Prevalence of Dosage Modifications and Impact on Response Milestone Among Patients With CML Treated With Imatinib Using RWD

A group of experts will present an encore abstract titled "Prevalence of Dosage Modifications and Impact on Response Milestone Among Patients With CML Treated With Imatinib Using Real-World Data" at the 2025 Oncology Pharmacists Connect (OPC) meeting in Austin, Texas, from June 19 to 20. The abstract was originally shared at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

Image Credit: © catalin - stock.adobe.com

The abstract authors explore how dosage modifications—such as reductions, interruptions, and discontinuations—affect clinical response milestones in patients with chronic myeloid leukemia (CML) treated with imatinib (Gleevec; Novartis Pharmaceuticals Corporation). Drawing on electronic health records from a large integrated health system, the study found that nearly half of patients experienced at least 1 dosage modification within the first year of therapy, with such changes linked to a lower likelihood of achieving 6-month molecular response milestones. Ultimately, the findings highlight the need for closer monitoring and further research to understand the long-term clinical impact of dose adjustments in real-world CML treatment settings.

Abstract

Background

Targeted therapy with BCR-ABL1 tyrosine kinase inhibitors (TKIs), such as imatinib, is the cornerstone of chronic myeloid leukemia (CML) treatment. However, dosage modifications affect clinical outcomes. This study aims to assess the prevalence of dosage modifications, including interruptions and reductions, and their impact on the efficacy of BCR-ABL1 TKIs in patients with CML.

Materials and Methods

This retrospective observational study utilized the Carolina Data Warehouse for Health electronic health record (EHR) database. Eligible patients include adults (≥ 18 years) diagnosed with CML receiving imatinib as first-line therapy for more than 1 month between 2008 and 2023. Patients with incomplete dosing data were excluded. Descriptive statistics include the types and prevalence of dosage modifications, including dose reduction, dosage interruption, and drug discontinuation. Efficacy analyses were evaluated using BCR-ABL transcripts and early response milestones at 3, 6, and 12 months. Statistical analyses were performed using the Fisher exact test, with a 2-sided α level of 0.05.

Results

A total of 118 patients were included, with a median age of 61 years, mostly women (55%), and representative of diverse racial and ethnic backgrounds (59% White, 26% Black, 2% Asian, 1% American Indian, 7% Hispanic, and 5% other/unknown). Of these patients, 59 (50%) experienced a total of 112 all-cause dosage modification events during the first year of use: dose reductions (30/112, 26%), dosage interruptions (51/112, 46%), dose discontinuations (28/112, 25%), and others (3/112, 3%). Fifty-two percent (58/112) of dose modification events occurred in the first 6 months. Additionally, 39 patients (66%) experienced dosage modifications due to toxicities, and 4 patients (3%) initiated treatment at a reduced dose of imatinib.

Among the patients with evaluable response data, 56 of 84 (67%) patients achieved an early molecular response (BCR-ABL < 10%) at month 3, 48 of 72 (67%) patients achieved less than 1% at month 6, and 41 of 67 (61%) patients achieved less than 0.1% at month 12. Dosage modifications were associated with a reduced likelihood of achieving 6-month milestones (P < .05) but were not significantly associated with outcomes at 3 (P = .33) or 12 months (P = .52).

Conclusions

We demonstrated the feasibility of leveraging a complex EHR data source from an integrated health system to study the impact of dose modifications on clinical outcomes for self-administered chemotherapy. Nearly half of the patients with CML on imatinib experienced dosage modifications in this study. Although these modifications were associated with a lower likelihood of achieving 6-month molecular response milestones, this finding has various limitations due to the sample size, retrospective nature, and lack of adjustment for multiple comparisons in this study. Our cohort of patients experienced more treatment discontinuations due to toxicities when compared with clinical trials. Additional analyses are needed to further evaluate the long-term impact and causal effect of dosage modifications due to toxicities on clinical outcomes.

About the 2025 OPC Meeting

At this year’s OPC meeting, attendees will have the opportunity to showcase clinical research and practice management insights or explore the latest advancements in oncology pharmacy during the poster session and networking reception. These events foster innovation, collaboration, and professional growth within the oncology pharmacy community. Participants can present their work, exchange ideas, and connect with leaders in the field during these networking opportunities.

Prior to the start of OPC on June 19, participants are invited to attend the Hematology/Oncology Pharmacy Association (HOPA) BCOP Program in person on June 18. HOPA has selected 4.0 CE hours from BCOP Updates 2024 and the Annual Conference 2025, featuring topics such as acute leukemia, cellular therapy for solid tumors, and the pharmacist’s role in serious illness conversations. Additional information is available here.