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

Abstract

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.