Deferasirox therapy is associated with reduced mortality risk in a medicare population with myelodysplastic syndromes

Abstract

Aims: Iron overload adversely affects patients with myelodysplastic syndromes (MDS), but benefits of iron chelation therapy have not been clearly demonstrated. We examined the association between deferasirox (DFX) therapy and mortality in transfusion-receiving Medicare patients. Patients & methods: MDS patients from 2005 to 2008 were identified using ICD-9 codes from 100% Medicare claims. Patients receiving ≥20 blood units were observed until death or end of study. Marginal structural models were used for estimation. Results: 3926 patients (10.1% used DFX) were observed for a mean of 48.8 weeks. Each incremental week of DFX was associated with a significant reduction in mortality risk (hazard ratio [HR]: 0.989; 95% CI: 0.983-0.996; p = 0.001). Conclusion: DFX therapy is associated with a reduced mortality risk among older MDS patients who received a minimum transfusion threshold.

Iron overload in myelodysplastic syndromes (MDS)

“…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].…”

Overall survival in lower IPSS risk MDS by receipt of iron chelation therapy, adjusting for patient‐related factors and measuring from time of first red blood cell transfusion dependence: an MDS‐CAN analysis

“…Although analyses suggest clinical benefit of iron overload reduction in lower risk MDS(Leitch et al, 2008;Rose et al, 2010;Cilloni et al, 2011;Komrokji et al, 2011;Delforge et al, 2012;Gattermann et al, 2012;List et al, 2012;Neukirchen et al, 2012;Remacha et al, 2012;Lyons et al, 2013;Nolte et al, 2013;Angelucci et al, 2014;Mainous et al, 2014;Zeidan et al, 2015) Although analyses suggest clinical benefit of iron overload reduction in lower risk MDS(Leitch et al, 2008;Rose et al, 2010;Cilloni et al, 2011;Komrokji et al, 2011;Delforge et al, 2012;Gattermann et al, 2012;List et al, 2012;Neukirchen et al, 2012;Remacha et al, 2012;Lyons et al, 2013;Nolte et al, 2013;Angelucci et al, 2014;Mainous et al, 2014;Zeidan et al, 2015)…”

“…Multiple analyses of iron overload reduction using iron chelation therapy (ICT) in lower risk MDS have documented an association between receiving ICT and superior OS compared to patients not receiving ICT (Leitch et al, 2008;Rose et al, 2010;Komrokji et al, 2011;Delforge et al, 2012;Neukirchen et al, 2012;Remacha et al, 2012;Lyons et al, 2014;Zeidan et al, 2015;Langemeijer et al, 2016). These studies include a matched pair analysis (Neukirchen et al, 2012), and results include an association between duration of ICT (Zeidan et al, 2015), dose of ICT (Rose et al, 2010;Langemeijer et al, 2016) and effectiveness of ICT (Neukirchen et al, 2012) and superior survival.…”

“…Multiple analyses of iron overload reduction using iron chelation therapy (ICT) in lower risk MDS have documented an association between receiving ICT and superior OS compared to patients not receiving ICT (Leitch et al, 2008;Rose et al, 2010;Komrokji et al, 2011;Delforge et al, 2012;Neukirchen et al, 2012;Remacha et al, 2012;Lyons et al, 2014;Zeidan et al, 2015;Langemeijer et al, 2016). These studies include a matched pair analysis (Neukirchen et al, 2012), and results include an association between duration of ICT (Zeidan et al, 2015), dose of ICT (Rose et al, 2010;Langemeijer et al, 2016) and effectiveness of ICT (Neukirchen et al, 2012) and superior survival. In conjunction with pre-clinical data demonstrating the toxic effects of excess iron at a cellular level (Oudit et al, 2003;Cabantchik et al, 2005;Chan et al, 2008;Kohgo et al, 2008;Kikuchi et al, 2012;Hartmann et al, 2013) and clinical data showing haematological improvement, including achieving RBC transfusion independence, in up to 20% of patients receiving ICT (Cilloni et al, 2011;Gattermann et al, 2012;List et al, 2012;Nolte et al, 2013;Angelucci et al, 2014), the data are persuasive that iron overload reduction in patients with MDS may confer clinical benefit.…”

Anticoagulation, ferrotoxicity and the future of translational lung cancer research

“…Aberrant tumor cell iron handling is central to its toxicity (43,44). Studies underway should clarify effects of iron in experimental (45)(46)(47) and human (48)(49)(50) malignancy. Little information is available on effects of iron reduction on blood coagulation.…”