NCCN Flash Update: Updated CML Guidelines Emphasize Distress Screening, Drug Interactions, and Cost

The National Comprehensive Cancer Network (NCCN) has published version 1.2026 of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for chronic myeloid leukemia (CML), accompanied by updates to the NCCN Drugs & Biologics Compendium. These revisions reflect a broader focus on individualized treatment selection, clinical pharmacology, safety monitoring, and cost considerations. Oncology pharmacists play an essential role in implementing these updates, particularly in the selection and management of tyrosine kinase inhibitor (TKI) therapy and drug interactions, as well as in counseling patients on evolving standards of care.

Holistic Patient Assessment and Molecular Workup

The updated guidelines include a new recommendation to assess for patient distress as part of the initial CML workup, accompanied by a footnote referring providers to the NCCN Distress Management Thermometer and Problem List. This screening tool includes consideration of social determinants of health and reflects the shift toward comprehensive, patient-centered care. Additionally, in chronic-phase CML, clinicians are now advised to consider myeloid mutational analysis as a category 2B recommendation, especially when evaluating atypical presentations or treatment resistance.

Expanded Treatment Considerations Beyond Risk Score

Newly added treatment considerations emphasize the importance of the BCR::ABL1 transcript type, TKI dosing schedule, treatment goals, and medication cost—each now listed as separate bullets in the updated treatment algorithms. These factors should be considered independently of risk score models and highlight the trend toward more nuanced and individualized treatment decision-making.

Pharmacists should be particularly aware that asciminib (Scemblix;Novartis) is now contraindicated in patients with BCR::ABL1 fusion transcripts lacking ABL1 exon 2, such as b2a3 or b3a3 isoforms, due to a lack of clinical activity in these subgroups. This recommendation is supported by recent findings published in Leukemia and appears across multiple sections in the NCCN Guidelines, including CML-2A, CML-4A, and CML-5.

Pharmacoeconomic and Formulation Guidance

Several footnotes now emphasize the significant cost difference between brand name and generic TKIs. Pharmacists are encouraged to consider not only patient affordability but also system-level cost burdens. Notably, the guidelines affirm that FDA-approved generics are appropriate substitutes for brand-name agents, assuming regulatory pharmacokinetic equivalence. However, clinicians should remain alert to potential pharmacokinetic variability during transitions, particularly with agents such as nilotinib (Danziten; Azurity) and bosutinib (Bosulif; Pfizer), which have narrow therapeutic windows.

The guidelines also note that TKIs are available in different dosage forms, strengths, and formulations, which are not interchangeable. Pharmacists should refer to the specific package inserts to ensure correct administration.

Pregnancy Management and Interferon Use

The 2026 update reinforces that TKI therapy should generally be avoided during pregnancy due to teratogenic risks, particularly in the first trimester. When treatment is necessary, interferon alfa-2a is preferred. In the United States, peginterferon alfa-2a (Pegasys; pharma& GmbH) and ropeginterferon alfa-2b (BESREMi; PharmaEssentia Corporation) are available for clinical use, but the latter has very limited data supporting its use in pregnant patients with CML. Updated references provide additional real-world evidence on interferon use in pregnancy and essential thrombocythemia.

Updated Drug Interaction Tables and New Cautions

The CML drug interaction sections (CML-D) have been substantially expanded and clarified, particularly around acid-suppressing agents and CYP3A4-interacting foods. New guidance advises avoiding coadministration of TKIs with H2 receptor antagonists, proton pump inhibitors (PPIs), and antacids when possible. If such use is unavoidable, specific timing recommendations are provided—for instance, administering antacids at least 2 hours before or after TKIs such as bosutinib, dasatinib (Sprycel; Bristol Myers Squibb), or nilotinib.

Importantly, the guidelines now acknowledge the FDA approval of a pH-independent formulation of dasatinib that allows for concurrent use with PPIs and H2 receptor antagonists. Additionally, a new table lists fruits and juices (eg, grapefruit, star fruit, black mulberry, wild grape, and pomegranate) that should be avoided due to their potential to increase TKI exposure via CYP3A4 inhibition.

Atorvastatin has also been added to the list of cardiovascular medications with potential interactions, a common issue in older or comorbid patients with CML.

Mutation-Guided Therapy and TKI Selection

Further clarity has been added to the section on treatment recommendations based on BCR::ABL1 mutation and variant profiles. The term Contraindicated Mutations has been updated to Contraindicated Mutations/Variants, and guidance has been added noting that certain kinase domain mutations may confer differential sensitivity to TKIs based on IC50 values.

A key update for ponatinib (Iclusig; Takeda Pharmaceuticals) includes a recommendation to initiate therapy at lower doses and reduce dosage in responders, with close monitoring to mitigate cardiovascular toxicity. This individualized dosing approach aims to balance efficacy with safety and aligns with broader trends in precision oncology.

Monitoring for Disease Progression and Toxicities

The revised guidelines encourage clinicians to perform bone marrow evaluation to assess for progression to accelerated phase or blast phase following TKI therapy, especially in patients presenting with persistent cytopenias. In the blast phase section, both myeloid and lymphoid subtypes are now distinctly identified, and language has been clarified around the clinical concern for increasing lymphoblasts.

Guidance on adverse event monitoring has also been updated. Patients should be educated to report abdominal pain (a potential sign of pancreatitis), and hepatic function should be closely monitored through liver function tests, particularly for elevations in aspartate transaminase, alanine transaminase, or bilirubin.

Criteria for TKI Discontinuation

The age requirement (≥18 years) for TKI discontinuation has been removed, broadening eligibility. Updated references from the EURO-SKI study and recent publications in the Journal of Clinical Oncology and Leukemia outline the most significant predictors of successful discontinuation. These include sustained MR4.0 for at least 3 years, total TKI therapy duration of 6 years or more, and disease characteristics at diagnosis. Duration of TKI exposure remains the most consistent predictor of long-term molecular response post-discontinuation.

Implications for Pharmacy Practice

Overall, these updates underscore the central role of the oncology pharmacist in guiding individualized treatment selection, identifying and managing drug interactions, educating patients, and optimizing cost-effective care. Pharmacists are particularly vital in implementing molecularly informed prescribing, ensuring safe formulation use, and managing therapy during unique life stages such as pregnancy.

REFERENCE

NCCN. Clinical Practice Guidelines in Oncology.Chronic myeloid leukemia, version 1.2026. July 16, 2025. Accessed July 18, 2025. https://www.nccn.org/professionals/physician_gls/pdf/cml.pdf