Clinical outcomes of patients with myelofibrosis after immediate transition to momelotinib from ruxolitinib
Bibliographic record
Abstract
Clinical outcomes of patients with myelofibrosis after immediate transition to momelotinib from ruxolitinibJanus kinase inhibitors (JAKi) such as ruxolitinib, approved for the treatment of myelofibrosis (MF), confer symptom and spleen improvements but can induce or worsen anemia and thrombocytopenia.[1][2][3][4] Although there is no consensus on the definition of JAKi treatment failure in MF, anemia and thrombocytopenia may require a reduction in JAKi dosing or discontinuation, which are associated with poor overall survival.[5][6][7] In addition, discontinuation from ruxolitinib is complicated by the potential for discontinuation syndrome characterized by acute relapse of symptoms, splenomegaly, anemia, thrombocytopenia, and risk of hemodynamic decompensation, 5,8 with approximately 40% of the cases being moderate or severe according to real-world evidence.9 Given that discontinuation rates with ruxolitinib are high (up to 89% at 3 years) and dose modifications of ruxolitinib are associated with lower survival, 10,11 we sought to examine how transitioning directly from ruxolitinib to another therapy may be beneficial to patients with MF.Here, we present data from a retrospective analysis of a phase III clinical study (ClinicalTrials.govidentifier: NCT01969838) demonstrating that patients may be better served by a timely transition from ruxolitinib to momelotinib that can help improve anemia while maintaining or improving splenic and symptom responses.Momelotinib is a potent and selective small-molecule inhibitor of JAK1, JAK2, and activin A receptor type 1 (ACVR1); the inhibition of JAK1 and JAK2 drives symptomatic and splenic benefits while the inhibition of ACVR1 promotes restoration of iron homeostasis and erythropoiesis, resulting in anemia benefits including increased hemoglobin (Hb) levels and reduced need for transfusions.[12][13][14][15][16] Notably, transfusion-independence response with momelotinib has been associated with improved overall survival.6 Three phase III clinical studies of momelotinib in MF have provided extensive experience with momelotinib administered in more than 500 patients previously treated with ruxolitinib.[12][13][14] In the SIMPLIFY-1 study, patients in the ruxolitinib-randomized group who crossed over to receive momelotinib at week 24 were immediately administered momelotinib without ruxolitinib tapering or washout.12 Here, we conducted a retrospective analysis to evaluate the clinical outcomes (i.e., dosing, spleen volume, frequency of transfusions, Hb levels, and occurrence of adverse events) of patients with MF who immediately transitioned from ruxolitinib to momelotinib in SIMPLIFY-1.In SIMPLIFY-1, JAKi-naïve intermediate-and high-risk pa-
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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 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".