Prescribing information

 

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Iron overload in patients with MDS1–3

Up to 80% of patients with iron overload will develop transfusion dependency4–6

Patients can develop clinically relevant iron burden in less than one year of receiving RBC transfusions7

  • Patients developed clinically relevant iron burden (serum ferritin of 1,000 μg/L) after a median of 21 RBC units (median time from development of transfusion requirement to onset of iron overload, 10.8 months)7

Evidence in patients with MDS suggests that iron overload can impact survival outcomes8

  • Retrospective data suggests that serum ferritin might be a contributor to increased morbidity and mortality in early-stage MDS8
  • Iron overload is shown to significantly affect OS (p<0.001) in MDS patients, with a HR of 1.36 for every 500 μg/L increase in serum ferritin over 1,000 μg/L)7,9

EXJADE: Proven to reduce serum ferritin in iron-overloaded MDS patients3,10

The EPIC study was the largest investigation to-date conducted for an iron chelator, evaluating the efficacy and safety of EXJADE:3,10

  • A total of 1,744 patients participated*, of which 341 patients had MDS3,10
  • There was a significant reduction in serum ferritin from BL (–264 μg/L; p<0.0001; n=1,707) after 1 year of EXJADE treatment for all patients3,10

Median change from BL in serum ferritin3

All patients3

Graph showing the median change in serum ferritin and mean EXJADE dose in all patients from baseline to month 12

Based on a LOCF analysis, the overall median serum ferritin levels in patients with MDS who completed the 1-year study significantly decreased from BL after 1 year of EXJADE treatment (-253 μg/L; p=0.002; n=175).3

The extent of reduction in serum ferritin reflected the dosage adjustments during the study (median of 6 months after treatment initiation) and iron intake over the course of the study.10

EXJADE: May improve survival outcomes in patients with MDS vs. placebo11

The TELESTO study was the first prospective, placebo-controlled, randomised iron chelation study to evaluate the EFS and safety of EXJADE in patients with low to intermediate risk MDS.

  • Median EFS was prolonged by almost 1 year with EXJADE vs. placebo [3.9 years (95% CI: 3.2–4.3) vs. 3.0 years (95% CI: 2.2–3.7) respectively; HR: 0.64 (95% CI: 0.42–0.96)]
  • Median OS with EXJADE vs. placebo was 5.2 years (95% CI: 3.9–not estimable) vs. 4.1 years (95% CI: 3.0–4.9) respectively; HR: 0.83 (95% CI: 0.54–1.28)

Kaplan-Meier plot of EFS11‡

All patients on a dose 10–40 mg/kg/day based on dosing guidelines

Graph showing the probability of EFS with EXJADE or placebo in all patients on a dose 10–40 mg/kg/day from baseline to day 4

*1,744 patients were enrolled and had the following conditions: thalassaemia (n=1,115), MDS (n=341), aplastic anaemia (n=116), SCD (n=80), rare anaemias (n=43). Based on a Wald test from the Cox model. Kaplan–Meier curve by treatment with 95% Hall–Wellner bands.

 

Abbreviations: BL, baseline; CI, confidence interval; DT, dispersible tablets; EFS event-free survival; HR, hazard ratio; ICT, iron chelation therapy; LOCF, last-observation carried forward; MDS, myelodysplastic syndromes; OS, overall survival; RBC, red blood cell.

References

  1. EXJADE® dispersible tablets summary of product characteristics.
  2. EXJADE® film-coated tablets summary of product characteristics.
  3. Gattermann N, et al. Deferasirox in iron-overloaded patients with transfusion-dependent myelodysplastic syndromes: Results from the large 1-year EPIC study. Leuk Res 2010;1143–1150.
  4. Shenoy N, et al. Impact of iron overload and potential benefit from iron chelation in low-risk myelodysplastic syndrome. Blood. 2014;124(6):873–881.
  5. Temraz S, et al. Iron overload and chelation therapy in myelodysplastic syndromes. Crit Rev Oncol Hematol. 2014;91(1):64–73.
  6. Cermak J, et al. Impact of transfusion dependency on survival in patients with early myelodysplastic syndrome without excess of blasts. Leuk Res. 2009;33(11):1469–1474.
  7. Malcovati L, et al. Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making. J Clin Oncol. 2005 Oct 20;23(30):7594–7603.
  8. Malcovati L, et al. Impact of transfusion dependency and secondary iron overload on the survival of patients with myelodysplastic syndromes. Leuk Res. 2007;31 Suppl 3:S2–6.
  9. Mitchell M, et al. Iron chelation therapy in myelodysplastic syndromes: where do we stand? Expert Rev Hematol. 2013;6(4):397–410.
  10. Cappellini M, et al. Tailoring iron chelation by iron intake and serum ferritin: the prospective EPIC study of deferasirox in 1744 patients with transfusion-dependent anemias. Haematologica 2010;95:557–566.
  11. Angelucci E, et al. Iron chelation in transfusion-dependent patients with Low- to Intermediate-1-risk myelodysplastic syndromes: a randomized trial. Ann Intern Med. 2020 Mar. [Epub ahead of print].
HCP20-C005c June 2020.
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