Occult Iron Deficiency Might Be An Important Factor In Mpn Patients With Myeloproliferative Neoplasms (Mpn) Treated With Ruxolitinib. A Single Centre Experience

Myelofibrosis (MF) is manifested as primary myelofibrosis or post-essential thrombocythemia myelofibrosis (PET-MF), or post-polycythemia vera myelofibrosis (PPVMF). The JAK2 V617F a gain of function somatic mutation is present in approximately 50% of patients (pts) with MF. This and related mutations result in an exaggerated JAK2 signaling and they are the mechanistic cause of Ph(-) myeloproliferative neoplasms (MPN). Ruxolitinib, an oral JAK inhibitor was approved by FDA and EMEA as treatment of myelofibrosis in 201. Clinical trials have demonstrated its effectiveness and that the response rate its independent of the JAK2 mutation status or MPN subtype, , being anemia and thrombocytopenia the most common adverse events that rarely lead to drug discontinuation. In phase I/II clinical trials, in pts who were transfusion independent at baseline, new onset anemia occurred in 23% and was dose dependent, up to 20% of patients required transfusions at higher doses. It was not reported whether any specific MF subtype developed more severe anemia. Hematological toxicity in the placebo-controlled COMFORT-I study revealed grade 3 or 4 anemia in 34.2% and 11.0% of those treated with ruxolitinib and only in 15.9% and 3.3% of placebo-treated patients. The frequency of severe anemia grades 3 and 4 was higher if the initial hemoglobin (Hb) was under 10g/dl. The anemia can be managed effectively with dose modifications, temporary treatment interruptions, as well as red blood cell transfusions and/or erithropoyetin administration