Key Takeaways

• At the National Comprehensive Cancer Network (NCCN) 2026 Annual Congress: Hematologic Malignancies, Vivian G. Oehler, MD, presented criteria for tyrosine kinase inhibitor (TKI) dose de-escalation and discontinuation among patients with chronic myeloid leukemia (CML).
• Previous studies suggested that patients with low clinical risk scores can initiate TKI treatment at reduced doses and achieve comparable outcomes than those receiving full doses.
• Patients who achieved deep molecular response (DMR) are eligible for therapy de-escalation or discontinuation and maintain treatment-free remission (TFR).

At the NCCN 2026 Annual Congress: Hematologic Malignancies, Vivian G. Oehler, MD, associate professor in the Translational Science and Therapeutics Division at Fred Hutchinson Cancer Center, discussed strategies of TKI dose de-escalation for patients with CML.

Treatment goals for CML include improving survival outcomes and quality of life, minimizing adverse events, limiting costs, and achieving TFR. De-escalating and discontinuing TKI therapy may accomplish most of these goals, but only for select patients.

By reviewing case studies and data from previous clinical trials, Dr Oehler identified characteristics that make a patient eligible for dose reduction and explored different methods of de-escalation.

Therapy De-Escalation

According to Dr Oeherl, clinical risk scores can help physicians choose frontline regimens for patients with CML. Since higher risk scores are associated with poor survival outcomes, these patients should receive full doses of second-generation TKIs such as dasatinib, nilotinib, and bosutinib. Patients with lower risk scores can be treated with low doses of any first- or second-generation TKI.

Recent research suggests low-dose TKI therapy and escalating to achieve major molecular response (MMR) rather than the other way around. In studies evaluating the impact of upfront low dosing for dasatinib, bosutinib, and nilotinib, lower doses of these drugs demonstrated similar efficacy.

Other studies, including the DESTINY and phase 3 BFORE trials, found that patients can maintain MMR and TFR after reducing TKI doses. By monitoring BCR::ABL1 transcripts, researchers in the DESTINY trial developed a risk prediction model to identify patients likely to have molecular reoccurrence.

Dr Oehler noted that adverse events can occur in low-dose regimens, and therapy switching may help manage toxicity.

TKI Discontinuation

Stopping TKI therapy entirely and maintaining TFR has had mixed success in previous trials, with TFR rates ranging from 40% to 65%.

NCCN guidelines advise therapy discontinuation after 3 years of treatment and 2 years of MR4. Optimal discontinuation criteria, according to the European LeukemiaNet (ELN), are at least 5 years of treatment and 3 years of MR4.

Treatment Strategies

For frontline treatments, Dr Oehler suggested full TKI dosing for younger patients and those with high clinical risk scores. Patients with lower risk scores and multiple comorbidities can begin TKI treatment at reduced doses.

In later lines of therapy, patients at low risk of disease transformation can begin treatment de-escalation. Patients with less than 1% of BCR::ABL1 or who achieved MMR are also eligible for therapy de-escalation or discontinuation.

Reference

Oehler VG. Chronic myeloid leukemia: de-escalation of TKI therapy. NCCN 2026 Annual Congress: Hematologic Malignancies. September 18-19, 2026. New York, NY. Accessed September 18, 2026. https://web.cvent.com/hub/events/adf6c070-106a-43d2-a77f-5e2ff9397670/sessions/4006ede8-771f-43ab-a87e-c3a429532086?autoPlay=false