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Background: Tisagenlecleucel is an autologous anti-CD19 chimeric antigen receptor (CAR)-T cell therapy that is approved for adult patients (pts) with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). In the phase 2 JULIET trial, pts could receive bridging therapy (BT), when needed, to permit flexibility in scheduling and maintain disease control. Lymphodepleting chemotherapy (LDC) was started 5-14 days prior to CAR-T cell infusion. Here we present baseline characteristics, efficacy/safety outcomes, and cellular kinetics by BT and type of LDC used in the JULIET trial. Methods: Pts were categorized based on BT or no BT, as well as LDC (cyclophosphamide/fludarabine [Cy/Flu; 250 and 25 mg/m2 IV daily for 3 doses, respectively] or bendamustine [90 mg/m2 IV daily for 2 days]) or no LDC, received prior to tisagenlecleucel infusion. Cy/Flu was the proposed regimen for LDC, followed by bendamustine (if the pt experienced previous grade [G] 4 hemorrhagic cystitis with Cy or demonstrated resistance to a previous Cy-containing regimen). LDC was not required if white blood cell count was Results: Of the 115 pts infused, 104 received BT (90 systemic therapy alone, 13 systemic therapy in combination with radiation therapy, and 1 radiation therapy alone) and 11 pts did not receive BT. For LDC, 85 pts received Cy/Flu, 22 bendamustine, and 8 pts did not receive LDC. Baseline and disease characteristics across the different BT and LDC categories are presented (Table). Of note, 90.9% (10/11) of pts who did not receive BT had baseline ECOG performance status 0, whereas 52.9% of pts who received BT had ECOG 0. Pts who did not receive BT had an ORR of 81.8% (63.6% complete response [CR]); in pts who received BT, the ORR was 49.0% (35.6% CR) (Table). Progression-free survival (PFS) rate at 12 months was 60.6% in pts who did not receive BT and 32.0% in pts who received BT. Among LDC groups, pts who received Cy/Flu had an ORR of 57.6% (41.2% CR) and 12-month PFS rate of 39.1%, whereas those who received bendamustine had an ORR of 40.9% (31.8% CR) and 12-month PFS rate of 21.2%. These differences were not statistically significant. Among pts who did not receive LDC, only 2/8 achieved a response (ORR 25% [25% CR]) and 12-month PFS rate was 25%. Rates of selected adverse events reported within ≤8 weeks post-infusion, >8 weeks to ≤1 year post-infusion, >1 year post-infusion, and any time after infusion were generally consistent across BT and LDC groups for prolonged cytopenias, neurological events (NE), cytokine release syndrome (CRS), and infection (Table). Of note, among pts who did not receive BT, only 1 G3 CRS and 1 G3 NE were reported, and no G4 CRS or NE were reported. Additionally, the rate of cytopenias not resolved by day 28 post-infusion was lowest among pts who did not receive BT (1/11 pts). However, cytopenias resolved to ≤G2 by month 3 or month 6 in the majority of pts. Cmax, Tmax, and exposure (AUC0-28d) were similar between LDC groups (Table). Cmax and AUC0-28d were also similar between pts who received BT and those who did not. Additional analyses of subgroups will be presented at the congress. Conclusions: The majority of pts enrolled in the JULIET trial received BT and LDC, indicating high tumor burden and aggressive disease in this pt population with r/r DLBCL. Although the sample size is small (n=11), pts not requiring BT appeared to have less aggressive disease, achieved high response rates, and had no G4 CRS or NE. Pts who did not receive LDC (n=8) seemed to have low response rates, suggesting either the impact of prior therapy, the importance of LDC, or both. Further evaluation of the impact of BT and LDC on clinical outcomes on larger patient population will be possible with the availability of registry data. Clinical trial information: NCT02445248 Table Disclosures Andreadis: Genentech: Consultancy, Employment; Merck: Research Funding; Roche: Equity Ownership; Novartis: Research Funding; Celgene: Research Funding; Juno: Research Funding; Pharmacyclics: Research Funding; Gilead: Consultancy; Kite: Consultancy; Jazz Pharmaceuticals: Consultancy. Tam:BeiGene: Honoraria; Roche: Honoraria; Novartis: Honoraria; Janssen: Honoraria, Research Funding; Pharmacyclics LLC, an AbbVie company: Honoraria; AbbVie: Honoraria, Research Funding. Borchmann:Novartis: Honoraria, Research Funding. Jaeger:Novartis, Roche, Sandoz: Consultancy; AbbVie, Celgene, Gilead, Novartis, Roche, Takeda Millennium: Research Funding; Amgen, AbbVie, Celgene, Eisai, Gilead, Janssen, Novartis, Roche, Takeda Millennium, MSD, BMS, Sanofi: Honoraria; Celgene, Roche, Janssen, Gilead, Novartis, MSD, AbbVie, Sanofi: Membership on an entity's Board of Directors or advisory committees. McGuirk:Astellas: Research Funding; Novartis: Research Funding; Fresenius Biotech: Research Funding; Gamida Cell: Research Funding; Pluristem Ltd: Research Funding; ArticulateScience LLC: Other: Assistance with manuscript preparation; Juno Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bellicum Pharmaceuticals: Research Funding. Holte:Novartis: Honoraria, Other: Advisory board. Waller:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Other: Travel expenses, Research Funding; Cerus Corporation: Other: Stock, Patents & Royalties; Chimerix: Other: Stock; Cambium Oncology: Patents & Royalties: Patents, royalties or other intellectual property ; Amgen: Consultancy; Kalytera: Consultancy. Jaglowski:Unum Therapeutics Inc.: Research Funding; Novartis: Consultancy, Other: advisory board, Research Funding; Juno: Consultancy, Other: advisory board; Kite: Consultancy, Other: advisory board, Research Funding. Bishop:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Juno: Consultancy, Membership on an entity's Board of Directors or advisory committees; CRISPR Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Foley:Celgene: Speakers Bureau; Amgen: Speakers Bureau; Janssen: Speakers Bureau. Westin:Curis: Other: Advisory Board, Research Funding; Janssen: Other: Advisory Board, Research Funding; Juno: Other: Advisory Board; Celgene: Other: Advisory Board, Research Funding; 47 Inc: Research Funding; Genentech: Other: Advisory Board, Research Funding; Novartis: Other: Advisory Board, Research Funding; MorphoSys: Other: Advisory Board; Unum: Research Funding; Kite: Other: Advisory Board, Research Funding. Fleury:Gilead: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; AstraZeneca: Consultancy. Ho:Novartis: Other: Trial Investigator meeting travel costs; La Jolla: Other: Trial Investigator meeting travel costs; Janssen: Other: Trial Investigator meeting travel costs; Celgene: Other: Trial Investigator meeting travel costs. Mielke:DGHO: Other: Travel support; IACH: Other: Travel support; EBMT/EHA: Other: Travel support; Miltenyi: Consultancy, Honoraria, Other: Travel and speakers fee (via institution), Speakers Bureau; GILEAD: Consultancy, Honoraria, Other: travel (via institution), Speakers Bureau; Jazz Pharma: Honoraria, Other: Travel support, Speakers Bureau; Kiadis Pharma: Consultancy, Honoraria, Other: Travel support (via institution), Speakers Bureau; Celgene: Honoraria, Other: Travel support (via institution), Speakers Bureau; ISCT: Other: Travel support; Bellicum: Consultancy, Honoraria, Other: Travel (via institution). Teshima:Novartis: Honoraria, Research Funding. Salles:Epizyme: Consultancy, Honoraria; Amgen: Honoraria, Other: Educational events; Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche, Janssen, Gilead, Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; BMS: Honoraria; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis, Servier, AbbVie, Karyopharm, Kite, MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events. Schuster:Novartis: Patents & Royalties: Combination Therapies of CAR and PD-1 Inhibitors (royalties to Novartis); i3Health, Dava Oncology, Novartis, OncLive, PER Oncology: Speakers Bureau; AbbVie, Acerta, Celgene, DTRM Bio, Genentech, Incyte, Merck, Novartis, Portola, TG therapeutics: Research Funding; AbbVie, Celgene, Novartis, Nordic Nanovector, Pfizer: Other: steering committee; Acerta, AstraZeneca, Celgene, Juno, LoxoOncology, Novartis: Other: advisory board; i3Health, Acerta, AstraZeneca, Celgene, Dava Oncology, Juno, LoxoOncology, Novartis, Nordic Nanovector, OncLive, PER Oncology, Pfizer: Honoraria. Bachanova:Kite: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding; Gamida Cell: Research Funding; GT Biopharma: Research Funding; Incyte: Research Funding; Celgene: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Maziarz:Novartis: Consultancy, Research Funding; Incyte: Consultancy, Honoraria; Celgene/Juno: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite: Membership on an entity's Board of Directors or advisory committees. Van Besien:Miltenyi Biotec: Research Funding. Izutsu:Eisai, Chugai, Zenyaku: Honoraria; Kyowa Kirin, Eisai, Takeda, MSD, Chugai, Nihon Medi-physics, Janssen, Ono, Abbvie, Dainihon Sumitomo, Bayer, Astra Zeneca, HUYA Japan, Novartis, Bristol-Byers Squibb, Mundi, Otsuka, Daiichi Sankyo, Astellas, Asahi Kasei: Honoraria; Celgene: Consultancy; Eisai, Symbio, Chugai, Zenyaku: Research Funding; Chugai, Celgene, Daiichi Sankyo, Astra Zeneca, Eisai, Symbio, Ono, Bayer, Solasia, Zenyaku, Incyte, Novartis, Sanofi, HUYA Bioscience, MSD, Astellas Amgen, Abbvie, ARIAD, Takeda, Pfizer: Research Funding. Wagner-Johnston:Gilead: Membership on an entity's Board of Directors or advisory committees; Jannsen: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees. Corradini:Amgen: Honoraria; Celgene: Honoraria, Other: Travel Costs; AbbVie: Consultancy, Honoraria, Other: Travel Costs; Daiichi Sankyo: Honoraria; Gilead: Honoraria, Other: Travel Costs; Janssen: Honoraria, Other: Travel Costs; Jazz Pharmaceutics: Honoraria; KiowaKirin: Honoraria; Kite: Honoraria; Novartis: Honoraria, Other: Travel Costs; Roche: Honoraria; Sanofi: Honoraria; Servier: Honoraria; Takeda: Honoraria, Other: Travel Costs; BMS: Other: Travel Costs. Tiwari:Novartis: Employment. Awasthi:Novartis: Employment. Lawniczek:Novartis: Employment. Eldjerou:Novartis Pharmaceuticals Corporation: Employment. Kersten:MSD: Other: Travel grants, honorarium, or advisory boards; Janssen/Cilag: Other: Travel grants, honorarium, or advisory boards; Kite: Consultancy, Other: Travel grants, honorarium, or advisory boards; Roche: Consultancy, Research Funding, Travel grants, honorarium, or advisory boards; Bristol Myers Squibb: Other: Travel grants, honorarium, or advisory boards; Takeda: Consultancy, Research Funding; Novartis: Consultancy, Other: Travel grants, honorarium, or advisory boards; Celgene: Other: Travel grants, honorarium, or advisory boards; Gilead: Other: Travel grants, honorarium, or advisory boards; Amgen: Other: Travel grants, honorarium, or advisory boards; Roche: Other: Travel grants, honorarium, or advisory boards; Celgene: Consultancy, Research Funding.

TPS7573 Background: Tisagenlecleucel is an anti-CD19 chimeric antigen receptor-T cell (CAR-T) therapy that was approved for the treatment of pediatric and young adult patients up to 25 years of age with r/r B-cell acute lymphoblastic leukemia in 2017 (Maude et al. NEJM. 2018), as well as for the treatment of adult patients with r/r diffuse large B-cell lymphoma in 2018 (Schuster et al. NEJM. 2018). FL is the second most common non-Hodgkin lymphoma in the Western hemisphere, with limited treatment options in patients refractory to or relapsing after standard therapies. In a phase 2a study of patients with r/r CD19+ lymphomas, 10 of 14 (71%) patients with r/r FL treated with tisagenlecleucel achieved a durable complete remission at a median follow-up of 28.6 months (Schuster et al. NEJM. 2017). Here we introduce ELARA, a phase 2 study evaluating the efficacy and safety of tisagenlecleucel in patients with r/r FL. Methods: ELARA is a phase 2, single-arm, multicenter, open label trial. Eligible patients must be ≥18 years of age, have radiographically measurable grade 1, 2, or 3A r/r FL that is refractory to a second or later line of systemic therapy (including an anti-CD20 antibody and an alkylator), or relapsed within 6 months after completion of a second or later line of systemic therapy, or relapsed during anti-CD20 antibody maintenance (following ≥2 lines of therapy as above) or within 6 months after maintenance completion, or relapsed after autologous hematopoietic stem cell transplant (HSCT). Patients with central nervous system involvement, or those who received prior anti-CD19 therapy, gene therapy, adoptive T-cell therapy, or allogeneic HSCT are not eligible. The primary endpoint of this study is complete response rate based on Lugano classification response criteria. Secondary outcomes include overall response rate, duration of response, overall survival, cellular kinetics, immunogenicity, safety, and patient-reported outcomes. Estimated enrollment for this study is 113 patients. The study is currently open to patient enrollment. Clinical trial information: NCT03568461.

Nontransfusion-dependent thalassemia (NTDT) patients may develop iron overload and its associated complications despite receiving only occasional or no transfusions. The present 1-year, randomized, double-blind, placebo-controlled THALASSA (Assessment of Exjade in Nontransfusion-Dependent Thalassemia) trial assessed the efficacy and safety of deferasirox in iron-overloaded NTDT patients. A total of 166 patients were randomized in a 2:1:2:1 ratio to starting doses of 5 or 10 mg/kg/d of deferasirox or placebo. The means ± SD of the actual deferasirox doses received over the duration of the study in the 5 and 10 mg/kg/d starting dose cohorts were 5.7 ± 1.4 and 11.5 ± 2.9 mg/kg/d, respectively. At 1 year, the liver iron concentration (LIC) decreased significantly compared with placebo (least-squares mean [LSM] ± SEM, −2.33 ± 0.7 mg Fe/g dry weight [dw], P = .001, and −4.18 ± 0.69 mg Fe/g dw, P < .001) for the 5 and 10 mg/kg/d deferasirox groups, respectively (baseline values [means ± SD], 13.11 ± 7.29 and 14.56 ± 7.92 mg Fe/g dw, respectively). Similarly, serum ferritin decreased significantly compared with placebo by LSM −235 and −337 ng/mL for the deferasirox 5 and 10 mg/kg/d groups, respectively (P < .001). In the placebo patients, LIC and serum ferritin increased from baseline by 0.38 mg Fe/g dw and 115 ng/mL (LSM), respectively. The most common drug-related adverse events were nausea (n = 11; 6.6%), rash (n = 8; 4.8%), and diarrhea (n = 6; 3.6%). This is the first randomized study showing that iron chelation with deferasirox significantly reduces iron overload in NTDT patients with a frequency of overall adverse events similar to placebo.

The highest approved dose of deferasirox is currently 30 mg/kg per d in many countries; however, some patients require escalation above 30 mg/kg per d to achieve their therapeutic goals. This retrospective analysis investigated the efficacy (based on change in serum ferritin levels) and safety of deferasirox >30 mg/kg per d in adult and paediatric patients with transfusion-dependent anaemias, including β-thalassaemia, sickle cell disease and the myelodysplastic syndromes. In total, 264 patients pooled from four clinical trials received doses of >30 mg/kg per d; median exposure to deferasirox >30 mg/kg per d was 36 weeks. In the overall population there was a statistically significant median decrease in serum ferritin of 440 μg/l (P 30 mg/kg per d was consistent with previously published data. There was no worsening of renal or liver function following dose escalation. Deferasirox >30 mg/kg per d effectively reduced iron burden to levels lower than those achieved prior to dose escalation in patients with transfusion-dependent anaemias. This has important implications for patients who are heavily transfused and may require higher doses to reduce body iron burden.

7026 Background: PV is a myeloproliferative neoplasm characterized by increased erythrocytosis, disease-related symptom burden (eg, pruritus), and risk of vascular events (thrombosis and/or hemorrh...

Background Polycythemia vera (PV) is the most common of the myeloproliferative neoplasms and is characterized by elevated hematocrit requiring phlebotomy, splenomegaly, a variety of symptoms and increased thrombotic risk. Ruxolitinib, a JAK1/JAK2 inhibitor, was well tolerated and achieved rapid and durable clinical responses in a phase 2 study of patients (pts) with PV who were resistant to or intolerant of hydroxyurea (HU). Pts experienced phlebotomy independence, resolution of splenomegaly, and improvements in white blood cell (WBC) counts, platelet (PLT) counts, and disease-related symptoms. Here, we describe the baseline (BL) characteristics and symptom burden of pts in a phase 3 study of ruxolitinib in pts with PV who are resistant to or intolerant of HU. Methods RESPONSE is a randomized (1:1), open-label, phase 3 study (NCT01243944) comparing the efficacy and safety of ruxolitinib with best available therapy (BAT) in pts with PV who are resistant to or intolerant of HU (modified European LeukemiaNet criteria), have splenomegaly, and require phlebotomy for inadequate hematocrit (Hct) control. Fourteen disease-related symptoms were assessed on a scale of 0 (absent) to 10 (worst imaginable) using the modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF). Blinded data are presented here. Results BL demographic data are available for the 222 enrolled pts (Table). Apart from HU, other common prior medications for PV included interferons (15%), PLT aggregation inhibitors (10%), alkylating agents (3.6%), alkyl sulfonates (3.2%), pyrimidine analogues (1.8%), and nitrosoureas (1.4%). The majority of pts (54.5%) had 1 phlebotomy within 12 weeks prior to screening; 23.9% had 2 and 17.1% had 3 or more phlebotomies. RESPONSE BL demographics are generally similar in terms of age (60 years vs 57-67); sex (66% male vs 58%-68%); Hct (44% vs 45%-48%); and platelets (419 x 109/L vs 320-429 x 109/L) to other PV studies including trials of givinostat (Finazzi BJH 2013) and AOP2014 (Gisslinger ASH 2012) and the ECLAP-PV (Marchioli JCO 2005) and CYTO-PV studies (Marchioli NEJM 2012). At the time of writing, BL symptom data from the MPN-SAF were available for 164 pts (Table). Pts in this study reported a similar symptom burden as PV pts from a large study of pts with MPNs (Emanuel JCO 2012; N = 1425; PV, n = 538), including similar mean scores for early satiety, abdominal discomfort, concentration problems, night sweats, itching, and tiredness/fatigue. In addition, prior therapy may have adversely affected BL symptom burden, as many of these symptoms (concentration problems, night sweats, fatigue) have been shown to be worsened by the use of conventional therapy to strictly control Hct (< 45%) and cardiovascular risk (Emanuel EHA 2013). BL MPN-SAF symptom data for all 222 pts will be presented. In addition, correlations between BL EORTC QLQ-C30 and MPN-SAF scores will be presented. Summary/Conclusions Demographic and BL symptom data from the RESPONSE study demonstrated that pts with HU refractory or intolerant PV have a significant disease burden that includes a variety of symptoms. These findings are consistent with those of Emanuel (JCO 2012), which showed that pts with PV have a significant symptom burden and a reduced quality of life. Pts with PV in the RESPONSE study are representative of those who have been studied in other clinical trials for the treatment of PV. Disclosures: Vannucchi: Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Off Label Use: Ruxolitinib, a JAK1/JAK2 inhibitor, has been approved by the US Food and Drug Administration for the treatment of intermediate- or high-risk MF and by the European Commission and Health Canada for the treatment of disease-related splenomegaly or symptoms in adult patients with MF. Here, we describe the baseline (BL) characteristics and symptom burden of patients in a phase 3 study of ruxolitinib in patients with PV who are resistant to or intolerant of HU. Kiladjian:Novartis: Honoraria; Shire: Honoraria. Durrant:Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Sanofi: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Pane:Novartis: Consultancy, Honoraria; Shire: Honoraria. Harrison:Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; YM Bioscience: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Celgene: Honoraria; Shire: Speakers Bureau; SBio: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity’s Board of Directors or advisory committees. He:Incyte: Employment. Leopold:Incyte: Employment, Stock options Other. Li:Novartis: Employment, Equity Ownership. Pirron:Novartis: Employment, Equity Ownership. Lawniczek:Novartis: Employment. Verstovsek:Incyte: Research Funding.

Abstract 3258 Background: Despite receiving occasional/no blood transfusions, non-transfusion-dependent thalassemia (NTDT) patients (eg β-thalassemia intermedia, mild/moderate HbE/β-thalassemia, α-thalassemia [HbH disease]) are at risk of iron overload, mainly due to increased intestinal iron absorption. The THALASSA 1-year randomized core study assessing deferasirox for investigational use in NTDT showed deferasirox superiority in reducing iron overload with a similar frequency of overall adverse events (AEs) compared with placebo (PBO). This 1-year extension evaluates continued efficacy/safety of deferasirox in patients receiving deferasirox in the core as well as patients receiving PBO who switched to deferasirox. Methods: Study design/inclusion-exclusion criteria have been described (Taher et al. Blood 2012). In the prospective, open-label, 1-year extension, patients whose LIC decreased ≥30% vs baseline (BL) continued at the same dose received at core end of study (EOS). Patients with LIC 3–15 or >15 mg Fe/g dw received deferasirox 10 or 20 mg/kg/day in the extension, respectively. After 6 months extension, patients with LIC 7 mg Fe/g dw at month 18 and with LIC reduction Results: 166 patients enrolled in the core study (deferasirox: 110; PBO: 56). 133/148 who completed the core entered the extension (deferasirox: 85; 48 PBO/DFX); 15 did not enrol in the extension (mainly due to extension amendment not approved when patients reached core EOS [n=8] and not interested in continuing [n=5]). 130 patients (84 [98.8%] deferasirox; 46 [95.8%] PBO/DFX) completed the extension; 1 patient discontinued in the deferasirox group (due to AE), 2 patients discontinued in the PBO/DFX group (due to AE [n=1], local admin problem [n=1]). Mean actual deferasirox dose was 9.8 ± 3.6 mg/kg/day (median 9.5) in core + extension; 12.6 ± 4.5 mg/kg/day (median 10.8) in the extension (n=82) and 13.7 ± 4.6 mg/kg/day (median 14.0) in patients who crossed over from PBO to deferasirox in the extension, notably higher than those continuing on deferasirox (Figure). Deferasirox group (core + extension n=110) Mean absolute change in LIC from BL to month 24 was –7.14 mg Fe/g dw (Figure). By EOS, 43 (39.1%), 18 (16.4%) and 80 (72.7%) patients achieved a LIC7 mg Fe/g dw, 51/92 (55.4%) achieved LIC ≤7 at EOS. Median change in serum ferritin from BL to EOS was –450 ng/mL. Most common AEs regardless of study drug relationship: upper respiratory tract infection (20.9%), pyrexia (17.3%), diarrhea (13.6%), headache and nausea (both 12.7%), upper abdominal pain, anemia and gastroenteritis (11.8%); serious AEs (>2%): gastroenteritis (6.4%), pyrexia (3.6%), anemia (2.7%). 5 (4.5%) patients had serum creatinine increases >33% above BL and above ULN at ≥2 consecutive visits. One patient had ALT increase >5 × ULN and >2 × BL. PBO/DFX group (core + extension n=56) 21 (37.5%), 6 (10.7%) and 36 (66.1%) patients achieved LIC7 mg Fe/g dw, 17/42 (40.5%) achieved LIC ≤7 at EOS. Patients who crossed over from PBO to deferasirox entered the extension with a higher extension BL LIC than those continuing on deferasirox. Most common AEs regardless of study drug relationship: pyrexia (26.8%), upper respiratory tract infection (25.0%), diarrhea, headache, nausea (21.4%), abdominal pain (16.1%), vomiting, cough (14.3%). Conclusions: In iron-overloaded NTDT patients treated with deferasirox in the core study, LIC continued to decrease in the extension with 39.1% and 16.4% of patients reaching LIC Disclosures: Taher: Novartis: Honoraria, Research Funding. Off Label Use: Exjade is indicated for the treatment of chronic iron overload due to frequent blood transfusions. This abstract describes off-label use of Exjade in patients with non-transfusion-dependent thalassemia syndromes with iron overload. Porter:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Viprakasit:GPO, Thailand: Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Kattamis:Novartis: Honoraria, Research Funding, Speakers Bureau. Chuncharunee:Novartis: Research Funding. Sutcharitchan:Novartis: Research Funding. Siritanaratkul:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Galanello:Ferrokin: Research Funding; Apopharma: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau. Karakas:Novartis: Honoraria. Lawniczek:Novartis: Employment. Habr:Novartis: Employment. Ros:Novartis: Employment. Zhu:Novartis: Employment. Cappellini:Novartis: Speakers Bureau.

Abstract 902 Background: Patients with thalassemic syndromes who require occasional or no blood transfusions are still at risk of iron overload (primarily from increased intestinal iron absorption caused by ineffective erythropoiesis) and associated serious complications. Iron chelation therapy (ICT) is the only option for decreasing iron burden, as phlebotomy is contraindicated due to anemia. The THALASSA 1-yr, randomized, double-blind, placebo-controlled study assessed efficacy and safety of deferasirox (DFX; Exjade®, once-daily oral iron chelator) in iron-overloaded patients with non-transfusion-dependent thalassemia (NTDT). Methods: NTDT patients aged ≥10 yrs with liver iron concentration (LIC) ≥5 mg Fe/g dry weight (dw) and serum ferritin (SF) >300 ng/mL were enrolled and randomized 2:1:2:1 to starting doses of DFX/placebo 5 mg/kg/day or DFX/placebo 10 mg/kg/day. Patient inclusion/exclusion criteria were reported previously (Taher et al. Blood 2009;114(22):abst 5111). DFX dose could be doubled at 24 wks in patients with insufficient response (LIC >7 mg Fe/g dw and reduction Results: 166 patients with β-thalassemia intermedia (n=95), α-thalassemia (n=22) or HbE/β-thalassemia (n=49) were randomized to starting DFX doses of 5 mg/kg/day (n=55) or matching placebo (n=28) and 10 mg/kg/day (n=55) or matching placebo (n=28). After 24 wks, 48.8% of all patients had a dose increase (47.3 and 45.5% in the DFX 5 and 10 mg/kg/day groups, respectively) resulting in an average actual dose (mean ± SD) of 5.6 ± 1.4 and 11.5 ± 2.9 mg/kg/day, respectively. At 1 year, LIC significantly decreased by –1.95 mg Fe/g dw (95% CI: –2.94, –0.96; BL: 13.11) and –3.80 mg Fe/g dw (95% CI: –4.76, –2.85; BL: 14.56) in the DFX 5 and 10 mg/kg/day groups, compared with an increase of 0.38 mg Fe/g dw (95% CI: –0.59, 1.34; BL: 15.94) in the placebo (Figure 1A); the difference between DFX 5 and 10 mg/kg/day groups vs placebo was significant (–2.33 mg Fe/g dw, P=0.001 and –4.18 mg Fe/g dw, P Mean serum ferritin significantly decreased at 1 yr: –121 ng/mL (95% CI: –203, –38) and –222 ng/mL (95% CI: –304, –140) for DFX 5 and 10 mg/kg/day groups (Figure 1B) while there was an increase in the placebo (115 ng/mL: 95% CI: 33, 196); difference vs placebo was significant (–235 ng/mL, P 148 (89.2%) patients completed 1 yr. In the placebo, DFX 5 and 10 mg/kg/day groups 8.9, 12.7 and 10.9% of patients discontinued, most commonly due to AEs (1.8, 3.6 and 5.5%, respectively). In addition, 1 patient (1.8%) in the placebo arm discontinued due to an abnormal lab value (low hemoglobin). Overall AE rates were 80.4, 76.4 and 78.2% in the placebo, DFX 5 and 10 mg/kg/day groups, respectively. The most common investigator-assessed drug-related AEs in the overall placebo (n=56), DFX 5 and 10 mg/kg/day groups, respectively, were nausea (7.1, 5.5 and 7.3%), rash (1.8, 3.6 and 9.1%), diarrhea (1.8, 0 and 9.1%), headache (3.6, 3.6 and 1.8%) and upper abdominal pain (0, 3.6 and 1.8%). Serious AEs were reported in 14.3, 12.7 and 16.4% of patients in the placebo, DFX 5 and 10 mg/kg/day groups, respectively. 3 (5.5%) DFX-treated patients (DFX 10 mg/kg/day) had 2 consecutive serum creatinine level increases >33% above BL and >upper limit of normal (ULN). 1 patient in the placebo group had an ALT increase >5 × ULN and >2 × BL and 2 patients had an AST increase to >5 × ULN and > 2 × BL, 1 in the DFX 10 mg/kg/day and 1 in the placebo group. Conclusions: This first randomized, placebo-controlled study evaluating ICT in NTDT patients confirms that these patients have high LIC despite moderately elevated SF, thus highlighting the need for ICT. Compared to placebo, 1-year DFX at starting doses of 5 and 10 mg/kg/day escalated to 10 and 20 mg/kg/day significantly reduced LIC and SF, along with a similar frequency of overall AEs. Disclosures: Taher: Novartis: Honoraria, Research Funding. Off Label Use: Exjade is indicated for the treatment of chronic iron overload due to frequent blood transfusions. This abstract describes off-label use of Exjade in patients with non-transfusion-dependent thalassemia syndromes with iron overload. Porter:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Viprakasit:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Kattamis:Novartis: Honoraria, Research Funding, Speakers Bureau. Chuncharunee:Novartis: Research Funding. Sutcharitchan:Novartis: Research Funding. Siritanaratkul:Novartis: Research Funding. Galanello:ApoPharma: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau. Karakas:Novartis: Honoraria. Lawniczek:Novartis: Employment. Ros:Novartis: Employment. Zhang:Novartis: Employment. Habr:Novartis: Employment. Cappellini:Novartis: Speakers Bureau.

Abstract 5111 Background Clinically mild forms of thalassemia exist that, unlike β-thalassemia major, require no or only infrequent transfusions (eg. β-thalassemia intermedia, HbH disease). However, due to increased gastrointestinal iron absorption secondary to ineffective erythropoiesis these patients may still develop iron overload. For example, thalassemia intermedia patients (n=74) within a cross-sectional study had a mean serum ferritin (SF) of 1023 ng/mL (range 15–4140) and a mean liver iron concentration (LIC) of 9 mg Fe/g dw (range 0.5–32.1) at baseline despite most being transfusion-naïve (n=20) or rarely transfused (n=45), and only nine receiving regular transfusions (2–4 times/yr) (Taher et al. ITIFPaP: 13th International TIF Conference for Thalassaemia Patients & Parents, October 8–11 2008, Singapore, poster number MON04). Non-transfusional iron overload leads to the same serious clinical sequelae as transfusional iron overload, including liver, cardiac and endocrine dysfunctions. As patients with non-transfusional iron overload are not candidates for phlebotomy due to their underlying anemia, chelation therapy is the only available option for decreasing their iron burden. However, there is currently limited data available on the use of chelation in this population. The once-daily oral iron chelator deferasirox (Exjade®) is currently approved for the treatment of iron overload in patients with transfusion-dependent anemia. This prospective, randomized, double-blind, placebo-controlled Phase II ‘THALASSA’ study will evaluate the efficacy and safety of deferasirox in patients with non-transfusion-dependent thalassemia. Methods Non-transfusion-dependent thalassemia patients aged ≥10 yrs will be randomized 2:1:2:1 to starting doses of deferasirox/placebo 5 mg/kg/day/ deferasirox/placebo 10 mg/kg/day over a planned 12-month treatment period. Doses can be doubled after 6 months should patients require a higher dose, which will be determined after 6 months of treatment. All patients are required to have a baseline LIC of ≥5 mg Fe/g dw, as measured by R2 magnetic resonance imaging, and SF levels of >300 ng/mL. Patients will be excluded if they have: anticipated regular transfusions during the study (sporadic transfusions, such as in cases of infection, are allowed); any transfusion within 6 months prior to study start, chelation within 1 month prior to study start; HbS variants of thalassemia; impaired renal and liver function. Primary efficacy endpoint is absolute change from baseline in LIC at 12 months; secondary efficacy endpoints include change from baseline in LIC after 6 months and in SF after 6 and 12 months, as well as change in hematological and iron metabolism parameters (eg hemoglobin, transferrin saturation). Safety assessments include adverse event and laboratory parameter monitoring. 156 patients are planned for inclusion. Results As of 3 August 2009, 18 sites had been activated. Sites currently activated are in Thailand (n=5), Turkey (n=4), Italy (n=3), Malaysia (n=2), UK (n=2) Lebanon (n=1). Fifty-seven patients have been randomized to either deferasirox or placebo and their demographic data are shown in Table 1. Conclusions Similar to transfusion-dependent thalassemia patients, non- transfusion-dependent thalassemia patients also develop iron overload. This ongoing study will generate prospective efficacy and safety data for the use of deferasirox in non-transfusion-dependent thalassemia patients with iron overload. To prevent long term complications due to iron overload, it is important to assess iron chelation in this patient population as they are not candidates for phlebotomy due to the underlying anemia. Disclosures Taher: Novartis: Honoraria, Research Funding. Porter:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Vifor International: Membership on an entity's Board of Directors or advisory committees. Kattamis:Novartis: Consultancy, Honoraria, Speakers Bureau. Viprakasit:Thai Government: Employment; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Government Pharmaceutical Organization of Thailand: Honoraria, Research Funding. Lawniczek:Novartis Pharma AG: Employment. Pereno:Novartis Pharma AG: Employment. Schoenborn-Kellenberger:Novartis Pharma AG: Employment. Cappellini:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genzyme: Membership on an entity's Board of Directors or advisory committees.

Abstract 4854 Background Approximately 60–80% of patients with myelodysplastic syndromes (MDS) require ongoing red blood cell (RBC) transfusions due to impaired hematopoiesis. Iron chelation therapy has been extensively studied in thalassemia major patients; however, there are fewer data available on the efficacy and safety in transfusion-dependent patients with MDS who have a completely different clinical scenario (Angelucci E and Di Tucci AA. Leuk Res 2009;33:743–4). Increasing evidence is being reported in the literature on the rate and site of iron accumulation (Di Tucci AA et al. Haematologica 2008;93:1385–8), on the impact of transfusion dependency and iron overload on survival (Malcovati L. Leuk Res 2007;31:S2–6, Sanz G et al. Blood 2008;112(11):Abst 640) and on the efficacy of deferasirox (Exjade®) in removing iron in MDS patients. Nevertheless, the possibility to modify clinical outcome by iron chelation in MDS patients is still debated (DeLoughery TG. Am J Hematol 2009;84:263–4). Recent retrospective and prospective non-randomized data (Rose C et al. Blood 2007:110(11);Abst 249) suggest that iron chelation could have a positive impact. A Phase III, prospective, randomized, double-blind, placebo-controlled, parallel-group design clinical trial has therefore been planned to assess the effects of iron chelation therapy with deferasirox on clinical outcomes in patients with MDS (Low/Int-1 risk) and transfusional iron overload. Methods For inclusion, patients must be chelation-naïve, aged ≥18 years with Low/Int-1 risk MDS and serum ferritin (SF) levels of >1000– Conclusions This prospective multicentre study has been designed to investigate the clinical benefit of chelation therapy with deferasirox in patients with MDS, a matter that has assumed increasing relevance during recent years. Disclosures Bowen: Novartis: Honoraria, Research Funding. Magalhães:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Research Funding. Lawniczek:Novartis Pharma AG: Employment. Douma:Novartis Pharma AG: Employment. Jakobs:Novartis Pharma AG: Employment.

Abstract 1768 Poster Board I-794 Background Assessment of the safety profile, in particular renal function, of the oral iron chelator deferasirox (Exjade®) is of particular relevance in MDS patients (pts), given their advanced age and associated decline in renal function. This 1-yr pooled analysis characterizes the safety profile of deferasirox in a large population of MDS and non-MDS pts (β-thalassemia [β-thal] and other anemias [sickle cell, Diamond-Blackfan, aplastic and other]), with emphasis on renal function. Methods Analysis is based on 1-yr pooled data from iron-overloaded pts who were enrolled in five open-label deferasirox studies: US02 and US03 (single-arm (SA), Low/Int 1 MDS pts, starting dose 20 mg/kg/day); 2409 (SA, pts with transfusional hemosiderosis, starting dose 20 mg/kg/day); 107 (randomized trial in β-thal pts, dosing 5–40 mg/kg/day) and 108 (SA, pts with chronic anemias, dosing 5–40 mg/kg/day). Datasets pooled: baseline (BL) characteristics, dosing, transfusion, adverse events (AEs) and laboratory data. Results 1798 pts were assessed (951 β-thal; 584 MDS, 263 other). MDS pts were older (median age 71 yrs) compared with those with β-thal (25 yrs) and other anemias (38 yrs). Mean actual dose of deferasirox (mg/kg/day): β-thal pts 23.5; MDS pts 20.3; other 19.9. Mean transfusional iron intake (mg/kg/day): 0.34, 0.32 and 0.23 in β-thal, MDS and other anemias, respectively. At 1 yr, 88%, 53% and 69% of β-thal, MDS and other pts remained in the study, respectively. Most frequent reasons for discontinuation: AEs (n=42 [4%] β-thal; n=115 [20%] MDS; n=34 [13%] other anemias). Frequency of drug-related AEs was similar for MDS (68%) and other anemias (63%) compared with 49% for β-thal. Most common drug-related AEs in β-thal, MDS and others, respectively, were: diarrhea (11%; 37%; 23%), nausea (7%; 15%; 20%), vomiting (3%; 8%; 8%); rash (11%; 8%; 6%); abdominal pain (6%; 7%; 8%) and upper abdominal pain (4%; 5%; 8%). 64 deaths occurred (none assessed as related to deferasirox by the investigator); 4 (primarily cardiac), 47 (primarily infections, hemorrhages, progression to AML, cardiac events) and 13 (primarily infections) in the β-thal, MDS and other pts, respectively. BL versus last available creatinine clearance (CrCl) were analyzed graphically for MDS pts with/without investigator-reported renal dysfunction AEs (Figure). CrCl for the majority of β-thal and non-MDS pts was >60 mL/min at BL (not shown), while in the MDS group, as expected, there were more pts with CrCl 70 yrs with primarily pre-existing chronic renal insufficiency, diabetes, hypertension and congestive heart failure. Pts with BL CrCl 40–60 mL/min had fewer pre-existing conditions, but still had reported renal dysfunction AEs. In about half of cases with BL CrCl Conclusions This comprehensive assessment of MDS and non-MDS pts with transfusional iron overload confirmed the known safety profile of deferasirox; with the most frequent drug-related AEs reported as gastrointestinal events. The findings were also consistent with the clinical features of MDS such as advanced age and co-morbidities. Pts with BL CrCl Disclosures Cappellini: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genzyme: Membership on an entity's Board of Directors or advisory committees. Porter:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Vifor International: Membership on an entity's Board of Directors or advisory committees. Greenberg:Amgen: Consultancy, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Lawniczek:Novartis Pharma AG: Employment. Glaser:Novartis Pharma AG: Employment. Dong:Novartis Pharmaceuticals: Employment. Gattermann:Novartis: Honoraria, Participation in Advisory Boards on deferasirox clinical trials.