Relative response of patients with myelodysplastic syndromes and other transfusion‐dependent anaemias to deferasirox (ICL670): a 1‐yr prospective study

Porter, John B.; Galanello, Renzo; Saglio, Giuseppe; Neufeld, Ellis E.J.; Vichinsky, Elliott; Cappellini, Maria Domenica; Olivieri, Nancy F.; Piga, Antonio; Cunningham, Melody M.J.; Soulières, Denis; Gattermann, Norbert; Tchernia, G; Maertens, Johan; Giardina, Patricia J.; Kwiatkowski, Janet L.; Quarta, Giovanni; Jeng, Michael; Forni, Gian Luca; Stadler, Michael; Cario, Holger; Debusscher, L; Porta, Matteo Della; Cazzola, Mario; Greenberg, Peter L.; Alimena, Giuliana; Rabault, B.; Gathmann, Insa; Ford, John M.; Alberti, Daniele; Rosé, Christian

doi:10.1111/j.1600-0609.2007.00985.x

Cited by 236 publications

(270 citation statements)

References 19 publications

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“…The most frequent adverse events with suspected relationship to repeated administration of deferasirox consisted of transient WHO grades I-II gastrointestinal symptoms such as nausea and diarrhea, similarly found in other studies [18,21,39,40]. These common side effects may be partly caused by the presence of lactose in the formulation of deferasirox [33] and did not require treatment discontinuation in our patients.…”

Section: Discussionsupporting

confidence: 86%

Deferasirox in MDS patients with transfusion-caused iron overload—a phase-II study

et al. 2008

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International audienceBlood transfusions represent a main component of supportive care in myelodysplastic syndromes (MDS). To avoid organ damage caused by transfusion-dependent iron overload, an adequate iron chelation therapy is required. Recently, a new oral iron chelator deferasirox (ICL670, Exjade®) has become available. A study was conducted to demonstrate the efficacy and tolerability of deferasirox in transfusion-dependent iron-overloaded patients with MDS. The efficacy of deferasirox was monitored by changes in serum ferritin, bone marrow iron, and liver iron concentration (LIC), as determined by T2*-weighted magnetic resonance imaging. Twelve patients with MDS of different subtypes (median age 76 years, range 53–91) were enrolled. Deferasirox administered in a once-daily dose of 20–30 mg/kg for 12 months was effective in reducing median ferritin concentration from 1,515 µg/L (range 665–6,900) to 413 µg/L (range 105–3,052). Within the first 4 weeks of treatment before the continuous decline of ferritin levels, the values markedly rose in eight of 12 patients. The median LIC declined from 315 to 230 µmol/g ( = 0.02) at the end of study, accompanied by a reduction of bone marrow siderosis. The most common adverse events were mild and transient gastrointestinal disturbances, skin rash, nonprogressive transient increases in serum creatinine and urine β2-microglobulin, and a temporary reduction of the creatinine clearance. The renal parameters normalized after end of treatment. No hematologic toxicities were observed. Deferasirox proved to be effective in transfusion-dependent iron overload in MDS by mobilizing iron deposits in liver and at least stabilizing iron stores in bone marrow

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Section: Discussionsupporting

confidence: 86%

Deferasirox in MDS patients with transfusion-caused iron overload—a phase-II study

et al. 2008

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“…This is similar to the data reported by Vallejo et al 30 As expected, the most frequent deferasirox-related AEs in this trial were similar to what is already known. [22][23][24]27,45,46 In the EPIC (European Prospective Investigation into Cancer and Nutrition) trial for MDS, AEs were responsible for a discontinuation rate of 23%, many of which were renal or GI events (overall discontinuation rate 49%). 22,24 Further, deferasirox treatment is envisaged to be difficult after HSCT as GI, liver and skin AEs could mimic and/or exacerbate GvHD-associated abnormalities.…”

Section: Discussionmentioning

confidence: 99%

“…[22][23][24][25][26][27][28] However, data regarding the use of deferasirox after allogeneic HSCT are limited. 15,17,19,20 This prospective multicenter trial is, to the best of our knowledge, the largest trial evaluating the efficacy and safety of deferasirox after allogeneic HSCT.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of deferasirox in non-thalassemic patients with elevated ferritin levels after allogeneic hematopoietic stem cell transplantation

Jaekel

Lieder

Albrecht

et al. 2015

Bone Marrow Transplant

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Elevated serum ferritin contributes to treatment-related morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The multicenter DE02 trial assessed the safety, efficacy and impact of deferasirox on iron homeostasis after allogeneic HSCT. Deferasirox was administered at a starting dose of 10 mg/kg per day to 76 recipients of allogeneic HSCT, with subsequent dose adjustments based on efficacy and safety. Deferasirox was initiated at a median of 168 days after HSCT, with 84% of patients still on immunosuppression. Baseline serum ferritin declined from 2045 to 957 ng/mL. Deferasirox induced a negative iron balance in 84% of patients. Hemoglobin increased in the first 3 months, and trough serum cyclosporine levels were stable. Median exposure was 330 days, with a median compliance rate of 480%. The most common investigator-reported drug-related adverse events (AEs) were increased blood creatinine (26.5%), nausea (9.0%) and abdominal discomfort (8.3%). Fifty-four (71.1%) patients experienced drug-related AEs, which occasionally resulted in discontinuation (gastrointestinal (n = 6), skin (n = 3), elevated transaminases (n = 1) and creatinine (n = 1)). The incidence of AEs appeared to be dose related, with 7.5 mg/kg per day being the best-tolerated dose. Low-dose deferasirox is an effective chelation therapy after allogeneic HSCT, with a manageable safety profile, even in patients receiving cyclosporine.

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“…[2][3][4][5][6] The once-daily oral deferasirox dispersible tablet (DT) formulation (Exjade ® ), available since 2005, offered an improved option over parenteral deferoxamine (Desferal ® ), providing greater compliance, patient satisfaction, and health-related quality of life. 7,8 The efficacy and safety of deferasirox DT has been well-defined through an extensive clinical trial program in adult and pediatric patients with a variety of anemias, including thalassemia, myelodysplastic syndromes (MDS), sickle-cell disease, and other rare anemias, [9][10][11][12][13] and has been used in clinical practice worldwide for over a decade. Nonetheless, barriers to optimal patient acceptance of treatment still exist with deferasirox DT, including palatability, the need to take the drug in a fasting state (ie, not being able to take with food), and drug-related side effects, notably gastrointestinal (GI) tolerability.…”

Section: Introductionmentioning

confidence: 99%

New film‐coated tablet formulation of deferasirox is well tolerated in patients with thalassemia or lower‐risk MDS: Results of the randomized, phase II ECLIPSE study

et al. 2017

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Once-daily deferasirox dispersible tablets (DT) have a well-defined safety and efficacy profile and, compared with parenteral deferoxamine, provide greater patient adherence, satisfaction, and quality of life. However, barriers still exist to optimal adherence, including gastrointestinal tolerability and palatability, leading to development of a new film-coated tablet (FCT) formulation that can be swallowed with a light meal, without the need to disperse into a suspension prior to consumption.The randomized, open-label, phase II ECLIPSE study evaluated the safety of deferasirox DT and FCT formulations over 24 weeks in chelation-naïve or pre-treated patients aged 10 years, with transfusion-dependent thalassemia or IPSS-R very-low-, low-, or intermediate-risk myelodysplastic syndromes. One hundred seventy-three patients were randomized 1:1 to DT (n 5 86) or FCT (n 5 87). Adverse events (overall), consistent with the known deferasirox safety profile, were reported in similar proportions of patients for each formulation (DT 89.5%; FCT 89.7%), with a lower frequency of severe events observed in patients receiving FCT (19.5% vs. 25.6% DT). Laboratory parameters (serum creatinine, creatinine clearance, alanine aminotransferase, aspartate aminotransferase and urine protein/creatinine ratio) generally remained stable throughout the study.Patient-reported outcomes showed greater adherence and satisfaction, better palatability and fewer concerns with FCT than DT. Treatment compliance by pill count was higher with FCT (92.9%) than with DT (85.3%). This analysis suggests deferasirox FCT offers an improved formulation with enhanced patient satisfaction, which may improve adherence, thereby reducing frequency and severity of iron overload-related complications. | I N T R O D U C T I O NTransfusion and iron chelation therapy can be a lifelong requirement for many patients with transfusion-dependent anemias. Compliance with iron chelation therapy can influence the frequency and severity of iron overload-related complications, 1 with demonstrated improvement in organ dysfunction and survival in patients compliant with iron chelation therapy. [2][3][4][5][6] The once-daily oral deferasirox dispersible tablet (DT) This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. variety of anemias, including thalassemia, myelodysplastic syndromes (MDS), sickle-cell disease, and other rare anemias, 9-13 and has been used in clinical practice worldwide for over a decade. Nonetheless, barriers to optimal patient acceptance of treatment still exist with deferasirox DT, including palatability, the need to take the drug in a fasting state (ie, not being able to take with food), and drug-related side effects, notably gastrointestinal (GI) tolerability. 14 An improved filmcoated tablet (FCT) formulation of deferasirox (US, Jadenu ® ; EU, Exja...

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Relative response of patients with myelodysplastic syndromes and other transfusion‐dependent anaemias to deferasirox (ICL670): a 1‐yr prospective study

Cited by 236 publications

References 19 publications

Deferasirox in MDS patients with transfusion-caused iron overload—a phase-II study

Deferasirox in MDS patients with transfusion-caused iron overload—a phase-II study

Efficacy and safety of deferasirox in non-thalassemic patients with elevated ferritin levels after allogeneic hematopoietic stem cell transplantation

New film‐coated tablet formulation of deferasirox is well tolerated in patients with thalassemia or lower‐risk MDS: Results of the randomized, phase II ECLIPSE study

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