P1037: CONSISTENCY OF PACRITINIB FOR SPLEEN AND SYMPTOM REDUCTION IN PATIENTS WITH MYELOFIBROSIS REGARDLESS OF CYTOPENIAS
Bibliographic record
Abstract
Topic: 16. Myeloproliferative neoplasms - Clinical Background: In patients with myelofibrosis (MF), JAK inhibitor therapy can improve both splenomegaly and disease symptoms. Unfortunately, dosing – and thus efficacy – of the available JAK1/2 inhibitors ruxolitinib and fedratinib is frequently limited in patients with cytopenic MF due to drug-induced exacerbation of cytopenias. Pacritinib is a JAK1-sparing inhibitor of JAK2/IRAK1/ACVR1 that has been studied at full dose in patients with MF regardless of cytopenias. Aims: To present data on spleen and symptom benefit in pacritinib-treated patients stratified by both baseline platelet (PLT) count and hemoglobin (HB) level. Methods: Evaluable patients treated with pacritinib (200 mg twice daily or 400 mg daily) in the PERSIST-1 and PERSIST-2 studies were analyzed, stratified by baseline PLT count (<100, ≥100x109/L) and HB level (<8, 8 to <10, ≥10 g/dL). Groups were analyzed for depth of spleen volume response (SVR), total symptom score (TSS; version 2.0 excluding tiredness) response, patient global impression of change (PGIC), and dose intensity. Results: Of 276 patients evaluable for spleen response, median age at baseline was 67 years, 51.5% had grade 3 bone marrow fibrosis, 70% had primary MF, and 16% had prior JAK2 inhibitor exposure. Median pacritinib dose intensity was >99.7% for the duration of the study across PLT and HB subgroups. Overall, 80% of patients achieved ≥10% SVR, 75.5% had ≥10% TSS reduction, and 78% reported that their symptoms were “improved” at week 24. Week 24 spleen reduction occurred consistently across PLT and HB strata (Figure 1a), with 84-93% experiencing clinical improvement (any spleen reduction) and 21-28% achieving spleen response (≥35% SVR). Spleen response occurred at similar rates regardless of baseline PLT or HB strata, with most patients achieving full benefit by Week 12 (Figure 1b). Symptom response was also consistent across strata, though TSS response (≥50% TSS reduction) occurred at highest rates (62.5%) in patients with HB <8 g/dL (Figure 1c). There was no diminution in TSS reduction in patients with thrombocytopenia compared to those with higher PLT counts. Unlike spleen reduction, symptom benefit continued to occur beyond week 12, particularly in patients with baseline HB <8 g/dL (Figure 1d). Across all analyzed cytopenia subgroups, at least three-quarters of patients (75-81%) reported symptoms were “improved” at week 24, with 37-55% reporting that their symptoms were “much” or “very much improved”. Summary/Conclusion: Pacritinib demonstrates consistent efficacy for spleen and symptom response in patients with MF regardless of blood counts. This consistent effect may be related to pacritinib’s unique kinome profile and its ability to be delivered at full dose in patients with MF regardless of cytopenias.Keywords: Spleen, Myelofibrosis, Janus Kinase inhibitor
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".