Consistency of pacritinib for spleen and symptom reduction in patients with myelofibrosis regardless of cytopenias.
Bibliographic record
Abstract
7068 Background: In patients with myelofibrosis (MF), JAK inhibitor therapy can improve both splenomegaly and disease symptoms. Unfortunately, dosing – and thus efficacy – of available current JAK1/2 inhibitors is frequently limited in patients with cytopenic MF due to drug-induced exacerbation of cytopenias. Pacritinib is a novel JAK1-sparing inhibitor of JAK2/IRAK1/ACVR1 that has been studied at full dose in patients with MF regardless of cytopenias. Here, we present data on spleen and symptom benefit in pacritinib-treated patients across the cytopenic spectrum, stratified by both baseline platelet (PLT) count and hemoglobin (HB) level. Methods: Evaluable patients treated with pacritinib in the PERSIST-1 and PERSIST-2 studies were analyzed, stratified by baseline PLT (<100, ≥100x109/L) and HB (<8, 8 to <10, ≥10 g/dL). Groups were analyzed for depth of spleen volume response (SVR), modified total symptom score (TSS) response, patient global impression of change (PGIC), and dose intensity. Results: Of 276 patients evaluable for spleen response, median age was 67 years, 51.5% had grade 3 fibrosis, 70% had primary MF, and 16% had prior JAK2 inhibitor exposure. Median dose intensity was >99.7% for the duration of the study across PLT and HB subgroups. Overall, 80% of patients had ≥10% SVR (SVR-10), 75.5% had TSS-10, and 78% reported that their symptoms were improved at week 24. Week 24 spleen reduction occurred consistently across PLT and HB strata, with 84-93% and 86-90% of patients respectively (Table). SVR-35 occurred in 23-25% of patients across PLT strata and in 21-28% of patients across HB strata. Symptom response was also consistent across strata, though TSS-50 occurred at highest rates (62.5%) in patients with HB <8 g/dL. There was no diminution in symptom burden reduction in patients with thrombocytopenia (Table). Across all subgroups, at least three-quarters of patients reported symptoms were “improved” at week 24. Conclusions: 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 regardless of cytopenias. Clinical trial information: NCT01773187 , NCT02055781 . [Table: see text]
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.003 | 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".