ALBERT

Description: Background: Diseases whose treatment requires chronic transfusion therapy are relatively rare, and many have higher prevalence among certain ethnic groups and geographic regions. In these geographical regions, the patterns of care for these diseases and the epidemiology of iron overload (IOL) and other complications of treatment are currently undefined. To improve patient (pt) outcomes, it is important to understand how to diagnose, monitor, and manage these diseases. The TORS study aimed to collect information on a large number of newly diagnosed pts with various types of anemia and hemoglobinopathies to assess pt management considering diagnostic criteria and treatment pattern with iron chelation therapy (ICT) across various geographical regions. Methods: Inclusion and exclusion criteria were defined earlier by Siritanaratkul et al, EHA. 2015. Pts aged 〉2 years requiring chronic transfusion therapy with newly diagnosed anemias (

Description: Abstract 2410 Poster Board II-388 BACKGROUND: Eltrombopag (PROMACTA®; GlaxoSmithKline, Collegeville, PA, USA) is an oral, small molecule, thrombopoietin receptor agonist that is approved in the US for the treatment of chronic immune thrombocytopenic purpura (ITP) and is being evaluated for the treatment of thrombocytopenia of various etiologies (eg, chronic liver disease, hepatitis C, MDS, chemotherapy). The prevalence of hepatobiliary laboratory abnormalities (HBLAs) in the overall population of chronic ITP patients, specifically ALT 〉3× ULN (4.6%), has been shown to be relatively high compared with other disease populations (Bennett Haematologica 2009). OBJECTIVE: To evaluate the effects of eltrombopag on the liver by analyzing HBLAs across the ITP clinical program. METHODS: Data were collected and analyzed from patients in 3 randomized, placebo-controlled (TRA100773A, TRA100773B, RAISE) and 2 open-label (REPEAT, EXTEND) eltrombopag studies. The analysis followed an FDA draft guidance on Drug-Induced Liver Injury (DILI), taking into consideration ALT or AST ≥3× ULN, total bilirubin or alkaline phosphatase (AP) 〉1.5× ULN, and potential combinations of these HBLAs. RESULTS: In the 3 placebo-controlled studies, 7% (9/128) of placebo patients and 11% (33/299) of eltrombopag patients met at least 1 of the DILI screening criteria (Table 1). In these studies, a similar incidence of abnormalities was observed in both treatment groups with the exception of ALT ≥3× ULN (placebo 2%; eltrombopag 5%). Total bilirubin elevations were observed in 3% and 4% of patients in the placebo and eltrombopag groups, respectively. 3 patients (2%) on placebo and 4 patients (2%) on eltrombopag were withdrawn due to elevations of ALT and/or total bilirubin. In REPEAT, 5% (3/66) of patients met at least 1 of the DILI screening criteria. Results in EXTEND were similar with 24 patients (8%) meeting at least 1 of the DILI screening criteria and 5 patients (2%) being withdrawn due to an HBLA. 18 EXTEND patients met at least 1 of the DILI screening criteria in a previous eltrombopag study. Of these, 7 patients (39%) met at least 1 of the DILI screening criteria during EXTEND; 5/7 experienced the same HBLAs as in the previous study. The recurrent HBLAs were generally of a lesser magnitude than the initial ones. In studies in which fractionation was required, 17 of the 18 patients with total bilirubin 〉1.5× ULN had hyperbilirubinemia due to indirect bilirubin. Bilirubin was not fractionated in 1 patient. Of the 60 eltrombopag-treated patients with HBLAs across the program, 25 patients (42%) had their elevations resolve despite continued eltrombopag treatment. Across the program, 5 patients had ALT 〉3× ULN and bilirubin 〉1.5× ULN (Table 1). Of these 5 patients, 3 provisionally met Hy's Law criteria (ALT 3× ULN and bilirubin 〉2× ULN). Ultimately, however, none of these patients met Hy's Law criteria as 1 patient had an increase in indirect bilirubin and 2 patients had confounding factors: 1 with acute cholangitis and 1 with septicemia and right-sided congestive heart failure. None of the patients experiencing HBLAs was reported to present with clinical symptoms indicative of liver function impairment. CONCLUSION: Eltrombopag treatment can lead to an elevation of ALT or indirect bilirubin. In clinical trials, these elevations have been typically mild, reversible and not accompanied by clinical symptoms indicative of impaired liver function. Disclosures: Maddrey: GlaxoSmithKline: Consultancy. Cheng:GlaxoSmithKline: Research Funding. Wroblewski:GlaxoSmithKline: Employment. Brainsky:GlaxoSmithKline: Employment.

Description: Introduction: β-thalassemia is an inherited hemoglobinopathy associated with an erythroid maturation defect characterized by ineffective erythropoiesis and impaired RBC maturation. Luspatercept is a first-in-class erythroid maturation agent under development to treat patients with β-thalassemia. Luspatercept binds to select TGFβ superfamily ligands to reduce aberrant Smad2/3 signaling and enhance late-stage erythropoiesis (Suragani RN, et al. Nat Med. 2014;20:408-14). We report the results of a phase 3, randomized, double-blind, placebo-controlled study to determine the efficacy and safety of luspatercept in adult β-thalassemia patients requiring regular RBC transfusions. ClinicalTrials.gov identifier: NCT02604433. Methods: Eligible patients were aged ≥ 18 years; had β-thalassemia or hemoglobin (Hb) E/β-thalassemia (compound β-thalassemia mutation and/or multiplication of α-globin genes was allowed); and required regular transfusions of 6-20 RBC units in the 24 weeks prior to randomization with no transfusion-free period ≥ 35 days during that time. Patients were randomized 2:1 to receive either luspatercept, at a starting dose level of 1.0 mg/kg with titration up to 1.25 mg/kg, or placebo, subcutaneously every 3 weeks for ≥ 48 weeks. Patients in both treatment arms continued to receive RBC transfusions and iron chelation therapy to maintain the same baseline Hb level. The primary endpoint was a ≥ 33% reduction in transfusion burden (with a reduction of ≥ 2 RBC units) during weeks 13-24, when compared with a 12-week baseline period. Key secondary endpoints included: ≥ 33% reduction in RBC transfusion burden at weeks 37-48, ≥ 50% reduction in transfusion burden at weeks 13-24, ≥ 50% reduction in transfusion burden at weeks 37-48, and mean change in transfusion burden at weeks 13-24. Achievement of ≥ 33% reduction in RBC transfusion burden over any consecutive 12 weeks on study was also evaluated. Results: † A total of 336 patients were randomized, of whom 332 were treated. Median age was 30 years (range 18-66) and 58% of patients were female. Patients received a median of 6 RBC units in the 12 weeks prior to treatment. 58% of patients in each arm had undergone splenectomy. B0/B0 genotype (classification according to the HbVar database) was observed in 68 of 224 (30.4%) and 35 of 112 (31.3%) patients in the luspatercept and placebo arms, respectively. 48 of 224 (21.4%) patients in the luspatercept arm achieved the primary endpoint versus 5 of 112 (4.5%) patients receiving placebo (odds ratio 5.79, P 〈 0.0001). 44 of 224 (19.6%) patients receiving luspatercept achieved a ≥ 33% reduction in RBC transfusion burden at weeks 37-48 compared with 4 of 112 (3.6%) patients receiving placebo (P 〈 0.0001). Of 224 patients receiving luspatercept, 17 (7.6%) and 23 (10.3%) achieved a ≥ 50% reduction in RBC transfusion burden at weeks 13-24 and 37-48, respectively, compared with 2 (1.8%) and 1 of 112 (0.9%) patients receiving placebo (P = 0.0303 and P = 0.0017, respectively). The difference of mean change from baseline in transfusion burden from week 13 to week 24 was 1.35 units (P 〈 0.0001). 158 of 224 (70.5%) patients receiving luspatercept achieved a ≥ 33% RBC transfusion reduction over any consecutive 12 weeks compared with 33 of 112 (29.5%) patients receiving placebo (P 〈 0.0001); statistically significant differences were also noted for all other transfusion burden reduction endpoints. Adverse events (AEs) observed in the study were generally consistent with previously reported phase 2 data. Treatment-emergent AEs leading to dose delay or dose reduction were similar between treatment arms. No patient deaths were reported for those treated with luspatercept. Conclusions: Treatment with luspatercept resulted in significant reductions in RBC transfusion burden in adults with transfusion-dependent β-thalassemia. Luspatercept was generally well tolerated in this patient population. † As of May 11, 2018, cutoff date. Disclosures Cappellini: Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Sanofi/Genzyme: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Vifor: Membership on an entity's Board of Directors or advisory committees. Viprakasit:F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Agios: Consultancy, Research Funding; Protagonist Therapeutics: Consultancy, Research Funding. Taher:Protagonist Therapeutics: Consultancy; Novartis: Consultancy, Honoraria, Research Funding; Ionis Pharmaceuticals: Consultancy; La Jolla Pharmaceutical: Research Funding; Celgene Corp.: Research Funding. Georgiev:Alnylam: Consultancy. Coates:Celgene Corp.: Consultancy; ApoPharma: Consultancy, Honoraria; Vifor Pharma: Consultancy; Sangamo: Consultancy, Honoraria. Voskaridou:Acceleron: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene Corp: Membership on an entity's Board of Directors or advisory committees, Research Funding. Forni:Novartis: Research Funding; Roche: Research Funding; Celgene: Research Funding. Perrotta:Acceleron Pharma: Research Funding; Novartis: Research Funding. Lal:Celgene Corporation: Research Funding; Bluebird Bio: Research Funding; La Jolla Pharmaceutical Company: Consultancy, Research Funding; Insight Magnetics: Research Funding; Novartis: Research Funding; Terumo Corporation: Research Funding. Kattamis:ApoPharma: Honoraria; Vifor Pharma: Consultancy; CELGENE: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Vlachaki:Novartis: Honoraria. Origa:Cerus Corporation: Research Funding; Bluebird Bio: Consultancy; Novartis: Honoraria; Apopharma: Honoraria. Aydinok:TERUMO: Research Funding; Protagonist: Other: SSC; CRISPR Tech: Other: DMC; Cerus: Honoraria, Research Funding; La Jolla Pharmaceuticals: Research Funding; Novartis: Research Funding, Speakers Bureau; Celgene: Research Funding. Ho:Takeda: Honoraria, Other: travel to meeting; Novartis: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Celgene: Other: Travel to meeting. Chew:Celgene: Research Funding. Tantiworawit:Celgene: Honoraria, Research Funding, Speakers Bureau. Shah:Novartis: Honoraria, Speakers Bureau; Sobi/Apotex: Honoraria; Celgene Corp: Other: Steering committee; Roche: Other: Advisory board meeting. Neufeld:Celgene Corp.: Consultancy, Other: Steering committee; Acceleron Pharma: Consultancy. Laadem:Celgene: Employment, Equity Ownership. Shetty:Celgene: Employment, Equity Ownership. Zou:Celgene Corporation: Employment, Equity Ownership. Miteva:Celgene Corporation: Employment, Other: grants. Zinger:Celgene Corporation: Employment. Linde:AbbVie: Equity Ownership; Abbott Laboratories: Equity Ownership; Fibrogen: Equity Ownership; Acceleron Pharma: Employment, Equity Ownership. Sherman:Acceleron Pharma: Employment, Equity Ownership. Hermine:AB Science: Consultancy, Equity Ownership, Honoraria, Research Funding; Celgene Corporation: Research Funding; Hybrigenics: Research Funding; Erythec: Research Funding; Novartis: Research Funding. Porter:Cerus: Honoraria; Agios: Honoraria; Novartis: Consultancy. Piga:La Jolla: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bluebird Bio: Honoraria; Apopharma: Honoraria, Research Funding; Celgene Corp: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Acceleron: Research Funding.

Description: Introduction: Eltrombopag is an oral thrombopoietin receptor agonist, approved for the treatment of patients with cITP (persisting 〉12 months) aged ≥1 year, who are refractory to other treatments (eg corticosteroids, immunoglobulins). Pharmacokinetic studies of eltrombopag have demonstrated that patients of East Asian origin (eg Japanese, Chinese, Taiwanese and Korean) experience increased plasma exposure to eltrombopag compared to non-East Asian patients (predominantly Caucasian). As such, the recommended starting dose is 25 mg/day for East Asian patients, compared with 50 mg/day in non-East Asians. In the EXTEND (Eltrombopag eXTENded Dosing) study, all patients, irrespective of ancestry, received 50 mg/day starting dose that was subsequently adjusted to the platelet response. Unpublished anecdotal reports of platelet responses in East Asian patients from EXTEND describe lower doses of eltrombopag. Here, we examine the responses to eltrombopag in East Asian and non-East Asian patients who completed the EXTEND study. Methods : Adult patients (≥18 years old) diagnosed with cITP who had completed a previous ITP study of eltrombopag were enrolled in EXTEND. All patients received eltrombopag starting at 50 mg/day, titrated to 25-75 mg/day or less often as required, based on individual platelet count responses (range ≥50-200x109/L). Maintenance dosing continued after minimization of concomitant ITP medication and optimization of eltrombopag dosing. Patients who received 2 years of treatment and transitioned off due to commercial availability of eltrombopag were considered to have completed the study. Patients could remain on study beyond 2 years until eltrombopag became commercially available. Here we describe the efficacy and durability of response in East Asian and non-East Asian patients. Analyses were conducted using the safety population, defined as all patients who had taken at least one dose of the study medication. Results: Of 302 patients enrolled and exposed to treatment (median duration 2.4 years [range, 2 days to 8.8 years]), 41 (14%) were of East Asian origin. Mean average eltrombopag dose in East Asian and non-East Asian patients was 48.9 (range 4.2-74.9) mg/day and 50.4 (range 1.0-74.6) mg/day, respectively. Maintenance of platelet counts ≥30×109/L for at least 25 weeks was seen in 25/35 (71%) East Asian and 158/222 (71%) non-East Asian patients. In total, 13/35 (37%) East Asian patients and 120/222 (54%) non-East Asian patients maintained continuous platelet counts ≥50×109/L for at least 25 weeks, without rescue therapy (Figure). At the start of response, mean daily dose in East Asian and non-East Asian patients was 45.2 and 45.4 mg/day, respectively. The number of patients receiving dose adjustments according to platelet response was similar in East Asian and non-East Asian patients (Table). Conclusions: Treatment with eltrombopag in East Asian and non-East Asian patients resulted in sustained platelet responses ≥30×109/L for at least 25 weeks in a similar proportion of patients. However, a higher proportion of non-East Asian patients achieved continuous platelet counts ≥50×109/L. Direct comparisons should be interpreted with caution because: a) of limited patient numbers in the East Asian group; b) the possible selection bias of patients entering the EXTEND study following completion of earlier eltrombopag studies, eg, primarily responders; and c) the absence of PK data from these patient groups. All patients received similar doses of eltrombopag irrespective of racial background, and dose modifications according to platelet responses were similar. Further investigations are ongoing to determine whether there were any differences in terms of safety and tolerability outcomes in East Asian and non-East Asian patients. Disclosures Wong: Bayer, Biogen-Idec, Bristol-Myers Squibb, GlaxoSmithKline, Johnson & Johnson, Merck Sharp & Dohme, Novartis, Pfizer, and Roche: Research Funding; Biogen-Idec and Novartis: Membership on an entity's Board of Directors or advisory committees; Bayer, Biogen-Idec and Novartis: Consultancy. Bussel:Amgen, Novartis & GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Boehringer Ingleheim, Prophylix Pharma, Protalex, Rigel Pharmaceuticals: Research Funding; Momenta Pharmaceuticals, Novartis, Prophylix Pharma, Protalex, Rigel Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; UptoDate: Patents & Royalties; Physicians Education Resource: Speakers Bureau. Saleh:GSK: Consultancy, Research Funding, Speakers Bureau. El-Ali:Novartis: Employment. Quebe-Fehling:Novartis: Employment.

Description: Background: EXTEND (June 2006 to July 2015) was an open-label, dose-adjustment extension study to evaluate the safety and efficacy of eltrombopag for the treatment of patients with chronic immune thrombocytopenia (cITP) who had previously been enrolled in an eltrombopag trial. CITP may lead to fatigue and interference with daily activities, and ultimately affect health-related quality of life (HRQoL). Objective: To assess patient-reported HRQoL changes over time during long-term treatment with eltrombopag in patients with cITP using the final EXTEND data. Methods: Four standard validated HRQoL instruments for chronic disease were used in this study: SF-36v2 including the Physical Component Summary (PCS) and Mental Component Summary (MCS) to measure general physical and mental health status; Motivation and Energy Inventory Short Form (MEI-SF) to measure motivation and energy; Fatigue Subscale of FACIT (FACIT-F) to measure symptoms of fatigue; and FACT-Thrombocytopenia Subscale Six-Item Extract (FACT-Th6) to measure concerns related to bleeding and bruising and their impact on usual activities. The instruments were used at baseline (BL) and at a frequency of every 3 months until last on-treatment assessment. Patients were blinded to their current platelet count results before completing the questionnaires. Generalized estimating equations were used to estimate mean changes in HRQoL from BL to different time periods for each instrument, accounting for within-patient correlation. The models adjusted for time period from BL, demographic characteristics, BL clinical characteristics (BMI, BL use of cITP medication, prior splenectomy, prior eltrombopag use, and BL platelet count), and time-varying covariates for rescue therapy use (defined as the composite of new cITP medication, increased dose of cITP medication from BL, platelet transfusion, and splenectomy). Adjusted mean best changes in HRQoL from BL were also estimated using a similar method. Proportions of responders based on minimally important difference (MID) from BL were identified for each of the instruments. Response was defined as a change from BL score of at least one-half the standard deviation (SD) of the normalized scores (5 points) for SF-36v2 PCS and SF-36v2 MCS, at least one-half the SD of BL scores observed across all patients for MEI-SF and FACT-Th6, and at least 3 or 5 points for FACIT-F. Proportions of patients achieving any improvement and time to best improvement from BL were also reported. Results: 302 patients were enrolled in EXTEND. By instrument, 289 to 293 patients had a BL and at least one on-treatment HRQoL assessment for analysis. Median treatment duration was 2.4 years. All HRQoL instruments had positive mean changes from BL over time; noticeably improvements from BL persisted through 5 years of treatment for FACIT-F and FACT-Th6 (nearly all p

Description: Background: ITP is an acquired autoimmune disorder. Second-line treatment options include EPAG, romiplostim (both stimulate platelet production), ritux (a monoclonal anti-CD20 antibody that causes temporary but complete depletion of peripheral B cells), splenectomy (spl), and other immunosuppressive agents. This subanalysis of EXTEND, a global, open-label, extension study, evaluated long-term EPAG in adults with ITP of ≥6 months' duration according to prior ritux use. Aims: Describe efficacy and safety of EPAG in ITP patients (pts) according to prior ritux use. Methods : In EXTEND (Wong et al. Blood 2017;130:2527-36), pts started EPAG at 50 mg/day, with dose adjusted as required to achieve platelet counts of 50-200x109/L. Results: Of 302 pts in EXTEND, 70 (23%) had previously received ritux. Of these pts, mean±SD age was 53±14 years (yrs), median (range) time since diagnosis was 71.3 (12-362) months, 67% were splenectomized, 61% were female, 76% had baseline platelet counts

Description: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by immune mediated platelet destruction causing thrombocytopenia and increase risk of bleeding. Treatment is indicated in patients who present with bleeding or are at risk of bleeding. Corticosteroids (CS) are the main first-line treatment in adult patients, but since not all patients achieve adequate response to CS, most patients require a second line therapy. Rituximab is one of the most widely used second line therapies; its advantages include the ability to induce relatively long lasting remissions after 2-4 infusions and its favorable safety profile. The RITP study was a randomized placebo-controlled trial in which ITP patients who failed to achieve adequate response to CS were randomized to receive rituximab or placebo. The study outcomes were treatment failure (splenectomy or meeting criteria for splenectomy), response rates and duration of response during an 18-month follow-up period. Apart from a longer duration of response in the rituximab arm, the study showed no significant differences in the other outcomes (Ghanima et al. Lancet 2015; 385: 1653-61). The use of stable dose of CS was allowed during the study. This report represents a post-hoc analysis of the RITP trail, restricting the population to those who did not receive any CS during the study, until relapse or treatment failure in the two arms. By this we aimed to eliminate the possible interference resulting from concomitant use of CS on the effect and safety of rituximab and placebo. For effect, we estimated the duration of response, splenectomy rates, platelet counts, and time to bleeding and for safety we estimated time to infection episodes in both arms. We included patients who did not receive CS before treatment failure or relapse or until the end the of the study, if none of the endpoints was achieved. The duration of response was estimated from time of achieving response to relapse (platelet count

Description: Introduction: β-thalassemia is an inherited hemoglobinopathy characterized by ineffective erythropoiesis and anemia. Luspatercept is a first-in-class erythroid maturation agent that binds to select TGF-β superfamily ligands to reduce aberrant Smad2/3 signaling and enhance late-stage erythropoiesis. We aim to evaluate in detail the number of response episodes, duration of clinical benefit, and safety in luspatercept responders during the phase 3 BELIEVE study (NCT02604433). Methods: Eligible pts were aged ≥ 18 years, with β-thalassemia or hemoglobin (Hb) E/β-thalassemia (compound β-thalassemia mutation and/or multiplication of α-globin genes was allowed), requiring regular transfusions of 6-20 RBC units in the 24 weeks (wks) prior to randomization, with no transfusion-free period 〉 35 days. Pts were randomized 2:1 to luspatercept 1.0 mg/kg (up to 1.25 mg/kg allowed), or placebo, subcutaneously every 3 wks for ≥ 48 wks. Pts in both treatment arms continued RBC transfusions to maintain baseline Hb level and iron chelation therapy. Achievement and number of response episodes (defined as ≥ 33% reduction in RBC transfusion from baseline over any consecutive 24 wks) were assessed at a median follow-up of 64.1 wks. Duration of clinical benefit, defined as the time of first response (≥ 33% reduction in RBC transfusion over any 24 wks) to discontinuation due to any cause at that episode, was also assessed. Results:A total of 336 pts were randomized. In the ITT population, 224 pts in the luspatercept arm had a median baseline RBC transfusion burden in the 12 wks prior to randomization of 6.12 U RBCs (average 0.51 U/wk; range 3-14) and the 112 pts in the placebo arm had a median baseline transfusion burden of 6.27 U (average 0.52 U/wk; range 3-12). A total of 194 (57.7%) luspatercept and 65 (58%) placebo pts had prior splenectomy. As of the May 11, 2018 cutoff date, 92/224 (41.1%) luspatercept-treated pts and 3/112 (2.7%) placebo-treated pts had achieved ≥ 33% reduction in RBC transfusion over any 24 wks; of these luspatercept responders, 55 (59.8%) had ≥ 2 separate responses (over the treatment period up to data cutoff), 42 (45.7%) had ≥ 3, 29 (31.5%) had ≥ 4, and 19 (20.7%) had ≥ 5. Three (1.3%) pts receiving luspatercept re-responded at the same dose level after initially losing response. Median duration of clinical benefit (as defined above) for luspatercept responders was 53.5 wks (range 24-93.7). Forty-seven (21.0%) pts receiving luspatercept had no loss of response within the entire study period. Five luspatercept responders achieved RBC transfusion independence for ≥ 24 wks (median total duration was 60.1 wks) and 3 achieved RBC transfusion independence for ≥ 48 wks (median duration was 66 wks). The average number of RBC units saved over any 24 wks in all luspatercept responders was 6.55 U (0.27 U/wk) and was 8.16 U (0.34 U/wk) with transfusion burden 〉 15 U/24 wks, compared to baseline. As of the May 11, 2018 cutoff date, the safety population consisted of 243 pts (including 92 pts who crossed over from the placebo arm to the luspatercept arm). Frequent adverse events (AEs) in the luspatercept and placebo arms included bone pain (19.7% vs 8.3%, respectively), arthralgia (19.3% vs 11.9%), and dizziness (11.2% vs 4.6%). The safety profile for pts who crossed over from placebo to luspatercept was consistent with that observed for pts receiving luspatercept from baseline. The incidence of bone pain, arthralgia, and dizziness was largely non-severe grade 1-2, tended to decrease over time during the study, was not associated with dose level, and was not associated with treatment modification or discontinuation. Pts continue to be monitored for safety outcomes. Conclusions: Most β-thalassemia pts who were luspatercept responders experienced multiple response periods and had durable clinical benefit over the 64.1 wk follow-up period. The incidence of frequent AEs was consistent with the previously reported 48 wk safety profile for luspatercept, was not associated with dose level, and decreased over time with no impact on treatment modification or continuation. Disclosures Viprakasit: Celgene Corporation: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Protagonist: Consultancy, Research Funding; Vifor: Consultancy, Research Funding; Agios: Consultancy, Research Funding; Ionis: Consultancy, Research Funding; La Jolla: Consultancy, Research Funding. Taher:Celgene Corporation: Research Funding; Protagonist Therapeutics: Consultancy, Research Funding; Abfero: Consultancy; Novartis: Consultancy, Honoraria, Research Funding; La Jolla Pharmaceuticals: Consultancy, Research Funding; Ionis Pharmaceuticals: Consultancy. Hermine:AB Science: Consultancy, Equity Ownership, Honoraria, Research Funding; Celgene: Research Funding; Novartis: Research Funding. Porter:Vifor: Honoraria; Agios: Consultancy, Honoraria; Protagonist: Honoraria; La Jolla: Honoraria; Bluebird Bio: Consultancy, Honoraria; Celgene Corporation: Consultancy, Honoraria; Silence Therapeutics: Honoraria. Piga:Acceleron Pharma: Research Funding; Celgene Corporation: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Kuo:Agios: Consultancy; Alexion: Consultancy, Honoraria; Apellis: Consultancy; Bioverativ: Other: Data Safety Monitoring Board; Bluebird Bio: Consultancy; Celgene: Consultancy; Novartis: Consultancy, Honoraria; Pfizer: Consultancy. Coates:agios pharma: Consultancy, Honoraria; celgene: Consultancy, Honoraria, Other: steering committee of clinical study; apo pharma: Consultancy, Honoraria, Speakers Bureau; vifor: Consultancy, Honoraria. Voskaridou:Genesis: Consultancy, Research Funding; Protagonist: Research Funding; Celgene Corporation: Consultancy, Research Funding; Acceleron: Consultancy, Research Funding; Addmedica: Membership on an entity's Board of Directors or advisory committees. Perrotta:Acceleron Pharma: Research Funding; Novartis: Honoraria, Research Funding. Kattamis:Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees; Apopharma: Honoraria; Vertex: Membership on an entity's Board of Directors or advisory committees; ViFOR: Membership on an entity's Board of Directors or advisory committees; Ionis: Membership on an entity's Board of Directors or advisory committees; Novartis Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Laadem:Celgene Corporation: Employment, Equity Ownership. Shetty:Celgene Corporation: Employment, Equity Ownership. Kuo:Celgene Corporation: Employment, Equity Ownership. Miteva:Celgene International: Employment. Zinger:Celgene Corporation: Employment. Sinsimer:Celgene Corporation: Employment, Equity Ownership. Linde:Acceleron Pharma: Employment, Equity Ownership; Abbott Laboratories, Inc.: Equity Ownership; Fibrogen, Inc.: Equity Ownership. Cappellini:CRISPR Therapeutics: Membership on an entity's Board of Directors or advisory committees; Genzyme/Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Honoraria; Vifor Pharmaceutical: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Luspatercept is an investigational therapy that is not approved for any use in any country. Luspatercept is currently being evaluated for potential use in patients with anemia due to myelodysplastic syndromes, beta-thalassemia, or myelofibrosis.

Description: Introduction Immune thrombocytopenia (ITP) is a disease characterized by low platelet count and increased risk of bleeding. However, there has been an increased focus on the risk of thromboembolism particularly venous thromboembolism (VTE) associated with ITP itself and with some of its therapies. Epidemiological studies have shown a doubling in the risk of VTE in ITP patients as compared to the general population. VTE has been reported with various ITP therapies including splenectomy, steroids, IVIG and thrombopoietin receptor agonists (TPO-RAs). In long-term studies on TPO-RAs, arterial and venous thrombosis occurred in 6% of treated patients. Rituximab, a monoclonal antibody directed against CD-20 on the B-cells is widely used as a treatment for ITP. It yields a response rate of 60% and is generally well-tolerated. However, to our knowledge VTE events following treatment with rituximab for ITP have not been reported. Aims We report thromboembolic adverse events encountered in 2 multicenter, randomized controlled trials (RCT) for adult ITP patients treated with rituximab: 1) Rituximab as second-line treatment for adult ITP (the RITP trial)(Ghanima et al, Lancet 2015; 385) and 2) The Rituximab Maintenance Therapy in ITP (The PROLONG Trial; NCT03010202) Methods RITP was a multicenter, randomized placebo-controlled trial in which adult patients with ITP unresponsive to corticosteroid and platelet count 20x10⁹/L. PROLONG is an ongoing multicenter, two-phase RCT. In the first phase, patients with ITP, who fail to achieve an adequate response to corticosteroids (prednisolone or dexamethasone) during the first year after diagnosis are randomized to receive rituximab 1000 mg twice with 15 days apart with or without dexamethasone 20 mg for 4 days starting with rituximab. In the secondphase, responding patients will be randomized at 24 weeks to maintenance therapy with 2 rituximab or placebo infusions separated by 24 weeks. Results Four venous thromboembolic events were reported in 4 patients: 2 of 55 patients who received rituximab in the RITP trial and 2 (one received dexamethasone+rituximab) of 52 patients included so far in the first phase of the PROLONG trial, which results in a VTE rate of 3.7% in the rituximab treated patients. No thromboembolic events were encountered in the placebo arm of the RITP study (n=54 patients, matched on age). Median time from treatment to event was 40.5 weeks, with 2 events occurring 7-14 weeks after the administration of the first dose of rituximab. Median platelet count at the time of VTE was 188x109/L. Characteristics of the 4 patients are shown in the table; none was splenectomized or received thrombopoietic agents before the VTE event. No arterial thromboembolic events were reported in the 2 trials. Conclusion The rate of VTE following treatment with rituximab in these 2 studies seems to be higher than what is expected in an adult ITP population and the general population (Norgaard et al. Br J Haematol. 2016;174). However, based on these results we cannot determine whether the venous thromboembolic events were just incidental events or triggered by the treatment and/or the normalization of platelet count or the presence of risk factors for VTE as old age and immobilization. Table Disclosures Tvedt: Ablynx, alexion and novartis: Consultancy. Michel:Novartis: Consultancy; Amgen: Consultancy; Rigel: Consultancy. Ghanima:Bayer: Honoraria, Research Funding; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Pfizer/BMS: Research Funding.

Description: Background: EXTEND (June 2006 to July 2015) was an open-label, dose-adjustment extension study to evaluate the safety and efficacy of eltrombopag for the treatment of patients with chronic immune thrombocytopenia purpura (cITP) who had previously been enrolled in a pivotal eltrombopag trial. CITP may lead to fatigue and interference with daily activities, and affect patient functioning and experience i.e., health-related quality of life (HRQoL). Objective: To investigate the association between platelet response and HRQoL reported by patients in the EXTEND study, employing widely used and well-validated measures. Methods: Four standard HRQoL instruments were used in this study: SF-36v2 including Physical Component Summary (PCS) and Mental Component Summary (MCS) to measure general physical and mental health status; Motivation and Energy Inventory Short Form (MEI-SF) to measure motivation and energy; Fatigue Subscale of FACIT (FACIT-F) to measure symptoms of fatigue; and FACT-Thrombocytopenia Subscale Six-Item Extract (FACT-Th6) to measure concerns related to bleeding and bruising and their impact on usual activities. The four instruments were used at baseline (BL) and at a frequency of every 3 months until last on-treatment assessment. Patients were blinded to their current platelet count results before completing the questionnaires. HRQoL scores and mean platelet count based on clinical assessments were calculated during time periods post-baseline (BL) to