P561: REVUMENIB IN PATIENTS WITH ACUTE LEUKEMIAS: COMPASSIONATE USE PROGRAM EXPERIENCE
Notice bibliographique
Résumé
Background: Revumenib (REV; SNDX-5613), a menin inhibitor, is under investigation in patients (pts) with relapsed/refractory (R/R) acute leukemia harboring a KMT2A rearrangement (KMT2Ar) or NPM1 mutation. A phase 1/2 study, AUGMENT-101 (NCT04065399), is ongoing; preliminary data were presented (Issa. Blood. 2022). Phase 2 initiated with a recommended dose of 163 mg q12h for pts receiving a strong cytochrome P450 3A4 inhibitor. A compassionate use program was available for pts ineligible or unable to enroll in AUGMENT-101 if slots were unavailable or sites were not yet open. Aims: To report REV compassionate use outcomes. Methods: Pts from the US, UK, France, Israel, Lithuania, Canada, and The Netherlands with R/R acute leukemia were treated with REV. Demographics, outcomes, and safety data were collected from single-pt protocols, physician communications, and source documents. Results: From Oct 2019 to Dec 2022, 36 pts (20 female) with R/R acute leukemia received REV. Ages ranged from 1.2 to 71 years (20 pediatric pts [<18 y]). Leukemia subtypes were acute myeloid leukemia (AML; n=30), acute lymphoblastic leukemia (n=4), and mixed phenotype acute leukemia (n=2). Most pts had KMT2Ar (n=34) and were heavily pretreated (≥3 prior regimens [n=26]; range, 1-6); 23/36 had prior hematopoietic stem cell transplant (HSCT). Thirty pts had active disease evaluable for response. Nine pts received prior REV on AUGMENT-101, achieved a response, and proceeded to HSCT but were ineligible to restart REV on trial. These pts received REV compassionate use as maintenance (n=6) or following relapse post-HSCT (n=3). The other reasons for trial ineligibility included age <18 y before AUGMENT-101 amendment reduced the minimum age to 30 d, concurrent malignancy, myeloid sarcoma, ongoing graft vs host disease, and prior menin inhibitor exposure. Of the 30 pts with active disease evaluable for response (19 pediatric), 4/19 pediatric pts reported a response, with 2 achieving minimal residual disease (MRD)–negative complete response (CR), 1 CR, and 1 CR-incomplete hematologic recovery (CRi); 3 of the 4 pts proceeded to transplant. One of 11 adults converted from MRD-positive to MRD-negative disease. Another adult had progressive disease (PD) as best response on 2 other prior menin inhibitors and best response of PD with REV. Of the 30 pts, 3 adults previously responded to REV on AUGMENT-101, proceeded to HSCT, and experienced relapse post-transplant; 2/3 were re-treated for 80 and 115 d before progressing and 1/3 remained on treatment after 2 28-d cycles. An additional 6 pts (5 adults) received REV as maintenance therapy after achieving CR-partial hematologic recovery, CR-incomplete platelet recovery, or morphological leukemia-free state with REV on AUGMENT-101 and proceeding to HSCT or CD34+ boost. At data cutoff, 3/6 pts remained in remission and on treatment as of d 338, d 223, and d 158; 1/6 discontinued on d 30 and was reported well on d 285; and 2/6 progressed on d 160 and d 34. Given the nature of the compassionate use program, adverse events (AEs) were not consistently reported among all 36 pts. Reported AEs were consistent with common AEs in trials of pts with R/R acute leukemia, including thrombocytopenia (n=7), and with those of ongoing REV trials including differentiation syndrome and QTc prolongation (n=3 each). Summary/Conclusion In this compassionate use program, which included heavily pretreated pts, disease responses were observed. Several pts who started REV as maintenance post-HSCT experienced prolonged remissions. No new safety signals were reported. Keywords: Acute lymphoblastic leukemia, Acute leukemia, Acute myeloid leukemia, Relapsed acute lymphoblastic leukemia
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 | 0,001 |
| 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 ».