P1037: CONSISTENCY OF PACRITINIB FOR SPLEEN AND SYMPTOM REDUCTION IN PATIENTS WITH MYELOFIBROSIS REGARDLESS OF CYTOPENIAS
Notice bibliographique
Résumé
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
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».