Department of Hematology, Oncology and Clinical Immunology, Heinrich Heine University, Dusseldorf, Germany. Hospital Josep Trueta ICO Girona, Girona, Spain. Private Practice for Hematology/Oncology, Dresden, Germany. Pennine Acute Hospital, Manchester, UK. Novartis Pharma AG, Basel, Switzerland. Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA. Novartis Pharma AG, Basel, Switzerland. The First Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, Zhejiang, China.
OBJECTIVES Erythropoiesis-stimulating agents (ESAs) remain first-choice to treat symptomatic anemia and delay transfusion dependence in most patients with lower-risk myelodysplastic syndromes (MDS) without del(5q). Deferasirox increased erythroid responses in some lower-risk MDS patients in clinical trials, and adding low-dose deferasirox to ESA treatment may further improve erythroid response. METHODS KALLISTO (NCT01868477) was a randomized, open-label, multicenter, phase II study. Lower-risk
MDS patients received deferasirox at 10 mg/kg/day (dispersible tablets) or 7 mg/kg/day (film-coated tablets) plus erythropoietin (n=11), or erythropoietin alone (n=12) for 24 weeks. The primary endpoint was the between-group difference in erythroid response within 12 weeks. RESULTS Erythroid response occurred in 27.3% of patients receiving deferasirox plus erythropoietin versus 41.7% of patients receiving erythropoietin alone within 12 weeks (difference 14.4%; 95% CI -24.0, 48.16). Within 24 weeks, the hematologic response rate was 27.3% with deferasirox plus erythropoietin versus 50% with erythropoietin alone, and hematologic improvement rates were 45.5% versus 100%. Deferasirox plus erythropoietin was generally well tolerated. CONCLUSIONS In this small pilot study, combining low-dose deferasirox with erythropoietin did not improve erythroid response. It remains of interest to investigate early chelation approaches with even lower deferasirox doses plus erythropoietin in lower-risk MDS patients before the onset of transfusion dependence. KEY WORDS Deferasirox, erythropoietin, myelodysplastic syndromes, anemia, therapy, hematologic response, erythroid response, clinical trials This article is protected by copyright. All rights reserved.