PS1065 OPEN‐LABEL STUDY OF GILTERITINIB, GILTERITINIB PLUS AZACITIDINE, OR AZACITIDINE ALONE IN NEWLY DIAGNOSED FLT3‐MUTATED AML PATIENTS INELIGIBLE FOR INTENSIVE CHEMOTHERAPY: RESULTS FROM THE SAFETY COHORT
Notice bibliographique
Résumé
Background: The FLT3 inhibitor, gilteritinib, showed antileukemic activity and favorable tolerability in patients (pts) with FLT3 ‐mutated ( FLT3 mut+ ) relapsed/refractory AML. Gilteritinib plus azacitidine (AZA) induced apoptosis and inhibited MV4–11 cell and tumor growth. A clinical trial investigating gilteritinib plus AZA vs either agent alone in pts with newly diagnosed (ND) FLT3 mut+ AML ineligible for intensive induction chemotherapy was initiated; we present data from the Safety Cohort, which evaluated combination therapy. Aims: A clinical trial investigating gilteritinib plus AZA vs either agent alone in pts with newly diagnosed (ND) FLT3 mut+ AML ineligible for intensive induction chemotherapy was initiated; we present data from the Safety Cohort, which evaluated combination therapy. Methods: Adults with ND FLT3 mut+ AML are being enrolled in this clinical trial (NCT02752035). To determine the appropriate gilteritinib dose for combination therapy prior to the randomized portion of the study, a Safety Cohort was initiated, in which pts received 80 or 120 mg/day gilteritinib (Days 1–28) plus subcutaneous/intravenous AZA (75 mg/m 2 /day; Days 1–7) and were observed for dose‐limiting toxicities (DLTs) through Cycle 1. Treatment continued until lack of clinical benefit or unacceptable toxicity. Safety/tolerability and antileukemic response were assessed. Results: Fifteen pts (median age, 76 years [range: 65–86]) were enrolled into the Safety Cohort (n = 9, 80 mg gilteritinib; n = 6, 120 mg gilteritinib); 14 were FLT3 mut+ (ITD alone, n = 10; TKD alone, n = 3; ITD and TKD, n = 1). As of 25 June 2018, 56% (n = 8/15; Figure) of pts had been treated for >6 mo, 9 discontinued, and 6 remained on treatment. A DLT (tumor lysis syndrome) occurred in a pt who received 80 mg gilteritinib plus AZA; no DLTs occurred in the 120 mg gilteritinib plus AZA cohort. All 15 pts had ≥1 AE; 12 (80%) experienced treatment‐related AEs. Common AEs were anemia (n = 7), febrile neutropenia and nausea (n = 6 each), increased ALT/AST, constipation, diarrhea, neutropenia, thrombocytopenia, and pyrexia (n = 5 each), and decreased appetite, fatigue, increased blood creatinine, and hypocalcemia (n = 4 each). Common grade ≥3 AEs were febrile neutropenia (n = 6), anemia and neutropenia (n = 5 each), and thrombocytopenia (n = 4). Serious AEs in >2 pts were febrile neutropenia (n = 5), and anemia and pyrexia (n = 3 each). Eight pts had fatal AEs; none were treatment‐related and 3 occurred early in treatment: septic shock (Day 2), respiratory failure (Day 6), and cerebral hemorrhage in the setting of acute kidney injury and uremia (Day 17). Of 13 pts with post‐baseline laboratory data, none had clinically significant AST/ALT or total bilirubin values or maximum post‐baseline QTcF interval >500 msec. The composite complete remission rate was 67% (n = 10/15); complete remission and complete remission with incomplete hematologic recovery was achieved in 4 and 6 pts, respectively (Figure); 2 pts (13%) achieved a partial response, giving an overall response rate of 80%. One DLT from the 11 DLT‐evaluable pts (ie, pts who experienced a DLT, or in the absence of DLT, received ≥23 of 28 gilteritinib doses and ≥5 of 7 AZA doses during DLT observation) informed the decision to proceed to randomization at 120 mg/day gilteritinib for combination treatment. Summary/Conclusion: In ND FLT3 mut+ AML pts unfit to receive standard induction chemotherapy, gilteritinib and AZA were well tolerated, and induced antileukemic responses. Based on these results, enrollment into the randomized portion of the study has begun and pts in the combination arm will receive 120 mg gilteritinib. image
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 | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 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 | 0,001 | 0,001 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 ».