Efficacy and safety of deferasirox in non-thalassemic patients with elevated ferritin levels after allogeneic hematopoietic stem cell transplantation

Abstract

Elevated serum ferritin contributes to treatment-related morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The multicenter DE02 trial assessed the safety, efficacy and impact of deferasirox on iron homeostasis after allogeneic HSCT. Deferasirox was administered at a starting dose of 10 mg/kg per day to 76 recipients of allogeneic HSCT, with subsequent dose adjustments based on efficacy and safety. Deferasirox was initiated at a median of 168 days after HSCT, with 84% of patients still on immunosuppression. Baseline serum ferritin declined from 2045 to 957 ng/mL. Deferasirox induced a negative iron balance in 84% of patients. Hemoglobin increased in the first 3 months, and trough serum cyclosporine levels were stable. Median exposure was 330 days, with a median compliance rate of 480%. The most common investigator-reported drug-related adverse events (AEs) were increased blood creatinine (26.5%), nausea (9.0%) and abdominal discomfort (8.3%). Fifty-four (71.1%) patients experienced drug-related AEs, which occasionally resulted in discontinuation (gastrointestinal (n = 6), skin (n = 3), elevated transaminases (n = 1) and creatinine (n = 1)). The incidence of AEs appeared to be dose related, with 7.5 mg/kg per day being the best-tolerated dose. Low-dose deferasirox is an effective chelation therapy after allogeneic HSCT, with a manageable safety profile, even in patients receiving cyclosporine.

Phase IV open-label study of the efficacy and safety of deferasirox after allogeneic stem cell transplantation

“…1,4,5,27 In this report, the increases in serum creatinine were all below 2 times ULN. Patients taking cyclosporine did not have a higher incidence of increased serum creatinine compared with patients who did not receive cyclosporine.…”

“…1-6, [26][27][28][29][30] Two studies in patients with thalassemia (one conducted in children) reported no significant difference in post-treatment serum ferritin levels following deferasirox versus phlebotomy.…”

“…4,27 In one study, the mean dose of deferasirox at the last dose was 11 mg/kg/day in the patients with LIC of 7 mg Fe/g dw or below and 18.1 mg/kg/day in those with LIC over 7 mg Fe/ g dw. 1 In our study, the change in median serum ferritin was not significant in 3 patients who continued to require packed red blood cell transfusions during the study, implying that this subgroup of patients needed higher doses of deferasirox or more time under treatment to show a significant decrease in serum ferritin.…”

“…1-6, [26][27][28][29][30] The most frequent drug-related AEs were increased creatinine levels, increased transaminases, and gastrointestinal symptoms, which were generally mild to moderate in severity. 1,4,5,27 In this report, the increases in serum creatinine were all below 2 times ULN.…”

Current Review of Iron Overload and Related Complications in Hematopoietic Stem Cell Transplantation

“…In a recent study of 76 nonthalassemic patients, the authors reported a deferasirox-induced negative iron balance in 84% of patients after initiating it at a median of 168 days after HSCT. The drug-related adverse events were increased blood creatinine (26%), nausea (9%), and abdominal discomfort (8%) [71]. …”