (COMB). Plasma samples were taken for NTBI and LPI measurements, at baseline, at 1 week and at 52 weeks. These were obtained at 9am, which was 10hrs following the previous DFP dose, and 24h after the second of two weekly DFO doses for COMB patients. A 24h urine iron was collected at baseline, 1 week and 52 weeks of treatment. The ILR, expressed in mg/kg/day, was calculated from the blood volume transfused during the 1 year study. Results. After 1 week of treatment, there was a significant increase in NTBI from baseline in DFP and in COMB patients. A significant increase in LPI was also seen in DFP patients at this time (p=0.039). In all patients, absolute LPI levels at 1 week correlated with those of NTBI and increments in LPI also correlated with increments in NTBI from baseline to 1 week (r=0.52, p=0.002). Plasma NTBI levels at 1 week were proportional to UIE mg/kg/day)(r=0.51, p= 0.02), to LIC mg/g dry wt (r=0.54, p=0.01) and inversely proportional to the ILR (r=0.74, p=0.0001). By weighting the LIC and ILR pools equally, a combined chelatable pool index was derived: this was significantly proportional to both absolute NTBI at 1 week (r=0.72, p=0.003) and increments in NTBI from baseline. This index was also significantly correlated with UIE (p=0.66, p=0.0017) and with LPI at 1 week. Interpretation and conclusions. Urinary iron excretion with DFP (the predominant route of iron excretion with DFP) and COMB therapy is directly proportional to the LIC, as well as to plasma NTBI and LPI and is inversely proportional to the ILR. This is consistent with the existence of two major chelatable iron pools; the first being liver derived and the second derived from red cell catabolism. This latter pool appears to be larger for those patients who require less blood transfusion and who presumably have greater rates of ineffective eryrthropoiesis. The origin of chelatable iron with this form of COMB therapy, with DFO only two days a week, appears is similar to that of DFP monotherapy. Disclosures: Aydinok: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Off Label Use: Deferiprone and desferrioxamine are indicated and approved for the chelation therapy of iron-overloaded patients with beta thalassemia. The combination of both agents as treatment regimen for patients with beta thalassemia is part of the investigation described in the abstract and is not approved for use. Manz:Lipomed AG: Employment. Porter:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Description: Cardiac iron overload causes most deaths in β-thalassemia major. The efficacy of deferasirox in reducing or preventing cardiac iron overload was assessed in 192 patients with β-thalassemia in a 1-year prospective, multicenter study. The cardiac iron reduction arm (n = 114) included patients with magnetic resonance myocardial T2* from 5 to 20 ms (indicating cardiac siderosis), left ventricular ejection fraction (LVEF) of 56% or more, serum ferritin more than 2500 ng/mL, liver iron concentration more than 10 mg Fe/g dry weight, and more than 50 transfused blood units. The prevention arm (n = 78) included otherwise eligible patients whose myocardial T2* was 20 ms or more. The primary end point was the change in myocardial T2* at 1 year. In the cardiac iron reduction arm, the mean deferasirox dose was 32.6 mg/kg per day. Myocardial T2* (geometric mean ± coefficient of variation) improved from a baseline of 11.2 ms (± 40.5%) to 12.9 ms (± 49.5%) (+16%; P 〈 .001). LVEF (mean ± SD) was unchanged: 67.4 (± 5.7%) to 67.0 (± 6.0%) (−0.3%; P = .53). In the prevention arm, baseline myocardial T2* was unchanged from baseline of 32.0 ms (± 25.6%) to 32.5 ms (± 25.1%) (+2%; P = .57) and LVEF increased from baseline 67.7 (± 4.7%) to 69.6 (± 4.5%) (+1.8%; P 〈 .001). This prospective study shows that deferasirox is effective in removing and preventing myocardial iron accumulation. This study is registered at http://clinicaltrials.gov as NCT00171821.