PS1460 LONG-TERM FOLLOW UP OF JAK INHIBITOR (JAKI) TREATED PATIENTS WITH MYELOFIBROSIS: IMPACT OF MOLECULAR ENHANCED INTEGRATED SCORING SYSTEMS AND TYPE OF JAKI THERAPY FAILURE ON SURVIVAL
Notice bibliographique
Résumé
Background: Janus kinase (JAK) 1/2 inhibitors (JAKi) are the mainstay of treatment for symptomatic myelofibrosis (MF). Research to date has primarily focused on predicting which patients are unlikely to have durable responses. Despite approximately half of patients discontinuing therapy by three years, data on the type of JAKi failure and associated long term outcomes is limited. Furthermore, standardized criteria for determining JAKi failure is difficult to apply in clinical practice and greater understanding of this area is needed to assist treatment decisions. Aims: To describe the type of JAKi failure and to associate failure type with time to treatment failure (TTF) and overall survival (OS). We also explored whether baseline clinical and disease characteristics including molecular enhanced integrated scoring systems, predicted type of treatment failure Methods: Patients with chronic phase MF and treated with JAKi therapy were included in the study. Type of failure was defined as: transformation to accelerated or blast phase; hematological toxicity including thrombocytopenia (sustained platelet count <50) or new onset transfusion dependence (≥6 units in 12 weeks); or spleen progression/loss of spleen response (as per revised IWG-MRT criteria). Molecular analysis was performed by targeted sequencing using a 54 myeloid gene panel. TTF and OS endpoints were estimated by using Kaplan-meier method. Univariate and multivariable analysis was performed using Cox proportional hazards model. Results: One hundred patients (median age: 68yrs) with a diagnosis of chronic phase MF (2 pre-fibrotic MF; 48 overt MF; 27 PPV-MF; 23 PET-MF) and treated with JAKi therapy (77 ruxolitinib; 23 momelotinib) were eligible. With a median follow-up of 3.5yrs, 69 (69%) patients failed JAKi therapy. Reasons included: transformation to accelerated or blast phase (n = 12), hematological toxicity (n = 17) due to thrombocytopenia (n = 9) or transfusion dependence (n = 8) and spleen progression/loss of spleen response (n = 40). Thirty one patients did not fail Jaki therapy: nine patients continue on JAKi therapy (median duration: 4.6yrs, range: 4.0–8.1yrs) with sustained clinical improvement; five patients proceeded to allogeneic stem cell transplant after clinical response; two patients were lost to follow-up; 15 patients discontinued JAKi therapy due to non-hematological toxicity while responding (secondary malignancy = 4, sepsis = 3, acute kidney injury = 3, neurological = 2, other = 3). On univariate analysis, type of treatment failure was associated with OS (p = 0.05) and became more significant on multivariable analysis (p = 0.01). Patents with failure due to spleen progression/loss of response had the longest median OS following treatment failure at 1.2yrs, as compared to hematological toxicity (median OS: 0.7yrs; HR: 1.71) and transformation to accelerated/blast phase (median OS: 0.3yrs; HR: 2.22) (p < 0.001)(Figure 1). Baseline clinical variables, complete blood count parameters and prognostic scores including MIPSS70, MIPSS70-plus, were not associated with type of treatment failure. There was no correlation between reason for JAKi failure and TTF. Other variables associated with shorter TTF and OS included: pre-treatment transfusion dependence (p = 0.01; p = 0.04), higher MIPSS70 (p = 0.003; p = 0.01) and higher MIPSS70-plus (p = 0.002; p = 0.01).Summary/Conclusion: This study provides a greater understanding of the outcomes for patients failing JAKi therapy. Information obtained may assist the clinician in determining future management of these patients and provide enhanced guidelines for JAKi failure.
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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) | 0,001 | 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 ».