Deferiprone for transfusional iron overload in sickle cell disease and other anemias: open-label study of up to 3 years

Abstract

Long-term safety and efficacy data on the iron chelator deferiprone in sickle cell disease (SCD) and other anemias are limited. FIRST-EXT was a 2-year extension study of FIRST (Ferriprox in Patients With Iron Overload in Sickle Cell Disease Trial), a 1-year, randomized noninferiority study of deferiprone vs deferoxamine in these populations. Patients who entered FIRST-EXT continued to receive, or were switched to, deferiprone. Altogether, 134 patients were enrolled in FIRST-EXT (mean age: 16.2 years), with mean (SD) exposure to deferiprone of 2.1 (0.8) years over the 2 studies. The primary end point was safety. Secondary end points were change in liver iron concentration (LIC), cardiac T2∗, serum ferritin (SF), and the proportion of responders (≥20% improvement in efficacy measure). The most common adverse events considered at least possibly related to deferiprone were neutropenia (9.0%) and abdominal pain (7.5%). LIC (mg/g dry weight) decreased over time, with mean (SD) changes from baseline at each time point (year 1, -2.64 [4.64]; year 2, -3.91 [6.38]; year 3, -6.64 [7.72], all P < .0001). Mean SF levels (μg/L) decreased significantly after year 2 (-771, P = .0008) and year 3 (-1016, P = .0420). Responder rates for LIC and SF increased each year (LIC: year 1, 46.5%; year 2, 57.1%; year 3, 66.1%; SF: year 1, 35.2%; year 2, 55.2%; year 3, 70.9%). Cardiac T2∗ remained normal in all patients. In conclusion, long-term therapy with deferiprone was not associated with new safety concerns and led to continued and progressive reduction in iron load in individuals with SCD or other anemias. The trial was registered at www.clinicaltrials.gov as #NCT02443545.

Conflict of interest statement

Conflict-of-interest disclosure: M.H. has received speaker’s fees and honoraria for advisory board participation from ApoPharma, Amgen, Bayer, Novartis, Novo Nordisk, Roche, and Takeda. A.A.M.A. has received research funding from ApoPharma. J.K. has received honoraria for consulting and advisory board participation from Fulcrum Tx, Guidepoint Global, GLG Pharma, Imara, Novartis, Graphite, Axcella Health, Sanofi, Beam, Forma, and AstraZeneca, and research funding from the National Heart Lung and Blood Institute and the Health Resources and Services Administration. J.L.K. has received consultancy fees from bluebird bio and Imara, advisory board fees from Celgene (Bristol Myers Squibb), Chiesi, Silence Therapeutics, and Agios, and research funding from ApoPharma, Novartis, bluebird bio, Sangamo, Bioverativ, and Terumo BCT. D.L., C.F., A.R., N.T.T., and F.T. are employees of Chiesi Canada Corp, the sponsor of the study. The remaining authors declare no competing financial interests.

© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Figures

Graphical abstract

Figure 1.

Participant flow. FIRST, Ferriprox in Patients with Iron Overload in Sickle Cell Disease Trial; ITT, intent-to-treat; SCD, sickle cell disease.

Figure 2.

LIC since the start of deferiprone treatment (ITT population).aOnly patients who received deferiprone in FIRST and continued deferiprone in FIRST-EXT. bOne-sample t test. dw, dry weight; ITT, intent-to-treat; LIC, liver iron concentration; max, maximum; min, minimum; SD, standard deviation.

Figure 3.

Proportion of responders and change in SF since the start of deferiprone treatment (ITT population). A responder was defined as a patient who showed a ≥20% decline from baseline in SF. Mean (SD) SF at baseline was 3894 (2591) μg/L. aOnly patients who received deferiprone in FIRST and continued deferiprone in FIRST-EXT. bOne-sample t test. max, maximum; min, minimum; ITT, intent-to-treat; SF, serum ferritin; SD, standard deviation.