Iron‐chelating therapy with deferasirox in transfusion‐dependent, higher risk myelodysplastic syndromes: a retrospective, multicentre study

Abstract

Iron chelation is controversial in higher risk myelodysplastic syndromes (HR-MDS), outside the allogeneic transplant setting. We conducted a retrospective, multicentre study in 51 patients with transfusion-dependent, intermediate-to-very high risk MDS, according to the revised international prognostic scoring system, treated with the oral iron chelating agent deferasirox (DFX). Thirty-six patients (71%) received azacitidine concomitantly. DFX was given at a median dose of 1000 mg/day (range 375-2500 mg) for a median of 11 months (range 0·4-75). Eight patients (16%) showed grade 2-3 toxicities (renal or gastrointestinal), 4 of whom (8%) required drug interruption. Median ferritin levels decreased from 1709 μg/l at baseline to 1100 μg/l after 12 months of treatment (P = 0·02). Seventeen patients showed abnormal transaminase levels at baseline, which improved or normalized under DFX treatment in eight cases. One patient showed a remarkable haematological improvement. At a median follow up of 35·3 months, median overall survival was 37·5 months. The results of this first survey of DFX in HR-MDS are comparable, in terms of safety and efficacy, with those observed in lower-risk MDS. Though larger, prospective studies are required to demonstrate real clinical benefits, our data suggest that DFX is feasible and might be considered in a selected cohort of HR-MDS patients.

Sustained Erythroid Response in a Patient with Myelofibrosis Receiving Concomitant Treatment with Ruxolitinib and Deferasirox

“…Prospective well-designed trials of deferasirox in MF should provide information on the frequency and magnitude of such an effect and examine the potential impact of therapy on other relevant outcomes in MF, such as overall survival, marrow fibrosis, and quality of life [19]. …”

Systematic Literature Review of Treatment Options and Clinical Outcomes for Patients With Higher-Risk Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia

“…Data on the 18 HR-MDS trials are shown in Table 2. 3,[13][14][15][16][18][19][20][21][22][23][26][27][28][29][30][32][33][34] Chemotherapy: Conventional Chemotherapy Regimens Overall, the prognosis of patients treated with CCRs in realworld settings was poor, particularly with respect to longer-term OS. Among patients receiving CCRs, 2 studies, Bernal et al 13 and Kantarjian et al 23 reported median OS of 12.2 and 34 weeks (3 and 8.5 months), respectively.…”

“…The study reported by Musto et al 29 One study (Kantarjian et al 22 ) reported survival for patients who underwent allo-HSCT after chemotherapy (cytarabine with or without topotecan with or without cyclophosphamides, or fludarabine with or without anthracyclines); those who had the procedure while experiencing a first CR had a higher estimated 5-year survival rate (36%) than those who underwent the procedure after a first CR failed (9%).…”

“…Four studies in HR-MDS reported rates of allo-HSCT ranging from 6% to 14%. 18,22,29,33 Despite the fact that populations and previous treatments received were variable across studies, rates of allo-HSCT after therapy were fairly consistent. The study reporting the lowest rate examined patients treated with azacitidine who underwent allo-HSCT before their third treatment cycle 18 ; additionally, only 22% of patients in this study were classified as high-risk according to IPSS.…”

Prospective evaluation of the effect of deferasirox on hematologic response in transfusion‐dependent patients with low‐risk MDS and iron overload

“…Although time to hematologic improvement observed in our study was particularly late (6 months and 10 months for HI-N and HI-P, respectively), it has to be noted that, although more rarely, hematologic improvement may occur early, 11 even in the setting of higher risk patients. 14 have also to be considered according to previous studies. 27,28 Our work shows some discrepancies in results at 3 months when based on transfusion requirement assessed over a 8-week period compared to IWG criteria for minor erythroid response.…”