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Earlier Initiation of Fedratinib May Improve Clinical Profile in Patients with Myelofibrosis Previously Treated with Ruxolitinib

Conference Correspondent

Long-term ruxolitinib (RUX) therapy often results in loss of clinical benefit and intolerance for many patients. Fedratinib (FEDR), a selective JAK2 inhibitor, was recently approved in multiple countries, including the United States, Canada, European Union, and the United Kingdom, as first-line therapy for intermediate- or high-risk myelofibrosis (MF) in patients previously treated with RUX. To date, no real-world data have been reported on demographics, clinical characteristics, and treatment patterns of FEDR therapy in patients after RUX discontinuation.

Of 150 eligible patients with a median age at diagnosis of 68 years (range, 60-74 years), 85% had primary MF, 55% were JAK2 V617F positive, and 9% were JAK2/MPL/CALR negative. Recurrent somatic mutations in the JAK2, MPL, and CALR genes have been described in patients diagnosed with myeloproliferative neoplasms. JAK2 mutations can be observed in approximately 95% of patients with polycythemia vera and essential thrombocythemia and primary MF patients typically present with mutations in JAK2/MPL/CALR. All patients were diagnosed with intermediate- or high-risk MF, had discontinued RUX therapy, and initiated FEDR treatment on or after its FDA approval date.

RUX therapy was initiated at a dose of ≥20 mg twice a day. Patients had a median platelet count of 118 × 109/L, 65% had Eastern Cooperative Oncology Group performance status 0-1, and 90% had palpable spleen. Overall median duration of RUX therapy was 7.6 months (range, 4.1-5.2 months) among all patients. Modifications in the RUX treatment regimen were observed due to various symptoms. Overall, 37% of patients experienced an adverse event while receiving RUX, and therapy was discontinued in 70% of patients due to disease progression. Other reasons for discontinuation were refractory or suboptimal response (25%) and intolerance (5%). Dose reductions were reported in 19 patients, primarily due to neutropenia (7/19) and thrombocytopenia (6/19). Treatment interruptions occurred in 4 patients due to cytopenia (2 thrombocytopenia, 1 neutropenia) and 1 patient request. Dose increases were necessary in 18 patients due to titration to therapeutic dose (13/18) and persistent MF symptoms (5/18). Median duration of therapy was shorter in patients who were refractory to or intolerant of RUX (4 months; range, 3.0-6.1 months) compared with patients with disease progression (11.7 months; range, 6.5-17.1 months).

International Prognostic Scoring System (IPSS)/Dynamic IPSS indicated 43.3% of patients had high risk, 36.7% had intermediate-2 risk, 9.3% had intermidate-1 risk, and 10% had unknown risk at initiation of FEDR therapy (400 mg twice a day for 74% of patients). At initiation of FEDR, 88% of patients had palpable spleen and median platelet count was 98 × 109/L. The primary patient-reported symptoms during FEDR therapy were fatigue (72%), abdominal discomfort (51%), and night sweats (44%). Adjustments to FEDR treatment were needed in a small proportion of patients (6%).

The current study provides insight into the clinical profile of patients from initiation and subsequent discontinuation of RUX and initiation of FEDR therapy in a real-world setting. The data suggest that high-risk patients might benefit from discontinuing RUX and starting FEDR earlier in the disease course.

Source

  • Harrison CN, Mascarenhas J, Abraham P, et al. Real-world utilization of fedratinib for myelofibrosis post-ruxolitinib: patient characteristics, treatment patterns, and characterization of ruxolitinib failure. American Society of Hematology Annual Meeting and Exposition; December 11-14, 2021. Abstract 3059.

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