A Phase II, Multicenter, Single-Arm Study to Evaluate the Safety and Efficacy of Deferasirox after Hematopoietic Stem Cell Transplantation in Children with beta-Thalassemia Major

作者：Yesilipek Mehmet Akif^*; Karasu Gulsun; Kaya Zuhre; Kuskonmaz Baris B; Uygun Vedat; Dag Ilkiz; Ozudogru Onur; Ertem Mehmet

来源：Biology of Blood and Marrow Transplantation, 2018, 24(3): 613-618.

DOI：10.1016/j.bbmt.2017.11.006

• Iron chelation
• Iron overload
• Bone marrow transplant
• Transfusion-dependent thalassemia

We conducted a prospective, phase II, multicenter, single-arm study to evaluate the efficacy and safety of deferasirox in patients age >2 to <18 years with beta-thalassemia major (TM) who underwent hematopoietic stem cell transplantation (HSCT) and had evidence of iron overload (serum ferritin >1000 mu g/L; cardiac MRI T2* <20 ms, or liver iron concentration [LIC; by MRI R2] >= 5 mg/g). Patients received deferasirox at an initial dose of 10 mg/kg/day, with up-titration to a maximum of 20 mg/kg/day. The study continued for 52 weeks and included a total of 27 patients (mean age, 9.1 +/- 3.8 years; 70.4% male). One patient (3.7%) was lost to follow-up. The majority of patients (n = 20; 74.1%) were able to achieve the intended dose of 20 mg/kg/day. No deaths occurred. A total of 134 adverse events (AEs) were reported in 25 patients (92.6%) during the study. The majority of patients had grade 1 or 2 AEs, with only 8 patients (29.6%) experiencing grade 3 AEs. Only 10 AEs occurring in 4 patients (14.8%) were suspected to be related to deferasirox (ALT/AST increase, n = 4; urinary tract infection, n = 1). The deferasirox dose had to be adjusted or interrupted for 6 AEs occurring in 4 patients (14.8%). A total of 6 serious AEs occurred in 3 patients (11.1%), none of which were suspected to be related to deferasirox. From baseline to week 52, there were decreases in median concentrations of alanine aminotransferase (ALT), from 30.0 to 17.0 IU/L, and aspartate aminotransferase (AST), from 35.5 to 26.0 IU/L. Median serum creatinine and cystatin C concentrations were similar at baseline and week 52. There was a continuous and significant decrease in median serum ferritin level from 1718.0 mu g/L at baseline to 845.3 mu g/L following 52 weeks of therapy (P<.001); 9 patients (33.3%) achieved a level of <500 mu g/L. There was also a significant decrease in median LIC (from 8.6 to 4.1 mg/g; P<.001) and an increase in median cardiac T2* (from 26.0 to 28.0 ms; P=.520) from baseline to week 52. Our findings indicate that deferasirox treatment at doses up to 20 mg/kg/day reduces the iron burden in children with TM post-HSCT, with a manageable safety profile.

• 出版日期2018-3