Real-world treatment patterns, outcomes, and unmet needs in patients with ph+ ALL receiving tyrosine kinase inhibitors in the United States: Emerging trends and the role of asciminib-based combinations
Notice bibliographique
Résumé
Abstract Background: Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is the predominant genetic ALL subtype in adults. Tyrosine kinase inhibitor (TKI)-based therapies constitute the mainstay of treatment. Recently, asciminib-based regimens have been incorporated into the NCCN Guidelines (Version 1.2025) as a recommended treatment option for relapsed/refractory Ph+ ALL, based on the study by Luskin et al. (Blood 2025;145[6]:577–589). This study evaluated treatment patterns, with a focus on emerging trends and asciminib use, and real-world outcomes in patients (pts) with Ph+ ALL in US clinical practice. Methods: This retrospective cohort study included adult Ph+ ALL pts treated with TKIs. Data came from HealthVerity, a large US nationwide insurance claims database (2016-2024). The index date was defined as the first observed TKI claim (index TKI). Using index TKI, treatment patterns were described overall and by index year period to assess changes in the treatment landscape as new treatments emerged (i.e., 2016-2019, 2020-2022, 2023-2024). Subgroup analysis was conducted among pts with ≥1 claim for asciminib. Real-world outcomes, including relapse diagnosis and clinical events associated with TKI-related conditions, were descriptively reported. Results: Overall, 3,002 pts were included (median age 48 years, 48% female, 56% commercially insured, 35% Medicaid, 10% Medicare Advantage). Among these, 1,564 (52%) pts had their first TKI claim (index) observed in 2016-2019, 959 (32%) in 2020-2022, and 479 (16%) in 2023-2024. Mean (median) follow-up period from index was 30 (22) months. Most pts (64%) were observed with a single TKI agent during the follow-up period, with mean (median) treatment duration of index TKI of 22 (13) months. The main index TKIs were dasatinib (59%), ponatinib (16%), and imatinib (18%). A second TKI was observed in 26% of pts, and 9% had a third or more TKIs. Anytime during the follow-up period, 67% received dasatinib, 35% ponatinib, 24% imatinib, 13% nilotinib, 6% bosutinib, and 66 (2%) asciminib-based therapy. Based on the index TKI, treatment patterns evolved over time, with important shifts between 2016 and 2024. The use of dasatinib declined from 60% among pts with index in 2016-2019 and 61% in 2020-2022, to 51% in 2023-2024. The use of imatinib also decreased from 24% among pts with index in 2016-2019, to 13% in 2020-2022 and 8% in 2023-2024. Meanwhile, the uptake of ponatinib increased substantially, with 7% of pts with index in 2016-2019, to 19% in 2020-2022 and 37% in 2023-2024. Similarly, the use of TKI-based combinations with blinatumomab increased from 7% among pts with index in 2016-2019, to 20% in 2020-2022 and 26% in 2023-2024. Ten pts had CAR-T cell therapy. The HCT use varied, with an increase from 51% of pts with index in 2016-2019 to 62% in 2020-2022, then a decrease to 52% in 2023-2024. Overall (N=3,002), 34% of pts had a relapse diagnosis post-index, with 17% occurring during index TKI use. Furthermore, while on index TKI, 32.5% of pts had a clinical event with a diagnosis for pleural effusion, 17.0% for an arterial occlusive event (myocardial infarction, ischemic cardiovascular event, angina), and 70% for a gastrointestinal event (nausea, vomiting, constipation, diarrhea). For the asciminib subgroup (N=66), the mean (median) duration of asciminib was 7 (4.5) months. Before asciminib, 94% received ≥1 TKI, most commonly ponatinib (61%) or dasatinib (14.5%) immediately prior. Most pts underwent HCT (74%), with 64% (N=42) prior to asciminib initiation and 36% (N=24) afterward. Relapse diagnosis was observed in 56% of pts before asciminib initiation. Asciminib was given as combination therapy (82%) with corticosteroids (76%), chemotherapy (64%), inotuzumab ozogamicin (16%), and blinatumomab (15%). Conclusion: This real-world study described evolving patterns in the management of pts with Ph+ ALL. In recent years, increased use of ponatinib and immunotherapy has been observed alongside a decline in use of dasatinib and imatinib. Despite therapeutic advances, many pts experienced clinical events associated with TKI-related conditions, and one-third had disease relapse. Asciminib has mainly been used as part of combination therapy, most commonly in later lines of treatment in the post-relapse setting of Ph+ ALL. These findings suggest that treatment options with greater potency, broader spectrum of activity, and lower toxicity may improve disease management.
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 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,002 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 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 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 ».