P1057: REAL-WORLD UTILIZATION OF FEDRATINIB FOR MYELOFIBROSIS FOLLOWING RUXOLITINIB FAILURE

Abstract

Background: In August 2019, fedratinib (FEDR) became the second treatment, after ruxolitinib (RUX), to be approved for intermediate (Int)- or high-risk (HR) primary or secondary myelofibrosis (MF). Aims: To characterize real-world patient characteristics and treatment patterns for patients with MF receiving FEDR after RUX therapy in US clinical practices. Methods: Adults with Int- or HR MF initiating FEDR on or after August 16, 2019 (FEDR approval date) after discontinuing RUX were identified from community oncology practices. Eligible patients had ≥90 days of follow-up from FEDR initiation, completed ≥1 FEDR cycle, and had a spleen size assessment at FEDR initiation. Treating physicians completed electronic case report forms for the selected eligible patients, capturing patient characteristics at time of MF diagnosis and during RUX and FEDR therapy, including bone marrow fibrosis grade, biomarkers, risk score, performance status score, spleen size (cm above the costal margin), symptoms (per Modified Myelofibrosis Symptom Assessment Form version 4.0), and complete blood count data. Providers reported treatment dosing and modifications and dates/rationale for RUX treatment failure (defined a priori, including refractory or suboptimal response, disease progression [PD], or intolerance). Results: Among 150 eligible patients, the median age at diagnosis was 68 years; 55% were male, 68% were non-Hispanic White, 85% had primary MF, 55% were JAK2 V617F-positive, and 9% were JAK2/MPL/CALR-negative. RUX initiation dosage was ≥20 mg twice/daily (bid) for approximately 50% of patients. At RUX initiation, 65% had ECOG scores of 0/1, and 90% had palpable spleen (Table). A total of 19 patients (13%) had RUX dosage reductions due to neutropenia (7), thrombocytopenia (6), other adverse event (AE)/toxicity (3), patient request (2), and anemia (1); 4 patients (3%) had treatment interruptions due to thrombocytopenia (2), neutropenia (1), other AE/toxicity (1), and patient request (1); and 18 patients (12%) had dosage increases due to titration (13) and persistent MF symptoms (5). Primary reasons for RUX discontinuation were PD (70%), refractory or suboptimal response (25%), or intolerance (5%). RUX discontinuation due to PD was most often attributed to MF symptom return (65%), increased spleen size to >50% vs best achieved response (23%), and other reasons (12%). Median RUX duration was 4.0 months (IQR, 3.0–6.1) for refractory or intolerant patients and 11.7 months (IQR, 6.5–17.1) for those with PD. FEDR was initiated at 400 mg daily for 74% of patients. At FEDR initiation, 43% had International Prognostic Scoring System (IPSS)/Dynamic IPSS HR, 37% Int-2 risk, and 88% had palpable spleen; mean spleen size was 16.0 cm, and median platelet count was 98.0×109/L (Table). Symptoms reported at FEDR initiation included fatigue (72%), abdominal discomfort (51%), night sweats (44%), early satiety (25%), bone pain (18%), itching (13%), and pain under the left rib (13%). At the end of follow-up, 44 patients (29.3%) were deceased, and mean time to death among deceased patients was 6.5 (standard deviation, 2.7) months from initiation of FEDR. Image:Summary/Conclusion: This study showed a short duration of RUX therapy for real-world patients with MF, and poorer clinical status at FEDR initiation than at RUX initiation. Patients at risk of early failure of RUX should be considered for earlier FEDR interventional treatment.