Patient Characteristics, Treatment Patterns, and Health Outcomes in a Real-World Population of Patients with Myelofibrosis Treated with Fedratinib
Bibliographic record
Abstract
Introduction: Myelofibrosis (MF) is a type of myeloproliferative neoplasm characterized by bone marrow fibrosis, splenomegaly, progressive anemia, and debilitating constitutional symptoms. Fedratinib (FEDR) is a selective Janus kinase-2 inhibitor (JAK2i) approved for the treatment of adult patients with intermediate (int)-2 or high-risk primary or secondary MF. Patients with MF have a median overall survival of 5-7 years; however, prior to FEDR approval, ruxolitinib (RUX) was the only approved JAK2i for MF treatment, with the majority of patients discontinuing RUX within 3 years of treatment initiation (Harrison C, et al. Ann Hematol 2020;99:1177-1191). Given the current availability and use of FEDR, the primary study objective was to describe demographics, clinical characteristics, and treatment patterns of patients with MF receiving FEDR in real-world practice settings after prior RUX treatment. A secondary objective was to assess changes in MF-related symptoms and spleen size during FEDR treatment. Methods: We report interim data from a medical records review of adult patients with MF who received FEDR treatment after RUX discontinuation (due to treatment refractoriness, relapse, or intolerance) in Canada (CAN), Germany (GER), and the United Kingdom (UK). Data collection is ongoing, and we present data abstracted from March through May 2023. Patients were required to have an int-2 or high-risk MF diagnosis at FEDR initiation and to have initiated FEDR after date of first availability in each country (CAN: Sep 21, 2020, GER: Feb 9, 2021, UK: Nov 1, 2021) up to 6 months prior to data abstraction. Patients who received allogenic, hematopoietic cell transplantation after initial MF diagnosis or participated in a JAK2i trial were excluded. Spleen size evaluation through palpation at FEDR initiation and at least once within the first 6 months of FEDR use was required. Study outcomes measured were patient characteristics, treatment patterns, MF-related symptoms, and spleen size evaluations. Descriptive statistics are reported. Results: A total of 58 patients (CAN: 13, GER: 32, UK: 13) were included in the analysis. Median age at MF diagnosis and FEDR initiation was 67.9 and 71.8 years, respectively. 65.5% of patients were male, and 91.4% were White. Most patients were diagnosed with primary MF (60.3%) and had JAK2 V617F mutation (84.5%). Among patients who had a bone marrow biopsy (n = 51), 58.8% had grade 2 bone marrow fibrosis. Mean baseline Charlson Comorbidity Index score was 2.5. Median time from MF diagnosis and RUX treatment discontinuation to FEDR initiation was 34.0 months and 0.7 months, respectively. Most common reasons for FEDR initiation were splenomegaly (75.9%), RUX failure (67.2%), and to achieve symptom control (63.8%) (Table). Over a median follow-up of 12.1 months after FEDR initiation, 19 patients (32.7%) discontinued FEDR treatment with a median treatment duration of 7.7 months. Among the 39 patients taking FEDR at data abstraction, median treatment duration was 12.5 months. At FEDR initiation, 48.3% and 51.7% had int-2 risk and high-risk MF, respectively. The most common MF-related symptoms presented were fatigue (74.1%), abdominal discomfort (63.8%), and night sweats (46.6%) (Table). 62.1% of patients initiated FEDR treatment at the recommended therapeutic dose of 400 mg, and 74.1% were receiving 400 mg at end of follow-up/treatment discontinuation. Among patients with ≥ 1 FEDR dose change, titration to therapeutic dose (68.4%) was the most common reason for their first dose change. MF-related symptoms decreased in the first 6 months of FEDR treatment, including fatigue (74.1% [at FEDR initiation] reduced to 52.8% [at 6 months after FEDR initiation]), abdominal discomfort (63.8% reduced to 11.3%), and night sweats (46.6% reduced to 3.8%). The proportion of patients with severe (palpable spleen:> 20 cm) and moderate splenomegaly (palpable spleen: 11-20 cm) decreased from FEDR initiation to 6 months after initiation (severe splenomegaly: 32.8% to 7.5%, moderate splenomegaly: 55.2% to 15.1%) (Figure). Conclusion: Thepatients included in this study exhibited a significant level of illness . In this interim analysis, patients treated with FEDR following RUX treatment failure showed resolution of MF-related symptoms and a marked decrease in splenomegaly in the initial 6-month period, demonstrating the real-world effectiveness of FEDR treatment in patients with MF.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".