Deferasirox for transfusion‐dependent patients with myelodysplastic syndromes: safety, efficacy, and beyond (<scp>GIMEMA MDS</scp>0306 <scp>T</scp>rial)

Angelucci, Emanuele; Santini, Valeria; Tucci, Anna Angela Di; Quaresmini, Giulia; Finelli, Carlo; Volpe, Antonio; Quarta, Giovanni; Rivellini, Flavia; Sanpaolo, Grazia; Cilloni, Daniela; Salvi, Flavia; Caocci, Giovanni; Molteni, Alfredo; Vallisa, Daniele; Voso, Maria Teresa; Fenu, Susanna; Borin, Lorenza; Latte, Giancarlo; Alimena, Giuliana; Storti, Sergio; Piciocchi, Alfonso; Fazi, Paola; Vignetti, Marco; Tura, S

doi:10.1111/ejh.12300

Cited by 94 publications

(112 citation statements)

References 47 publications

(71 reference statements)

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“…Erythroid response rates range between 11 and 22%. Table 1 Clinical trials showing erythropoietic improvement during iron chelation therapy in patients with lower risk MDS [27][28][29][30].…”

Section: Iron Overload and Bone Marrow Functionmentioning

confidence: 99%

“…Using strict criteria for erythroid response, a prospective Italian multicenter study found that during 12 months of treatment with DFX, RBC transfusion requirement declined significantly from a median of 3 to a median of 1 RBC units per month [30]. The cumulative incidence of transfusion independence increased from 2.6% at 6 months to 15.5% at 12 months.…”

Section: Iron Overload and Bone Marrow Functionmentioning

confidence: 99%

“…List et al [27] Low/lnt-1 15% (n = 173) 15% (n = 52) 22% (n = 77) Gattermann et al [28] Low/lnt-1 21.5% (n = 247) 22% (r = 50) 13% (n = 100) Nolte et al [29] Low/lnt-1 11% (n = 50) NR NR Angelucci et al [30] Low/lnt-1 Transfusion independence in 15.5% (n = 152) Table 2 Clinical studies showing that iron chelation improves survival in patients with lower risk MDS [32][33][34][35][36][37][38][39][40].…”

Section: Is There a Survival Benefit From Chelation Therapy (Ict)?mentioning

confidence: 99%

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Iron overload in myelodysplastic syndromes (MDS)

Gattermann

2017

Int J Hematol

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Iron overload (IOL) starts to develop in MDS patients before they become transfusion-dependent because ineffective erythropoiesis suppresses hepcidin production in the liver and thus leads to unrestrained intestinal iron uptake. However, the most important cause of iron overload in MDS is chronic transfusion therapy. While transfusion dependency by itself is a negative prognostic factor reflecting poor bone marrow function, the ensuing transfusional iron overload has an additional dose-dependent negative impact on the survival of patients with lower risk MDS. Cardiac dysfunction appears to be important in this context, as a consequence of chronic anemia, age-related cardiac comorbidity, and iron overload. Another potential problem is iron-related endothelial dysfunction. There is some evidence that with increasing age, high circulating iron levels worsen the atherosclerotic phenotype. Transfusional IOL also appears to aggravate bone marrow failure in MDS, through unfavorable effects on mesenchymal stromal cells as well a hematopoietic cells, particularly erythroid precursors. Patient series and clinical trials have shown that the iron chelators deferoxamine and deferasirox can improve hematopoiesis in a minority of transfusion-dependent patients. Analyses of registry data suggest that iron chelation provides a survival benefit for patients with MDS, but data from a prospective randomized clinical trial are still lacking.

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Section: Iron Overload and Bone Marrow Functionmentioning

confidence: 99%

Section: Iron Overload and Bone Marrow Functionmentioning

confidence: 99%

Section: Is There a Survival Benefit From Chelation Therapy (Ict)?mentioning

confidence: 99%

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Iron overload in myelodysplastic syndromes (MDS)

Gattermann

2017

Int J Hematol

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“…Although mainly obtained from retrospective trials, data indicate that DFX might improve survival and reduce morbidity in such patients. Moreover, improvement of hematopoiesis during DFX treatment was reported by several groups with erythroid, neutrophil and platelet responses seen in 6-21%, 3-17%, and 15-30% of the patients, respectively, including transfusion independency for PRBC at 12 months of DFX treatment of 12% in a trial from the Italian GIMEMA group [33][34][35].…”

Section: Potential Benefits Of Iron Chelation In Transfusion Dependenmentioning

confidence: 87%

“…DFX has shown its efficacy in sufficiently reducing serum ferritin in transfusion dependent patients with MDS and IOL [30][31][32][33][34]. Although mainly obtained from retrospective trials, data indicate that DFX might improve survival and reduce morbidity in such patients.…”

Section: Potential Benefits Of Iron Chelation In Transfusion Dependenmentioning

confidence: 99%

Updated recommendations on the management of gastrointestinal disturbances during iron chelation therapy with Deferasirox in transfusion dependent patients with myelodysplastic syndrome – Emphasis on optimized dosing schedules and new formulations

Nolte¹,

Angelucci²,

Breccia³

et al. 2015

Leukemia Research

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a b s t r a c tMyelodysplastic syndromes (MDS) are oligoclonal hematopoietic disorders characterized by peripheral cytopenias with anemias being the most prevalent feature. The majority of patients will depend on regular transfusions of packed red blood cells (PRBC) during the course of the disease. Particularly patients with MDS and low risk for transformation into acute myeloid leukemia and low risk of early death will receive PRBC transfusions on a regular basis, which puts them at high risk for transfusional iron overload. Transfusion dependence has been associated with negative impact on organ function and reduced life expectancy.Recently, several retrospective but also some prospective studies have indicated, that transfusion dependent patients with MDS might benefit from consequent iron chelation with regard to morbidity and mortality. However, low treatment adherence due to adverse events mainly gastrointestinal in nature is an important obstacle in achieving sufficient iron chelation in MDS patients. Here, we will summarize and discuss the existing data on Deferasirox in low risk MDS published so far and provide recommendations for optimal management of gastrointestinal adverse events during iron chelation aiming at improving treatment compliance and, hence, sufficiently removing excess iron from the patients.

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