Efficacy Of Deferasirox In Patients Research Articles

Safety and efficacy of deferasirox in patients with transfusion-dependent thalassemia: A 4-year single-center experience

This study was organized to determine the efficacy and safety of deferasirox (DFX) in reducing the SF of patients with transfusion-dependent thalassemia (TDT). This is a retrospective, descriptive study of 101 transfusion- dependent patients with thalassemia major who were followed for 48 months. Twenty-nine patients who used an alternative chelator either alone or combined, who were not compliant to the treatment, changed the drug due to adverse reactions, and had multiple transfusions and did not complete 4 years of DFX use were excluded. A total 72 out of 101 patients completed the study. SF decreases were noted for the 6-12 and >18-year age groups, from a median of 1532 ng/mL to 1190 ng/mL, and from 1386 ng/mL to 1165 ng/mL, respectively (p > 0.05). The proportion of patients with SF concentrations >2000 ng/mL is decreased (29% at baseline decreased to 15% at the end of the study) during the 48 months. The median SF of those who used <30 mg/kg/day (n = 38) increased from 767 ng/mL to 1006 ng/mL, whereas the >30 mg/kg/day (n = 34) group’s SF concentrations decreased from a median of 1575 ng/mL to 1209 ng/mL (p = 0.029). The decrease of median SF values for Syrian patients was statistically significant (p = 0.043). Most common adverse events were gastric irritation symptoms (19.4%). The total DFX discontinuation ratio was calculated as 9.7%. Although dosages between 25-30 mg/kg/day are adequate to stabilize SF concentrations higher dosages are needed to achieve a statistically significant decrease.

Long-term safety and efficacy of deferasirox in patients with myelodysplastic syndrome, aplastic anemia and other rare anemia in Taiwan

ABSTRACTObjective: Patients with myelodysplastic syndromes (MDS), aplastic anemia (AA) or other rare anemia require chronic blood transfusions which can lead to iron overload and subsequent excess iron-mediated complications. Intensive iron chelation with deferasirox could remove excess iron and can alleviate these events; however, the long-term safety and efficacy in Chinese population are not clearly characterized. This study examined the long-term efficacy and safety of deferasirox in a real-world setting in Taiwan.Methods: This observational, non-interventional, single-arm, multi-center, phase IV study was designed to collect the safety and clinical information about patients who were treated with deferasirox according to investigator’s judgment and in accordance with the general clinical practice.Results: From 2009 to 2011, patients with MDS (N = 38), AA (N = 23), and other rare anemias (N = 18) were enrolled. The mean deferasirox exposure was 17.7 ± 4.02 mg/kg/day. The most common drug-related AEs were skin disorders (32.9%) and gastrointestinal disorders (30.4%), while grade 3–4 AEs were rare (5.1%). In the overall patient population, deferasirox effectively decreased serum ferritin levels at 1 year (P = 0.0154) and 3 years (P = 0.0424) from the baseline. Upon the use of deferasirox, 32.9% patients showed erythroid response and 16.7% patients had platelet response.Conclusions: For patients with MDS, AA, and other rare anemias, the AEs observed in this 3-year surveillance study with deferasirox were mostly mild or moderate. In addition, the hematological response rate was higher than that in the EPIC study, which primarily enrolled Caucasian patients.

Tolerability and efficacy of deferasirox in patients with transfusional iron overload: results from a German 2-year non-interventional study.

Iron overload (IOL) due to repetitive transfusions of packed red blood cells (pRBC) has a major impact on morbidity and mortality in patients with inherited bone marrow failure syndromes and hemoglobinopathies such as thalassemia and sickle cell disease. However, whether IOL influences the outcome of elderly patients with myeloid malignancies is not yet clear. Moreover, clinical trials have reported high drop-out rates during treatment with the oral iron chelator deferasirox (DFX). Here we report the results of a 2-year prospective observational study that aimed at describing the routine use of DFX in patients with hematological malignancies with regard to safety, efficacy and handling of the drug in a routine setting. A total of 406 patients were included. 58% of the patients were male. Most of the patients had myelodysplastic syndromes (MDS) (68%) and myeloproliferative neoplasms (MPN) (14%). Median time from first transfusion to study enrollment was 1.1 years (0-25.5 years) and most patients were chelation naive (91%) at enrollment. With regard to transfusion burden, most of the patients were moderately or mildly transfusion-dependent with 53% receiving 2-4 and 27% receiving less than 2 units of pRBC per month. Serum ferritin decreased from a mean of 2305 μg/l (± 1449 μg/l) to a mean of 1910 μg/l (± 1529 μg/l) at 24 months. There was no substantial change in transfusion-dependence during the observation period. Dose adjustments were reported in 48% of the patients with dose-escalation strategies being the most frequent reason for dosage increases (49%). The median observation time was 355days (5-1080days). Median duration of exposure to DFX was 322days (2-1078days). Two-hundred and ninety (72%) patients discontinued the trial prematurely after a median time of 235days (1-808days). Death (29%) and adverse events (23%) were the main reasons for discontinuation. Eleven percent of the patients discontinued treatment due to sufficient decrease in serum ferritin. Most frequent adverse events were decrease in creatinine clearance (22%), increase in serum creatinine (18%) and diarrhea (16%). This descriptive trial confirms the efficacy of DFX in decreasing the serum ferritin. Moreover, the high drop-out rates seen in prospective trials are recapitulated in this study, which can be attributed to adverse events in a substantial proportion of patients.

The Safety and Efficacy of Deferasirox for the Transplant Patients with Iron Overload

Introduction: Iron overload in patients who received hematopoietic cell transplantation (HCT) is one of the major clinical issues. Although deferasirox is well known to be an iron chelating agent, its safety for the patients who received HCT is unknown. Then, we designed a multicenter prospective study (phase 1) to evaluate the safety and efficacy of deferasirox in patients with iron overload after HCT.Methods: The eligibility criteria includes the duration at least 6 month after HCT, serum ferritin more than 1,000 ng/ml, red blood cell (RBC) transfusions more than 20 units, disease remission, normal renal function, performance status of 0 or 1, and the unfit of phlebotomy. The exclusion criteria were history of iron chelating therapy after HCT, presence of moderate or severe chronic graft-versus-host disease (GVHD), uncontrollable complications, and the history of hepatitis B or C virus infection. A registration target was set at 20 patients including 5 ineligibles. Safety of deferasirox was assessed by the dose escalation methods in the individual. After the registration, deferasirox was started at a dose of 5 mg/kg for four weeks. Then, the dose was increased to 7.5 mg/kg and 10 mg/kg. The patient attended every two weeks for the safety evaluation. Cessation criteria were any grade 2 to 4 of adverse event or early disease relapse. Namely, 4 weeks medication within grade 1 of adverse events was defined as tolerable and successful medication for the identical dose. Primary endpoint was the maximum tolerate dose of deferasirox and defined from the dose in which 50 to 80% of the eligible patients were tolerable.Results: A total of 16 patients were enrolled to the study from March 2013 to January 2016. One case was excluded out of analysis due to the early relapse and 15 were eligible. Median age was 42 years old (range: 22-68). Disease included acute myeloid leukemia (n=6), acute lymphoblastic leukemia (n=2), aplastic anemia (n=2), non-Hodgkin's lymphoma (n=2), and others (n=3). Median duration from HCT to deferasirox administration was 9 months (range: 6-84). Median amount of RBC transfusions was 54 units (range: 20-156). Median value of serum ferritin was 1,537 ng/ml (range: 1,027-7,655). Regarding to the dose escalation test, 9 cases succeeded in taking from the initial 5mg/kg to the final 10mg/kg and 6 resulted in withdrawal during the treatment: abnormality of clinical test in 5 mg/kg (n=3), late relapse in 7.5 mg/kg (n=1), self-cessation and gastrointestinal event in 10 mg/kg (n=2). Achievement rates of successful medication were 80% in 5 mg/kg (12 of 15), 73% in 7.5 mg/kg (11 of 15), and 60% in10 mg/kg (9 of 15), respectively. Among 10 evaluable cases, mean value of ferritin decreased from 1,605 ng/ml at pre-treatment to 1,303 ng/ml at post-treatment. The change of other markers were as follows: hemoglobin from 12.0 g/dl to 12.6 g/dl, aspartate aminotransferase (AST) from 24.9 IU/L to 28.3 IU/L, alanine aminotransferase (ALT) from 25.8 IU/L to 28.4 IU/L, creatinine (Cr) from 0.80 mg/dl to 1.05 mg/dl. Liver iron content (LIC) was examined only in 3 cases and the mean LIC was did not change before and after the treatment at 200 μmol/g. Main of grade 1 of adverse events were elevation of clinical test including Cr (60%), AST (40%), ALT (40%), and alkaline phosphatase (33%), diarrhea (27%), abdominal pain (20%), skin rash (20%), constipation (20%), nausea (13%). None of the patients developed the exacerbation of GVHD.Conclusion: This dose escalating method of deferasirox treatment for transplant patients may be feasible. Ten mg/kg of deferasirox may be maximum tolerated dose when given after HCT. The efficacy of iron chelation would be inadequate due to the low dose and short term of deferasirox. Validation of phase 2 study is warrant. DisclosuresMorita:Bristol-Myers Squibb: Speakers Bureau. Kanda:Otsuka Pharmaceutical: Honoraria, Research Funding. Okamoto:Kyowa Hakko Kirin Co., Ltd.: Research Funding; Nippon Shinyaku Co., Ltd.: Research Funding; Bristol-Myers Squibb K.K.: Honoraria, Research Funding; Asahi Kasei Pharma Corp.: Research Funding; Shionogi & Co., Ltd.: Research Funding; Toyama Chemical Co., Ltd.: Research Funding; Chugai Pharmaceutical Co., Ltd.: Research Funding; Sumitomo Dainippon Pharma Co., Ltd.: Research Funding; Eisai Co., Ltd.: Research Funding; Teijin Pharma Limited: Research Funding; Astellas Pharma Inc.: Research Funding; Alexion Pharmaceuticals, Inc.: Research Funding; Otsuka Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Pfizer Inc.: Honoraria, Research Funding; JCR Pharmaceuticals Co., Ltd.: Research Funding.