Hematological Improvement during Deferasirox Treatment in Patients with Myeloproliferative Neoplasms (MPN)

Background Deferasirox (DFX) is an oral iron chelator widely employed to reduce iron overload in patients with myelodysplastic syndromes; in this subset, an unexpected hematological improvement (HI) has been reported in about 20% of cases by several groups. At present, only few case reports showed a similar HI in patients with Ph- Myeloproliferative Neoplasms (MPN) and transfusional requirement receiving DFX treatment.

Aim To address the incidence of HI during DFX treatment in MPN patients, we revised all patients with MPN and iron overload secondary to transfusional requirement enrolled in the database of our regional cooperative group who received a treatment with deferasirox.

Methods Twenty-eight patients [M/F 22/6, median age at diagnosis 68.8 years, interquartile range (IQR) 63.2 – 74.3] were reported in the database. Of them, 25 had a primary Myelofibrosis, 2 a post Essential Thrombocythemia myelofibrotic phase (MP) and 1 a post Polycythemia Vera MP. An HI was considered as a rise in Hb values ≥ 1.5 g/dl and/or a reduction in the transfusional requirement ≥ 50% lasting at least 3 months.

Results Treatment with DFX was started after a median interval from diagnosis of 12.8 months (IR 7.1 – 43.1) and from transfusion requirement of 10.0 months (IR 5.7 – 15.9). Median Hb and ferritin values at baseline were 7.8 g/dl (IQR 7.2 – 8.4) and 1,415 ng/ml (IQR 1,168 – 1768), respectively. Starting DFX dose was 1,500 mg/day in 13 patients, 1,250 mg/day in 5 patients, 1,000 mg/day in 9 patients and <1,000 mg/day in 1 patient. Extra-hematological toxicity was reported in 16/28 patients (57.1%) and a dose reduction/temporary discontinuation was needed in 12 cases (42.8%), but only 2 patient went off treatment due to toxicity. Twenty-six patients were considered evaluable for response (≥ 6 months of treatment): after a median treatment period of 15.4 months (IR 8.1 – 22.3), 11 patients (42.3%) achieved a reduction of iron overload with ferritin levels < 1,000 ng/ml. As to HI, 6/26 patients (23.0%) showed an unexpected and persistent (> 3 months) rise of Hb levels > 1.5 g/dl, with disappearance of transfusional requirement in 4 cases and reduction ≥ 50% in the remaining 2 cases. The main clinical features of these 6 patients at DFX initiation and at HI are reported in the Table.

The HI was achieved together with a reduction of ferritin levels in 4 cases, while it was independent by ferritin response in the remaining 2 cases. To identify factors predicting the achievement of HI, many features at baseline (age, gender, Hb and ferritin levels, interval from diagnosis to DFX treatment) were compared between patients obtaining or not HI: however, none of them showed a significant role.

Conclusions Treatment with DFX is feasible and effective in MPN with iron overload. Moreover, it is worth of note and deserves further biological and clinical insights that also in this setting an hematological improvement can occur in a sizeable rate of patients.