Analysis of hematologic improvement (HI) by time to response in Relapsed/Refractory Acute Myeloid Leukemia (AML) patients treated with olutasidenib
Notice bibliographique
Résumé
Abstract Background Olutasidenib is a potent, selective, oral inhibitor of mutated IDH1 (mIDH1) approved for the treatment of relapsed or refractory (R/R) mIDH1 AML. The phase 2 pivotal cohort (NCT02719574) demonstrated efficacy and tolerability of olutasidenib, with a complete remission (CR)/CR with partial hematologic recovery (CRh) rate of 35% and a median duration of CR/CRh of 25.3 months. This analysis evaluated baseline characteristics and changes in platelet count, hemoglobin levels, and blast percentages by time to response (TTR) among patients in the pivotal cohort. Methods Adult patients with R/R mIDH1 AML were treated with olutasidenib 150 mg BID. Patients were stratified by best overall response and TTR: <2 months, 2 to 4 months, and >4 months. Hematologic characteristics, including platelet counts, hemoglobin levels, and blast burden were evaluated over the course of olutasidenib treatment. Results Among 147 efficacy-evaluable patients, the median age was 71.0 years (range 32.0, 87.0) and 50% were female. Mean baseline hemoglobin levels, platelet counts, and blast percentages were 9.7 g/dL, 87.2×109/L, and 45.2%, respectively. In the overall cohort (N=147), increases in hemoglobin were seen early in the course of treatment and levels continued to increase over 12 cycles; a mean of 11.0 g/dL was seen at cycle 6. Similarly, platelet counts increased and blast percentages decreased over the course of treatment, with a mean platelet count of 136.3×109/L and blast percentage of 14.2% at cycle 6. A total of 71 patients (48%) achieved overall response criteria; 47 patients (32%) achieved CR and 51 (35%) achieved CR/CRh. Among CR/CRh responders, 28 (55%) achieved a response in <2 months, 17 (33%) from 2 to 4 months, and 6 (11.7%) at >4 months. Patients with TTR >4 months had lower baseline platelet counts and hemoglobin levels and higher blast percentages compared with earlier responders. Mean hemoglobin level of 12 g/dL was achieved by cycle 4, 6, and 8 in <2, 2-4, and >4 month TTR groups, respectively. Mean blast count below 5% was achieved by cycle 2 in the <2 month TTR group, by cycle 4 in the 2-4 month TTR group, and by cycle 6 in the >4 month TTR group. Additionally, in 37 patients (25%) who had a best response of stable disease (SD), several showed improvement in platelets and hemoglobin levels by end of treatment, including 7 of 21 (33%) who were previously transfusion-dependent for platelets became independent and 7 of 23 (30%) who were previously transfusion-dependent for red blood cells became independent. Conclusions Later responders tended to have lower baseline platelet counts and higher bone marrow blast percentages, suggesting lower hematopoietic reserve and greater disease burden. Some patients with best overall response of SD experienced modest improvements in hematologic parameters, including platelets, hemoglobin, and transfusion independence. These findings suggest that continuing olutasidenib treatment beyond 2 cycles may offer hematologic benefits, even in the absence of an early clinical response.
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 machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| 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) | 0,001 | 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 source (Gemma direct ou Codex distillé), 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 ».