title: Deferasirox for transfusion-dependent patients with myelodysplastic syndromes: safety, efficacy, and beyond (GIMEMA MDS0306 Trial).
abstract: BACKGROUND
  In the absence of randomized, controlled trial data to support iron chelation therapy in transfusion-dependent patients with myelodysplastic syndromes (MDS), continued evidence from large prospective clinical trials evaluating the efficacy and safety of iron chelation therapy in this patient population is warranted.
  
  
  METHODS
  The safety and efficacy of deferasirox was examined in a prospective, open-label, single-arm, multicenter trial of transfusion-dependent patients with International Prognostic Scoring System low- or intermediate-1-risk MDS and evidence of transfusion-related iron overload. The effects of deferasirox therapy on hematological response and disease progression were also examined.
  
  
  RESULTS
  Of 159 participants enrolled from 37 Italian centers, 152 received ≥1 dose of deferasirox (initiated at 10-20 mg/kg/day and titrated as appropriate), and 68 completed the study. Of 84 patients who discontinued deferasirox therapy, 22 died during the trial, and 28 withdrew due to an adverse event (AE). Fourteen treatment-related grade 3 AEs occurred in 11 patients, whereas no grade 4 or 5 drug-related AEs were reported. Significant risks for dropout were a higher serum ferritin level at baseline, a higher MDS-Specific Comorbidity Index, and a shorter diagnosis-enrollment interval. Median serum ferritin level fell from 1966 ng/mL to 1475 ng/mL (P < 0.0001). The cumulative incidence of transfusion independence, adjusted for death and disease progression, was 2.6%, 12.3%, and 15.5% after 6, 9, and 12 months, respectively.
  
  
  CONCLUSIONS
  Deferasirox therapy in transfusion-dependent patients with MDS was moderately well tolerated and effectively lowered serum ferritin levels. Positive hematological responses were observed, and a subset of patients achieved transfusion independence.
authors.affiliation: Hematology and Bone Marrow Transplantation Unit, Ospedale Oncologico di Riferimento Regionale "Armando Businco", Cagliari, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Angelucci
authors.forename: Valeria
authors.initials: V
authors.lastname: Santini
authors.forename: Anna Angela
authors.initials: AA
authors.lastname: Di Tucci
authors.forename: Giulia
authors.initials: G
authors.lastname: Quaresmini
authors.forename: Carlo
authors.initials: C
authors.lastname: Finelli
authors.forename: Antonio
authors.initials: A
authors.lastname: Volpe
authors.forename: Giovanni
authors.initials: G
authors.lastname: Quarta
authors.forename: Flavia
authors.initials: F
authors.lastname: Rivellini
authors.forename: Grazia
authors.initials: G
authors.lastname: Sanpaolo
authors.forename: Daniela
authors.initials: D
authors.lastname: Cilloni
authors.forename: Flavia
authors.initials: F
authors.lastname: Salvi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Caocci
authors.forename: Alfredo
authors.initials: A
authors.lastname: Molteni
authors.forename: Daniele
authors.initials: D
authors.lastname: Vallisa
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Voso
authors.forename: Susanna
authors.initials: S
authors.lastname: Fenu
authors.forename: Lorenza
authors.initials: L
authors.lastname: Borin
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Latte
authors.forename: Giuliana
authors.initials: G
authors.lastname: Alimena
authors.forename: Sergio
authors.initials: S
authors.lastname: Storti
authors.forename: Alfonso
authors.initials: A
authors.lastname: Piciocchi
authors.forename: Paola
authors.initials: P
authors.lastname: Fazi
authors.forename: Marco
authors.initials: M
authors.lastname: Vignetti
authors.forename: Sante
authors.initials: S
authors.lastname: Tura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001565:Benzoates / Q000009:adverse effects / Q000627:therapeutic use*; D001803:Blood Transfusion; D000077588:Deferasirox; D005260:Female; D005293:Ferritins / Q000097:blood; D006801:Humans; D007502:Iron Chelating Agents / Q000009:adverse effects / Q000627:therapeutic use*; D019190:Iron Overload / Q000188:drug therapy* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000150:complications* / Q000628:therapy*; D012307:Risk Factors; D065227:Transfusion Reaction; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D005293:Ferritins; D000077588:Deferasirox
keywords: chelation therapy; deferasirox; iron chelation; iron overload; myelodysplastic syndromes; safety; serum ferritin