Publications (4)23.45 Total impact
-
Article: Hematologic responses to deferasirox therapy in transfusion-dependent patients with myelodysplastic syndromes.
[show abstract] [hide abstract]
ABSTRACT: 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; data on there reductions/improvements have been limited to case reports and small studies. DESIGN AND METHODS: To explore this observation in a large population of patients, we report a post-hoc analysis evaluating hematologic response to deferasirox in a cohort of iron-overloaded patients with myelodysplastic syndromes enrolled in the Evaluation of Patients' Iron Chelation with Exjade(®) (EPIC) study using International Working Group 2006 criteria. RESULTS: Two-hundred and forty-seven, 100 and 50 patients without concomitant medication for myelodysplastic syndromes were eligible for analysis of erythroid, platelet and neutrophil responses, respectively. Erythroid, platelet and neutrophil responses were observed in 21.5% (53/247), 13.0% (13/100) and 22.0% (11/50) of the 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. A reduction in labile plasma iron to less than 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.Haematologica 03/2012; 97(9):1364-71. · 6.42 Impact Factor -
Article: A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with del5q.
[show abstract] [hide abstract]
ABSTRACT: This phase 3, randomized, double-blind study assessed the efficacy and safety of lenalidomide in 205 red blood cell (RBC) transfusion-dependent patients with International Prognostic Scoring System Low-/Intermediate-1-risk del5q31 myelodysplastic syndromes. Patients received lenalidomide 10 mg/day on days 1-21 (n = 69) or 5 mg/day on days 1-28 (n = 69) of 28-day cycles; or placebo (n = 67). Crossover to lenalidomide or higher dose was allowed after 16 weeks. More patients in the lenalidomide 10- and 5-mg groups achieved RBC-transfusion independence (TI) for ≥ 26 weeks (primary endpoint) versus placebo (56.1% and 42.6% vs 5.9%; both P < .001). Median duration of RBC-TI was not reached (median follow-up, 1.55 years), with 60% to 67% of responses ongoing in patients without progression to acute myeloid leukemia (AML). Cytogenetic response rates were 50.0% (10 mg) versus 25.0% (5 mg; P = .066). For the lenalidomide groups combined, 3-year overall survival and AML risk were 56.5% and 25.1%, respectively. RBC-TI for ≥ 8 weeks was associated with 47% and 42% reductions in the relative risks of death and AML progression or death, respectively (P = .021 and .048). The safety profile was consistent with previous reports. Lenalidomide is beneficial and has an acceptable safety profile in transfusion-dependent patients with Low-/Intermediate-1-risk del5q myelodysplastic syndrome. This trial was registered at www.clinicaltrials.gov as #NCT00179621.Blood 07/2011; 118(14):3765-76. · 9.90 Impact Factor -
Article: Subcutaneous or intravenous administration of romiplostim in thrombocytopenic patients with lower risk myelodysplastic syndromes.
[show abstract] [hide abstract]
ABSTRACT: Romiplostim is a peptibody protein that augments thrombopoiesis by activating the thrombopoietin receptor. In this phase 2, multicenter, open-label study, 28 thrombocytopenic patients with lower risk myelodysplastic syndromes (MDS) were assigned to receive romiplostim 750 μg administered subcutaneously either weekly or biweekly or administered as biweekly intravenous injections for 8 weeks. Patients also could enter a 1-year study extension phase. At least 1 adverse event was observed in 93% of patients. The most common adverse events were fatigue and headache (18% for both, and 5 events were grade 3 or 4. There was 1 serious treatment-related adverse event in the biweekly intravenous cohort (hypersensitivity). This hypersensitivity resolved without discontinuation of study treatment. No patients developed neutralizing antibodies or bone marrow fibrosis. Of the patients who completed 8 weeks of treatment, 57% had a complete platelet response, an additional 8% had a major platelet response, and 61% did not require a platelet transfusion during this period. Weekly subcutaneous injections achieved the highest mean trough concentrations. The safety and efficacy profiles of romiplostim in this study suggested that weekly subcutaneous administration of 750 μg romiplostim is an appropriate starting dose for future clinical studies in patients with MDS and thrombocytopenia.Cancer 10/2010; 117(5):992-1000. · 4.77 Impact Factor -
Article: Deferasirox in iron-overloaded patients with transfusion-dependent myelodysplastic syndromes: Results from the large 1-year EPIC study.
[show abstract] [hide abstract]
ABSTRACT: The prospective 1-year EPIC study enrolled 341 patients with myelodysplastic syndromes (MDS); although baseline iron burden was >2500ng/mL, approximately 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.Leukemia research 05/2010; 34(9):1143-50. · 2.36 Impact Factor
