Efficacy and Safety of Dasatinib in Patients with Chronic Myeloid Leukemia in Blast Phase Whose Disease Is Resistant or Intolerant to Imatinib: 2-Year Follow-Up Data from the START Program.
Notice bibliographique
Résumé
Abstract The prognosis for patients with myeloid-blast (MB) or lymphoid-blast (LB) chronic myeloid leukemia (CML) is poor, with an estimated survival from onset of blast crisis of approximately 3 months. Dasatinib (SPRYCEL®) is a novel inhibitor of BCR-ABL and SRC-family kinases, that has proven to be effective (in terms of complete hematologic and cytogenetic response) for patients with MB- or LB-CML whose disease is either resistant or intolerant to imatinib. Patients were enrolled to the corresponding START studies between January and June 2005, and dasatinib 70 mg BID was administered to 109 patients with MB-CML and 48 patients with LB-CML. All patients had previously failed treatment with imatinib - 90% of whom were resistant to imatinib. Here we present an update with a minimum follow-up of 12 mo. Of the 157 patients, 56% were male and median age was 54 years (range 17–81). Median time from CML diagnosis was 44 mo (range 2–216). Prior therapy included imatinib >600 mg/d in 50% of patients, treatment with imatinib for >3 years in 36%, and stem-cell transplantation in 19%. At baseline, 57% had WBC <20,000/mm3, 69% had platelets <100,000/mm3, and 18% had extramedullary disease outside of the spleen. Major hematologic responses (MaHRs) were induced in 34% of patients with MB-CML (imatinib-resistant 35%, -intolerant 20%) and 35% of LB-CML patients (imatinib-resistant 36%, -intolerant 33%). Major cytogenetic responses (MCyRs) were attained in 33% of patients with MB-CML (imatinib-resistant 34%, -intolerant 20%) and 52% of LB-CML patients (imatinib-resistant 50%, -intolerant 67%), while complete cytogenetic responses (CCyRs) were achieved in 26% (imatinib-resistant 26%, -intolerant 20%) and 46% of patients (imatinib-resistant 43%, -intolerant 67%), respectively. Median progression-free survival was 6.7 mo (MB-CML) and 3.0 mo (LB-CML) while median overall survival was 11.8 mo and 5.3 mo, respectively. Dasatinib was generally well tolerated in this poor prognosis population. Fluid retention events were observed more frequently in the MB-CML cohort, with all grade pleural effusion occurring in 36% and 13% of MB and LB patients, respectively (grade 3–4 - 15% and 6%). Other non-hematologic side effects were primarily grade 1–2. Cytopenias were noted for the majority of patients, and were manageable; grade 3–4 febrile neutropenia was recorded in 8% of patients. Dasatinib doses were reduced in 32% of patients and interrupted in 59%, most typically as a result of non-hematologic toxicities. Doses were escalated in 44% of patients. The median duration of therapy was 3.4 mo (0.03–18) for all patients and 14 mo (6–18) for patients still receiving treatment. Long-term data confirm that dasatinib is highly active, producing rapid and clinically meaningful responses in this poor prognosis patient population. Updated analyses corresponding to a minimum follow-up of 2 years on all patients will be presented.
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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 | 0,001 |
| 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 ».