Occult Iron Deficiency Might be an Important Factor in MPN Patients with Myeloproliferative Neoplasms (MPN) Treated with Ruxolitinib. a Single Centre Experience

Abstract

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 Aim: To describe hematological toxicity management on MF pts treated with ruxolitinib Methods: Descriptive, retrospective analysis addressing the anemia safety profile of five MF patients (WHO criteria) treated with ruxolitinib with a median age of 68.2 years. One patient had PMF, 3 had PPV-MF and 1 had PET-MF. One of them required transfusion support, and two of them who had documented iron deficiency, were treated with iron supplementation with marked improvement (Table 1) without requiring dose reduction. Abstract 5564. TableGenderAgeDiagnosisDate of DxDate start TxDose start TxBaseline Hb (gr/dL)Anemia (> 2 gr/dL)Time of tx until anemiaIron SupplementationTransfusion supportAnemia OutcomeFemale79PPV MF04-feb-0522-nov-1220 mg/BID14.4Yes8 weeksYesNoImprovedFemale49PET MF01-Dec-9815-Jan-1320 mg/BID16.6YesYesNoImprovedFemale79PPV-MF07-mar-9613-may-1320 mg/BID14.4NoN/AN/AN/AN/AFemale85PPV-MF01-abr-0902-sep-1315 mg/BID13.3NoN/ANoN/AN/AMale79PMF04-jul-1312-ago-1310 mg/BID8.5Yes16 weeksYesYesImproved Conclusion: Use of ruxolitinib in clinical practice requires careful monitoring of anemia, which is a common side effect that might require dose reduction or hematological support with blood transfusions and erithropoyetin. As PPVMF patients are frequently iron deficient we postulate that the identification and treatment of iron deficiency in patients with secondary myelofibrosis is an important issue as it may ameliorate the anemia, avoiding transfusions, Ruxolitinib discontinuation and therefore improving the treatment outcome. This very provocative observation warrants further investigations addressing this issue. Disclosures No relevant conflicts of interest to declare.