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The Use of Fedratinib (FEDR) for Myelofibrosis (MF) As a Potential Bridge to Hematopoietic Stem Cell Transplantation (HSCT) after Ruxolitinib (RUX) Failure: Real-World Assessment of Treatment Characteristics and Spleen, Symptoms, and Hematologic Response

Year: 2024

Type: article

Abstract: Fedratinib (FEDR), a Janus Kinase inhibitor, has been shown to provide therapeutic benefits and symptom control in patients with MF. However, there is limited evidence on the use of FEDR following failure of RUX as a treatment pathway to HSCT, the only curative option for patients with MF. Describe real-world patient characteristics, treatment characteristics, spleen/symptom changes, and outcomes following discontinuation of FEDR to undergo allogeneic HSCT, after prior treatment with RUX. Treating physicians (N=6) from community oncology practices in the US selected eligible patients and completed electronic case report forms in early 2021, then provided updates in early 2023. Eligible patients were adults with intermediate- or high-risk MF, treated with RUX and subsequently initiated FEDR on or after August 16, 2019, then discontinued FEDR for HSCT. Physicians abstracted patient characteristics and clinical outcomes. Descriptive analyses were applied. Physician-reported mean spleen and symptom changes at FEDR initiation versus 3 months post-FEDR initiation were compared via paired 2-sided t-tests. A total of 18 patients initiated FEDR as a bridge to HSCT; 61% were male. At FEDR initiation, median age was 56 years and all patients had ECOG ≤ 2. Median RUX treatment duration was 9.8 months, time from RUX failure (i.e., refractory/suboptimal response, progression, or intolerance) to discontinuation was 23 days, and from RUX failure to FEDR initiation was 38 days. The starting dose of FEDR was 400 mg once daily for 17 patients; median treatment duration was 6.9 months. Median length of follow-up from FEDR initiation was 15.2 months (Table 1). From FEDR initiation to 3 months post-FEDR treatment, there were significant reductions in mean spleen size (mean of 15.1 cm to 9.0 cm; P=0.021) and mean number of symptoms (mean of 4.9 to 2.3; P=0.009). There was a reduction in mean WBC count from FEDR initiation to 3 months post-FEDR initiation (mean of 10.2 to 6.2) and a significant increase in mean Hb level (mean of 8.2 to 9.5; P=0.002), while other hematologic parameters remained relatively stable (Table 2). Among patients who discontinued FEDR to bridge to HSCT, n=4 patients experienced transformation to blast phase myeloproliferative neoplasms (MPN) prior to undergoing HSCT. Overall, n=4 (22.2%) deaths were recorded as of May 2023. Two of the 4 deaths were related to MF and both patients had disease transformation to blast phase MPN before HSCT. A median duration of 14.5 months elapsed between FEDR initiation and death among these 4 patients. This study described characteristics and outcomes of MF patients receiving FEDR as a potential bridge to HSCT. Although data are based on a small sample size, HSCT following FEDR after RUX failure may be an effective treatment option to consider. Further research is needed to confirm its efficacy and determine safety.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.jtct.2023.12.521