Deferasirox in iron-overloaded patients with transfusion-dependent myelodysplastic syndromes: Results from the large 1-year EPIC study

PubMedID: 20451251The prospective 1-year EPIC study enrolled 341 patients with myelodysplastic syndromes (MDS); although baseline iron burden was >2500. ng/mL, ~50% were chelation-naïve. Overall median serum ferritin decreased significantly at 1 year (p=0.002). Decreases occurred irrespective of whether patients were chelation-naïve or previously chelated; changes were dependent on dose adjustments and ongoing iron intake. Sustained reductions in labile plasma iron were observed. Discontinuation rate (48.7%) and adverse event profile were consistent with previously reported deferasirox data in MDS. Alanine aminotransferase levels decreased significantly; change correlated significantly with reduction in serum ferritin (p<0.0001). This large dataset prospectively confirms the efficacy and well characterizes the safety profile of deferasirox in MDS. © 2010 Elsevier Ltd.NovartisContributions : NG, CF, MDP, PF, AG, AG-B, MS, KT, DV and CR served as investigators on this trial, enrolling patients and contributed to data interpretation, reviewed and provided their comments on this manuscript. DH and GD coordinated the execution of the trial and contributed to the analysis, interpretation and reporting of the trial data. BR served as the trial statistician. Funding : The study was sponsored by Novartis Pharma AG (Basel, Switzerland) and designed by the sponsor in consultation with a board of expert hematologists. The sponsor and research organization working under contract for the sponsor monitored the investigational sites, collected and managed the data, and conducted the statistical analysis. An independent Study Monitoring Committee (SMC) oversaw the execution of the study and the lead investigators and SMC had access to the final study data and provided significant contributions to the data interpretation. Dr Gattermann prepared the manuscript with the assistance of a medical writer. Financial support for medical editorial assistance was provided by Novartis. All other named authors contributed to the interpretation of the results, critically reviewed and commented on the manuscript, and approved the final version before submission. Dr Gattermann made all final decisions about all aspects of publication. We thank Andrew Jones, PhD for medical editorial assistance with this manuscript. Appendix

: Qual Life Res

International audiencePURPOSE: Tyrosine kinase inhibitors (TKIs) have dramatically improved the prognosis of chronic myeloid leukemia (CML). We aimed to assess health state utility and quality of life (QoL) in French patients with CML in real-life setting, to study the determinants of utility score and to compare health-related QoL values to general population norms. METHODS: We conducted a cross-sectional study in 412 patients with CML. Data were collected by electronic survey. Three patient-reported outcomes questionnaires were used: EORTC QLQ-C30, EORTC QLQ-CML24 and EuroQol EQ-5D-3L. Health state utility values were computed using the French value set. We computed deviations from reference norms from the general population. We studied the determinants of health utility score using multiple regression models. RESULTS: The mean utility score (SD) was 0.72 (0.25) in the chronic phase and 0.84 (0.21) in treatment-free remission, with marked variations by gender. Patients with CML had a deviation from the reference norm of -0.15 on average (SD: 0.25). In terms of QoL, social functioning, role functioning and cognitive functioning were notably impacted with a mean difference of -16.0, -13.1 and -11.7 respectively. Fatigue, dyspnea and pain were the symptoms with the highest deviation from general population norms (mean difference of 20.6, 14.0 and 8.3 respectively). In the multiple regression analysis, fatigue was the most important independent predictor of the utility score. CONCLUSION: Although TKIs prevent the disease from progressing and even allow remission without treatment, QoL in patients with CML is notably altered. The utility scores deteriorate with CML symptoms

Subcutaneous or intravenous administration of romiplostim in thrombocytopenic patients with myelodysplastic syndrome (MDS)

7009 Background: Thrombocytopenia is common in patients (pts) with MDS, and treatment options are currently limited to platelet (plt) transfusions. Romiplostim is an Fc-peptide fusion protein (peptibody) that stimulates plt production by the same mechanism as thrombopoietin. Methods: This was a phase II, multicenter, single arm, open-label study. Eligibility criteria included IPSS low or intermediate-1 risk MDS and a mean baseline plt count ≤50x10 9 /L. Safety and efficacy of romiplostim were evaluated in pts receiving 750μg romiplostim according to one of 3 schedules: weekly or biweekly subcutaneous injections (QWSC or Q2WSC), or biweekly intravenous injections (Q2WIV). Plt responses were measured per IWG 2006 criteria. Results: Of the 28 pts enrolled, 17 (61%) completed the study; 22 (79%) were male and the mean (±SD) baseline plt count was 29 (±10) x 10 9 /L. The mean age was 71 years and 19 pts (68%) had received plt transfusions in the past year. Mean duration of exposure to romiplostim was 12 (±8) weeks. The most common adverse events (AEs) were fatigue and headache (both 18%). Five pts experienced serious AEs, and there were 2 cases of disease progression to AML: one pt in the QWSC cohort who received romiplostim for 4 weeks and one in the Q2WSC cohort who received romiplostim for 20 weeks. For pts who completed 8 weeks treatment, 15/23 (65%) achieved a plt response, defined by IWG 2006 criteria, and 14/23 (61%) did not require a plt transfusion during this period. The small number of pts limited the ability to compare administration schedules; minor differences were observed in plt responses and plt transfusions, and the incidence of AEs appeared similar among cohorts. Conclusions: IV and SC romiplostim appeared well-tolerated and effective in raising plt counts and avoiding plt transfusions in low and intermediate-1 risk MDS pts. The dose recommendation for future studies is 750μg, given QW or Q2W SC. [Table: see text] [Table: see text

Clinical management of gastrointestinal disturbances in patients with myelodysplastic syndromes receiving iron chelation treatment with deferasirox

Item does not contain fulltextMyelodysplastic syndromes are characterized by ineffective hematopoiesis resulting in peripheral cytopenias. The majority of patients is dependent on regular transfusions of packed red blood cells leading to a secondary iron overload which might result in organ damage. Therefore, sufficient iron chelation therapy in selected patients is mandatory. Deferasirox (DFX) is an orally administered iron chelator which has been highly efficient in the treatment of secondary iron overload. Most frequent side effects of DFX are gastrointestinal disturbances, which leads in some patients to low adherence to the therapy. An expert panel met in Lisbon in July 2010 to develop recommendations on prevention and management of GI disturbances based on existing data and personal experiences

CML patients show sperm alterations at diagnosis that are not improved with imatinib treatment

International audienc

Hematologic responses with deferasirox therapy in transfusion-dependent myelodysplastic syndromes patients.

Background: Reductions in transfusion requirements/improvements in hematologic parameters have been associated with iron chelation therapy in transfusion-dependent patients, including those with myelodysplastic syndromes; these data have been limited to case reports and small studies. Design and methods: To explore this observation in a large patient population, we report a post-hoc analysis evaluating hematologic response to deferasirox in a cohort of iron-overloaded myelodysplastic syndromes patients enrolled in the Evaluation of Patients’ Iron Chelation with Exjade® (EPIC) study using International Working Group 2006 criteria. Results: 247, 100 and 50 patients without concomitant myelodysplastic syndromes medication were eligible for erythroid, platelet and neutrophil response analyses. Erythroid, platelet and neutrophil responses were observed in 21.5% (53/247), 13.0% (13/100) and 22.0% (11/50) of patients after a median of 109, 169 and 226 days, respectively. Median serum ferritin reductions were greater in hematologic responders compared with non-responders at end of study, although these differences were not statistically significant. Reduction in labile plasma iron to <0.4 μmol/L was observed from week 12 onwards; this change did not differ between hematologic responders and non-responders. Conclusions: This analysis suggests that deferasirox treatment for up to 1 year could lead to improvement in hematologic parameters in some patients with myelodysplastic syndromes