ALBERT

Description: BACKGROUND: Ruxolitinib is a potent JAK1/JAK2 inhibitor that has demonstrated durable reductions in splenomegaly and MF-related symptoms and improved survival compared with placebo and best available therapy in the 2 large phase 3 COMFORT studies. Those studies required baseline platelet (PLT) counts ≥ 100 × 109/L, limiting safety and efficacy data in patients (pts) with lower PLTs; however, thrombocytopenia is frequent in MF. Ongoing phase 2 clinical trials in pts with low PLTs have shown ruxolitinib to be generally well tolerated and to provide efficacy benefits for these pts. To gather additional safety and efficacy data in pts with low PLTs, recruitment for JUMP (JAK Inhibitor Ruxolitinib in Myelofibrosis Patients), a phase 3b expanded-access trial for countries with no access to ruxolitinib outside a clinical trial, was extended to pts with baseline PLT counts ≥ 50 × 109/L. Here, we present safety and efficacy data from a planned interim analysis of ruxolitinib in pts with baseline PLT count ≥ 50 to 〈 100 × 109/L. METHODS: Eligible pts had high-, intermediate-2, or intermediate-1-risk MF, with a palpable spleen (≥ 5 cm from the costal margin) and baseline PLT counts ≥ 50 × 109/L. The starting doses of ruxolitinib was 5 mg bid for pts with baseline PLTs ≥ 50 to 〈 100 × 109/L. The primary endpoint was assessment of safety and tolerability of ruxolitinib based on the frequency, duration, and severity of adverse events (AEs). An interim analysis of the safety and efficacy of ruxolitinib in pts with PLTs ≥ 50 to 〈 100 × 109/L at baseline (low-PLT group) was planned for when the first 50 low-PLT pts had completed 6 mo of therapy; this analysis includes results from the first 6 mo of treatment. The final analysis will be performed after all pts have completed 24 mo of treatment or ended treatment due to commercial availability. RESULTS: At data cutoff (01 January 2014), 50 pts with low PLTs had been treated for 6 mo and are included in this analysis. Pt characteristics were median age, 68.5 years; median palpable spleen length, 15.5 cm below the costal margin; and female, 50.0%. Median (range) baseline hemoglobin (Hb) was 98 g/L (57-149 g/L) and PLT count was 87 × 109/L (68 to 98 × 109/L). Most pts (76.0%) remained on or completed treatment as per protocol at the time of data cutoff. The primary reasons for discontinuation included adverse events (AEs; n = 9) and disease progression (n = 2). The median daily dose was 11.8 mg/day (range, 5.9-40.0 mg/day). Of evaluable pts at week 24, 38.2% (13/34 pts) achieved a ≥ 50% reduction from baseline in palpable spleen length; 38.2% had reductions of ≥ 25% to 〈 50%. Overall, 44.7% of pts achieved a ≥ 50% reduction from baseline in spleen length at any time. Clinically meaningful improvements in symptoms, as assessed using the FACT-Lymphoma Total Score (the range for the minimally important difference is 6.5 to 11.2 points), were seen as early as week 4 (mean change from baseline, 8.2) and were durable through week 12 (9.6). The most common hematologic grade ≥ 3 AEs were anemia (28.0%) and thrombocytopenia (30%; 4% grade 4); 3 pts discontinued due to thrombocytopenia and 1 due to anemia. Four pts had grade 1/2 hemorrhages (1 conjunctival, 1 gastric, and 2 epistaxis) and 2 pts had grade 3/4 (1 intestinal and 1 esophageal varices). PLT counts decreased slightly from baseline (mean change at nadir, −5.9 × 109/L); 3 pts required PLT transfusions. The mean change from baseline to nadir in Hb was −13.4 g/L. Rates of nonhematologic grade ≥ 3 AEs were low overall (1 pt each), with the exception of pyrexia (6.0%), septic shock (4.0%), and arthralgia (4.0%); 44.0% of pts had ≥ 1 dose modification and 28.0% had ≥ 1 dose interruption. CONCLUSIONS: In this cohort of pts with low PLTs, ruxolitinib demonstrated an AE profile consistent with that previously reported in pts with normal PLTs. As compared to a previous analysis of pts with median baseline PLT counts of 248 × 109/L from this same study (Al-Ali et al. EHA 2014), pts in this low-PLT cohort experienced similar improvements in symptoms (mean change from baseline at week 12, 9.6 vs 11.8) but lower achievement of a ≥ 50% reduction from baseline in spleen length within the first 24 weeks of treatment (44.7% vs 69%), likely due to the lower median daily dose (11.8 mg/day vs 36.8 and 24.0 mg/day for pts with starting doses of 20 and 15 mg bid, respectively). Taken together, these data suggest that low-dose ruxolitinib is generally safe and efficacious in pts with PLTs ≥ 50 to 〈 100 × 109/L. Disclosures Griesshammer: Roche: Honoraria; Sanofi: Honoraria; Novartis: Honoraria; Shire: Honoraria; Amgen: Honoraria. Vannucchi:Novartis Pharmaceuticals Corporation: Consultancy, Honoraria, Research Funding. le Coutre:Pfizer: Honoraria; BMS: Honoraria; Novartis: Honoraria, Research Funding; Ariad: Honoraria. Al-Ali:Celgene: Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Gupta:Incyte Corporation: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Foltz:Promedior: Research Funding; Gilead: Research Funding; Incyte: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Janssen: Consultancy. Bouard:Novartis: Employment. Perez Ronco:Novartis: Employment. Ghosh:Novartis: Employment.

Description: BACKGROUND: Ruxolitinib is a potent JAK1/JAK2 inhibitor that has demonstrated durable reductions in splenomegaly and myelofibrosis (MF)-related symptoms. Additionally, ruxolitinib proved superior to placebo and best available therapy in the phase 3 COMFORT studies and showed improved survival. In some patients (pts) receiving ruxolitinib, adverse events (AEs) may lead to treatment interruption; in such pts, AE management, dose optimization, and efficacy expectations may be balanced. This analysis provides further information about the efficacy and safety of ruxolitinib in pts who have restarted treatment after treatment interruption (cutoff date, 01 January 2014) in the JUMP (JAK Inhibitor Ruxolitinib in Myelofibrosis Patients) trial, a large, phase 3b, expanded-access program. METHODS: Pts with MF classified as high risk, intermediate-2 risk, or intermediate-1 risk, with a palpable spleen (≥ 5 cm from the costal margin), received starting doses of ruxolitinib based on their platelet counts at baseline (5 mg twice daily [bid; ≥ 50 to 〈 100 × 109/L], 15 mg bid [100 to 200 × 109/L], or 20 mg bid [〉 200 × 109/L]). Endpoints included safety and tolerability, as well as changes in spleen length, symptoms, and laboratory values. This analysis included all pts who started study treatment ≥ 1 year before data cutoff and had ≥ 1 dose interruption of ≥ 7 days. RESULTS: This analysis included 207 pts (primary MF, 68.1%; female, 53.1%; median age, 69 years) presenting with baseline medians: spleen length, 13 cm (range, 1.0-35.0 cm); hemoglobin, 99 g/L (50.7% of pts with 〈 100 g/L); and platelets, 199.5 × 109/L. At data cutoff, most pts (60.9%) remained on treatment (38.2%) or completed treatment per protocol (22.7%); the main reasons for discontinuation included AEs (18.4%), death (6.8%), disease progression (5.3%), and other (8.7%). Overall, the median duration of exposure was 12.5 months: 1.9 months from baseline to interruption and 6.5 months after restart. The mean daily dose was 30.5 mg prior to treatment interruption and 19.4 mg after treatment restart. Dose interruptions lasted 7 to 14 days in 41.1% of pts (15 to 21 days, 26.6%; 〉 21 days, 32.4%) and were mostly due to AEs (92.3%). Most pts (67.1%) had only 1 dose interruption. At weeks 12, 24, and 48, overall 45%, 53%, and 54% of pts, respectively, achieved a ≥ 50% reduction from baseline in palpable spleen length. In addition, at the same time points, 29%, 23%, and 23% achieved reductions from 25% to 50%. 68.2% (133/195) of pts experienced a ≥ 50% reduction at any time; 77 pts (58%) achieved it before interruption and 56 pts (42%) after restart. From spleen length at restart, 24% of pts achieved a further 50% reduction, 9% experienced a spleen length increase ≥ 50%, and 67% remained stable in between. Clinically meaningful improvements in symptoms (the range for the minimally important difference is 6.5 to 11.2 points), as assessed by the FACT-Lymphoma Total Score, were observed as early as week 4 (mean change from baseline, 9.6), with a trend toward improvement at week 48 (6.1). The most common hematologic grade 3/4 AEs were anemia (43.5%) and thrombocytopenia (41.1%), leading to permanent discontinuations in 9 (4.4%) and 14 pts (6.8%), respectively. Rates of nonhematologic AEs grade ≥ 3 were low (≤ 2%), except for pneumonia (5.8%), abdominal pain (3.4%), urinary tract infection (3.4%), increased γ-glutamyltransferase (2.4%), asthenia (2.4%), and dyspnea (2.9%), but these rarely led to discontinuations (≤ 1%). Despite 〉 3-times longer exposure after restart, the rates of AEs before ruxolitinib interruption and after treatment restart were similar overall. CONCLUSIONS: In this cohort of pts, ruxolitinib provided reductions in spleen size and symptoms prior to and after treatment interruption. After restart of treatment, pts were able to stay on ruxolitinib at a median dose of ≈ 10 mg bid, and most pts did not require another interruption. Rates of AEs did not increase after treatment restart, with rates of some AEs decreasing; discontinuation rates after restart of treatment are comparable to those observed in the overall study population (Al-Ali et al. EHA 2014). Overall, ruxolitinib is generally safe and well tolerated and provides meaningful reductions in splenomegaly and symptoms in pts who have restarted ruxolitinib after treatment interruption. Disclosures Gupta: Novartis: Consultancy, Honoraria, Research Funding; Incyte Corporation: Consultancy, Research Funding. Griesshammer:Shire: Honoraria; Novartis: Honoraria; Sanofi: Honoraria; Roche: Honoraria; Amgen: Honoraria. Foltz:Novartis: Consultancy, Honoraria, Research Funding; Incyte: Research Funding; Gilead: Research Funding; Promedior: Research Funding; Janssen: Consultancy. Al-Ali:Novartis: Consultancy, Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Tannir:Novartis: Employment. Ronco:Novartis: Employment. Ghosh:Novartis: Employment. Vannucchi:Novartis Pharmaceuticals Corporation: Consultancy, Honoraria, Research Funding.

Description: Rationale for Study Primary Myelofibrosis (PMF) mainly affects individuals in their sixth decade of life or older. It is the most difficult myeloproliferative neoplasm to be defined, as the phenotype mimics a variety of hematological and non-hematological diseases. No symptom or sign is specific for PMF. Many patients are asymptomatic at presentation and the disease is usually detected by the discovery of a splenomegaly or abnormal blood counts during a routine examination. The only treatment with curative potential for PMF is allogeneic stem cell transplantation. This should be reserved only for high-risk patients, after careful consideration, taking into account the option for participation in clinical trials of new drugs. It is therefore extremely important the early identification of poor prognosis patients, to offer the best therapy. In Brazil, we do not have sufficient data to assess a patient's journey between the first symptoms and diagnosis of PMF. Moreover, the real incidence/ prevalence of this disease is unknown and a sub-diagnosis rate is speculated in our country. Objectives Understand and identify the journey of patients with PMF (clinical characteristics, diagnosis process and therapeutics interventions) and the problems between the first symptoms and initiation of treatment. Methods Given the observational nature of the study and the lack of a specific hypothesis to be tested, the statistical analysis is descriptive. This partial analysis includes descriptive results of contents of the database. Categorical data are presented as frequencies and percentages. For continuous data, mean, standard deviation, median, minimum, and maximum values are presented. Results 103 patient disposition (2008-2012); all of them met WHO criteria 2008: median age: 69; 58% male and 13.6% had died. Based on medical history, professional or environmental exposure was related in 4%, but this information was lack in 25% of the medical charts. In almost 42% of the medical records, the family history was not available. Two patients had a positive family history (brother of one and sister from another one with the same disease). Most frequent reason (63,1%) for medical evaluation seeking was symptoms and fatigue happened in 67% of them. Time from symptoms onset date until the confirmed diagnosis took a median of 9.7 months. General physician was the most frequent specialist to do the first evaluation of the patient until confirmed or suspected diagnosis. Bone marrow aspiration and bone marrow biopsy were performed in all patients; mutation status for JAK V617F in 82.5%, PCR for BCR-ABL in 71.8% and bone marrow cytogenetics in 64.1%. According to IPSS (78 patients), 8.5 % were low risk, 63.4% intermediate-1 63.4%, intermediate-2 28.1% and none high risk. Anemia was the most frequent laboratorial finding (67%) and most of the patients were treated with hydroxiurea (75.7%). Conclusions Although most of the patients have apparently the diagnosis of PMF, it took almost 10 months to be done. An expressive number of medical reports do not show a complete history, while 20-30% of them don’t have all the laboratory tools for a precise diagnosis. It is important to know Brazilian needs to improve diagnostic and provide a better treatment, since we are facing new drugs for PMF. Disclosures: No relevant conflicts of interest to declare.

Description: BACKGROUND Ruxolitinib is a potent JAK1/JAK2 inhibitor that has demonstrated reductions in splenomegaly and disease-related symptoms, as well as improved survival, in patients with MF and has proved superior to placebo and best available therapy in the 2 phase 3 COMFORT studies. JUMP (JAK Inhibitor Ruxolitinib in Myelofibrosis Patients) is a phase 3b, expanded-access trial for countries with no access to ruxolitinib outside a clinical trial and was designed to assess the safety and efficacy of ruxolitinib in patients with MF. As of 03 June 2014, 2027 patients have been enrolled in 25 countries, with a planned enrollment of 2500 patients. METHODS Eligible patients had MF classified as high risk, intermediate (Int)-2 risk, or Int-1 risk, with a palpable spleen (≥ 5 cm from the costal margin). Patients received starting doses of ruxolitinib based on platelet counts at baseline (5 mg twice daily [bid; ≥ 50 to 〈 100 × 109/L], 15 mg bid [100 to 200 × 109/L], or 20 mg bid [〉 200 × 109/L]). The primary endpoint was assessment of safety and tolerability of ruxolitinib. Additional analyses included changes in palpable spleen length and symptom scores as measured by the FACT-Lymphoma Total Score (FACT-Lym TS). The final analysis will be performed after all patients have completed 24 months of treatment or ended treatment due to commercial availability. RESULTS This analysis includes results for 1144 enrolled patients (primary MF, 58.8%; n = 673) who started treatment ≥ 1 year before the data cutoff date (01 Jan 2014). At baseline, median age was 68 y (range, 18-89 y); 46.7% were female; median palpable spleen length was 13 cm below the costal margin; median hemoglobin was 105 g/L (range, 44-200 g/L) and 40.3% of patients had hemoglobin levels ˂ 100 g/L; median platelet level was 256 × 109/L (75-1910 × 109/L); mean FACT-Lym TS was 41.9. Most patients (69%) remained on treatment (35.5%) or completed treatment per protocol (33.5%; transition to commercial drug). Primary reasons for discontinuation included adverse events (AEs; 13.8%), disease progression (7.1%), and death (3.8%). Median exposure was 11.1 months; the median average daily dose was 37.2 mg for patients starting at 20 mg bid (64%; n = 728) and 23.4 mg for patients starting at 15 mg bid (33%; n = 374). The majority of patients (75.7%) had dose increases/decreases and 23.9% had a dose interruption. The most common hematologic grade ≥ 3 AEs were anemia (33.0%), thrombocytopenia (12.5%), and neutropenia (3.9%), which led to discontinuation in 2.6%, 3.2%, and 0.3% of patients, respectively. Mean hemoglobin levels declined from baseline (108 g/L) to a nadir of 85 g/L at 8 to 12 weeks and increased to near-baseline levels after week 12; mean platelet levels decreased from baseline (318 × 109/L) to a nadir of 139 × 109/L and remained stable over time. The most common nonhematologic AEs (≥ 10%) were diarrhea (14.5%), pyrexia (13.3%), fatigue (12.9%), and asthenia (12.5%) and were primarily grade 1/2; grade ≥ 3 AEs were low overall (〈 2%), except pneumonia (3.6%), which led to discontinuation in 6 patients (0.5%). Serious AEs were reported for 32.3% of patients. Rates of infections were low; all-grade infections ≥ 5% included nasopharyngitis (6.3%), urinary tract infection (6.0%), and pneumonia (5.3%). Tuberculosis was reported for 3 patients (0.3%; no grade 3/4); no hepatitis B was reported. At weeks 24 and 48, 55% (431/782) and 61% (301/497) of patients achieved a ≥ 50% reduction from baseline in palpable spleen length, respectively; 23% (181/782) and 18% (88/497) had 25% to 50% reductions. Most patients (69%; 733/1062) experienced a ≥ 50% reduction in spleen length from baseline at any time (Figure). Clinically significant improvements on the FACT-Lym TS were seen as early as week 4 and were maintained at week 48 (mean change from baseline: week 4, 11.0; week 48, 9.4; the range for the minimally important difference is 6.5 to 11.2 points). CONCLUSIONS The JUMP study includes the largest cohort of MF patients treated with ruxolitinib reported to date. Consistent with previous reports, the most common AEs were anemia and thrombocytopenia; however, they rarely led to discontinuation. As observed previously, the majority of patients experienced reductions in spleen length and clinically meaningful improvements in symptoms were observed with ruxolitinib treatment. Overall, the safety and efficacy profile of ruxolitinib in JUMP is consistent with that in the phase 3 COMFORT studies. Figure 1 Figure 1. Disclosures le Coutre: Novartis: Honoraria, Research Funding; BMS: Honoraria; Pfizer: Honoraria; Ariad: Honoraria. Griesshammer:Shire: Honoraria; Novartis: Honoraria; Sanofi: Honoraria; Roche: Honoraria; Amgen: Honoraria. Schafhausen:Novartis: Membership on an entity's Board of Directors or advisory committees. Vannucchi:Novartis Pharmaceuticals Corporation: Consultancy, Honoraria, Research Funding. Foltz:Novartis: Consultancy, Honoraria, Research Funding; Incyte: Research Funding; Gilead: Research Funding; Promedior: Research Funding; Janssen: Consultancy. Gupta:Novartis: Consultancy, Honoraria, Research Funding; Incyte Corporation: Consultancy, Research Funding. Tannir:Novartis: Employment. Ronco:Novartis: Employment. Ghosh:Novartis: Employment. Al-Ali:Novartis: Consultancy, Honoraria, Research Funding; Celgene: Honoraria, Research Funding.

Description: Introduction Classical Hodgkin lymphoma (cHL) is one of the most curable cancers, with cure rates ranging from 65-90%, depending on different risk factors. These factors include both clinical (international prognostic score, IPS) and biological markers (tumor associated macrophages, for example). However, most biological biomarkers are not available in a routine basis and IPS does not offer risk stratification for patients diagnosed with early stage cHL. Recently, Porrata et al described the peripheral lymphocyte/monocyte ratio (LMR) as a strong prognostic factor in patients with cHL. In his study, an LMR of less than 1.1 was related with poor outcome. Objectives To assess the role of lymphocyte/monocyte ratio at diagnosis in predicting outcome and survival in cHL patients in Brazil. Patient and Methods This is a retrospective multicenter study conducted by the Universidade Federal de São Paulo, São Paulo, Brazil. Only confirmed cases of cHL, diagnosed between April 1986 to January 2013, with clinical, epidemiological and laboratorial parameters available after a thorough chart review were included in this study. Response was defined as complete (CR) or less than CR (partial response or refractory disease). Event was defined as treatment related mortality, progression (defined as time for initiation of salvage therapy) or relapse. Advanced stage disease was defined as stage I or II with B symptoms and/or bulky disease and stage III or IV. Patients with conflicted data or loss of follow up were excluded from the analysis. Results A total of 570 patients were diagnosed with cHL in this period. However, 303 patients were selected for this study. Nodular sclerosis subtype was diagnosed in 207 (68%) of all patients. Median age at diagnosis was 30 years old (raging from 12-78), with a 0,9:1 Female:Male ratio. The majority (210, 69%) presented with advanced disease. ABVD chemotherapy protocol was the initial therapy in 91% of patients, MOPP/ABV in 8% and 1% of patients received only radiotherapy. For early-stage disease, a median of 6 cycles was delivered and 8 cycles were given for patients with advanced disease. Consolidation radiotherapy was done in 175 (58%) of all patients after chemotherapy. Overall responses were: CR in 90,7% (n=274), Partial response/Refractory disease in 8,9% (n=27); one patient died due to treatment-related toxicity. CR rates were 97,8% in early stage disease and 89,4% in advanced stage (p=0.07). Overall Survival (OS) for the entire group was 95% in 5 years (CI95% 73-83%), with a progression free survival (PFS) of 78% (CI95% 91-97%). A Lymphocyte/Monocyte ratio (LMR) less than 1.1 was not predictive of survival in our patients, neither PFS (84% vs 78%, p=0.30) nor OS (95% vs 96%, p=0.48). However, absolute lymphocyte count (ALC) greater than 1000 cells/mL at diagnosis was related to a better OS (97% vs 88%, p=0.003). Conclusions Although cHL is highly curable, it is an unmet medical need to better stratify these patients at diagnosis, especially with simple and straightforward prognostic factors, such as absolute lymphocyte count at diagnosis. In our study, LMR less than 1.1 was not associated with survival, as recently pointed by Porrata et al., but an ALC greater than 1000 cells/mL was related to better overall survival. It is well known that the incidence of EBV-related cHL, disease presentation and severity are different in developing countries than in developed ones; therefore, prognostic factors may differ from different studied populations, highlighting the importance of our results. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 1884 Brazil is a country of continental dimensions, divided into five regions with ethnic, economical and social heterogeneity. The country is experiencing a rapid and intense demographic transition. Those aged 60 and over represent 10.5%, the fastest growing age group in the population. Myelodysplastic syndromes (MDS) have been reported to differ regarding clinical features, subtype distribution, frequency of abnormal karyotypes and overall survival between Western and Eastern countries, suggesting that ethnic and environmental differences may play a role. This study is a multicenter observational cross-sectional registry. The primary objective was to characterize demographics, clinicopathological features and patterns of care of patients with MDS treated in 12 Brazilian tertiary centers, selected based on clinical expertise and scientific experience. Four hundred and seventy-six patients with date of diagnosis between January/2003 and December/2007 were considered in the analysis: 50.8% were female, the median age at time of diagnosis was 68.3 years, with lower figure in Southern region: 65 years (p=0.02); 86.6% lived in urban area and rural origin was higher in Northeast (p

Description: Abstract 5096 Background Deferasirox is a once-daily oral iron chelator with established dose-dependent efficacy for treating transfusional iron overload. The retrospective multicenter Brazilian trial included patients (pts) from 14 sites of 10 states with a variety of transfusion-dependent anemias and was designed to evaluate the efficacy and safety of fixed starting doses of deferasirox based on transfusion history, with subsequent dose titration based on serum ferritin (SF) trends. Data were available from 105 eligible pts at 6 months of treatment and 73 pts from 1-year follow-up period. Methods Pts (aged ≥ 2 yrs) had transfusion-dependent anemia with a history of multiple transfusions (〉20 transfusions) and/or SF levels ≥ 1000 ng/mL and serum creatinine level 〈 the upper limit of normal (ULN). Deferasirox starting dose was 10-30mg/kg/day depending on transfusion requirements and subsequent dose adjustments of 5-10 mg/Kg/day (range 0–35 mg/kg/d) were done every 3 months based on changes in SF and safety parameters. Efficacy was assessed monthly by measuring change from baseline in SF levels. Safety was evaluated on a monthly basis according to the incidence and type of adverse events and measurement of laboratory parameters, including serum creatinine and liver enzyme levels. Results 105 pts (40 M, 65 F; mean age 25.0±16.6 yrs) were enrolled; 46% (n=48) aged 40 units of red blood cell (RBC); 71.5% (n=75) were on regular RBC transfusion, 56% of the pts required 〈 2 RBC units/month and 44% between 2 and 4 RBC units/month. Only 63% (n=66) had received prior chelation therapy: deferoxamine (DFO; 51.4%) or DFO/deferiprone combination (11.4%). Sixty-four (61%) pts started on 20 mg/kg/d and 41(39%) 〉 20-30 mg/kg/d, 15.2% of pts had dose increases at a median of 24 weeks after treatment initiation. Mean ± SD SF levels (μg/L) did significantly reduce at 6 months and 12 months compared to baseline (BL) [from 3132.14 ± 2237.47 to 2784.25 ± 1969.7 at 6 months (p=0.0001) and 2327.46 ± 1873.8 at 12 months (p=0.005)]. The proportion of patients with SF levels 〈 2000, 2000-3000 and 〉 3000 μg/L from BL to 6 and 12 months by percentage of patients changed from 36% to 47.5% and 52%; from 26% to 26.5% and 24.5%; from 38% to 26% and 23%, respectively. No patient discontinued the treatment. No death was reported by the investigators during the study. The most common drug-related (investigator-assessed) AEs were mild, transient diarrhea (n=15; 14.3%), rash (n=5; 4.7%), nausea (n=9; 8.5%) and headache (n=6; 5.7%). Seven pts (6.6%) had serum creatinine value 〉33% above BL on two consecutive visits, 3 (2.8%) of whom had creatinine increases above the ULN; there were no progressive increases or renal failure. Eleven (10.5%) pts had an increase in alanine aminotransferase 〈 5x ULN but no one experience increases ≥ 5x ULN; levels were already elevated in all of them. Conclusions This first multicenter Brazilian study confirms deferasirox efficacy in achieving a reduction of iron load across a wide range of pts with transfusion-related iron overload. It also supports the clinical approach to fixed starting dose of deferasirox based on iron intake from ongoing blood transfusions and current iron burden with subsequent individual dose titration every 3 months according to SF trends and safety markers. Deferasirox was generally well tolerated in pediatric and adult pts with a safety profile consistent with data from previous clinical trials. The availability of deferasirox as a once-daily oral iron chelator would potentially facilitate improved compliance, and thereby reduce morbidity and mortality from iron overload. Disclosures No relevant conflicts of interest to declare.

Description: Introduction In 1998, Hasenclever et al published the International Prognostic Factor for patients with advanced stage classical Hodgkin lymphoma (cHL). Since then, the IPS has been considered the most important prognostic score for cHL and has been validated in different populations, and also in early stage cHL. From the seven factors analyzed in the IPS, albumin is the only that can be influenced by environmental, economic and nutritional status. We hypothesized if, in developing countries, albumin should still be a prognostic factor, and if so, what is the ideal cutoff value. Objectives To assess if albumin at diagnosis of cHL patients in Brazil was prognostic for overall survival (OS) and progression free survival (PFS) and what would be the best cutoff. Patient and Methods This is a retrospective multicenter study conducted by the Universidade Federal de São Paulo, São Paulo, Brazil. Only confirmed cases of cHL, diagnosed between April 1996 To January 2013, with clinical, epidemiological and laboratorial parameters available after a thorough chart review were included in this study. Response was defined as complete (CR) or less than CR (partial response or refractory disease). Event was defined as treatment related mortality, progression (defined as time for initiation of salvage therapy) or relapse. Advanced stage disease was defined as stage I or II with B symptoms and/or bulky disease and stage III or IV. Patients with conflicted data or loss of follow up were excluded from the analysis. Results A total of 179 patients were selected for this study. Nodular sclerosis subtype was diagnosed in 125 (68.9%) of all patients. Median age at diagnosis was 28 years old (ranging from 13-76). Only 22.9% of patients presented with early stage disease. ABVD chemotherapy protocol was the initial therapy in 91% of patients. Consolidation radiotherapy was done in 48.6%. Median serum albumin was 3.74 (range: 1.34 – 5.52). Median albumin for patients treated in private hospital was 3.6 (range: 2.7 – 4.7) in contrast to patients treated in public hospitals with a median level of 3.0 (range: 1.34 – 5.52), although this difference was not statistically different. Overall responses were: CR in 90%, Partial response/Refractory disease in 10%; one patient died due to treatment-related toxicity. Overall Survival (OS) for the entire group was 93% in 5 years (CI95% 87-96%), with a progression free survival (PFS) of 79% (CI95% 73-86%). When applying the cutoff of 4g/dL, albumin was not related to OS (91% vs 98%, p=ns) or PFS (85 vs 77%, p=ns). However, an albumin value greater than 2g/dL was related to a better OS (94% vs 71%, p=0.01). Conclusions Prognostic factors may differ from different studied populations. This is particularly truth for albumin, which is the only IPS factor influenced by the environment. In our study, however, albumin was not significantly related to OS or PFS, unless when a cutoff of 2g/dL was used. Disclosures: No relevant conflicts of interest to declare.