TKI Dose De-Escalation Preserves Treatment-Free Remission in CML, Study Finds

Key Clinical Summary

• TKI dose de-escalation did not compromise treatment-free remission (TFR) among adults with chronic myeloid leukemia (CML) treated at a US academic center.
• Patients receiving dose-reduced therapy were more likely to achieve undetectable BCR::ABL1 transcripts than those maintained on standard-dose treatment before attempting TFR.
• Dose de-escalation also significantly reduced adverse events, supporting its role as a strategy to maintain clinical outcomes while improving treatment tolerability.

Treatment with tyrosine kinase inhibitors (TKIs) has transformed chronic myeloid leukemia (CML) into a chronic, manageable disease, but long-term therapy can lead to cumulative toxicities. In a retrospective analysis of patients treated at Oregon Health & Science University (OHSU), investigators found that TKI dose de-escalation preserved TFR outcomes while reducing adverse events and supporting deep molecular responses.

Study Evaluates Clinical Outcomes After TKI Dose Reduction

Investigators retrospectively analyzed 407 adults with CML treated with TKIs at OHSU. The primary outcomes included TFR and achievement of undetectable BCR::ABL1 transcripts. Odds ratios (ORs) and Cox proportional hazards regression hazard ratios (HRs) were used to evaluate predictors of clinical outcomes.

The median age at diagnosis was 48 years (range, 18-91 years), with a median follow-up of 11.3 years. Initial TKI therapy consisted of imatinib in 252 patients (62%), dasatinib in 95 (23%), nilotinib in 42 (10%), bosutinib in 10 (2%), and third-generation or later TKIs in the remaining 2%. Nearly half of patients (46%) remained on their initial TKI, while 54% received at least 2 TKIs during treatment. Only 13 patients (3.2%) underwent bone marrow transplantation.

Among the 133 patients who attempted TFR, 52 (39%) remained on standard-dose therapy, whereas 81 (61%) underwent TKI dose de-escalation before their first TFR attempt. Investigators found no significant differences in TFR between the groups (HR, 1.07; 95% CI, 0.59-1.96; P = .818). TFR rates at 1 year were 77% for the standard-dose group and 74% for the dose de-escalation group. At 2 years, both groups maintained a 69% TFR rate.

At the last follow-up, 89 patients remained in TFR, and 62% of those patients had previously undergone dose de-escalation.

Among the 274 patients who had not attempted TFR, 162 continued treatment with their initial TKI. Dose reduction occurred in 56 patients (34%), and 9 (16%) achieved undetectable disease compared with 5 of 106 patients (5%) receiving standard doses (OR, 3.83; 95% CI, 1.08-15.40; P = .020). Investigators also reported that dose de-escalation significantly reduced adverse events.

Dose Reduction May Improve Tolerability Without Sacrificing Disease Control

Long-term TKI therapy is associated with cumulative toxicities that may affect quality of life and treatment adherence. The findings from this analysis suggest that carefully selected patients may benefit from dose de-escalation without compromising key clinical outcomes, including the ability to achieve and maintain TFR.

The study also demonstrated an association between dose reduction and a greater likelihood of achieving undetectable BCR::ABL1 transcripts among patients who had not yet attempted TFR. Combined with the observed reduction in adverse events, these results support dose optimization as a potential strategy for balancing treatment efficacy and long-term tolerability in patients with CML.

Because the study was retrospective, the findings should be interpreted within the context of the study design. However, the large cohort and extended follow-up provide additional insight into the role of TKI dose de-escalation in routine clinical practice.

Investigators Support Rational TKI Dose De-Escalation

The investigators concluded that patients who underwent TKI dose de-escalation did not experience significant differences in the duration or rate of TFR compared with those receiving standard-dose therapy. They further reported that patients receiving dose-reduced treatment were more likely to achieve undetectable disease and experienced significantly fewer adverse events. Based on these findings, the authors stated that rational dose de-escalation may preserve important clinical outcomes while reducing treatment-related toxicity.

These findings suggest that TKI dose de-escalation may represent a practical approach for selected patients with CML, offering an opportunity to reduce treatment-related adverse events while maintaining durable disease control and supporting long-term treatment goals, including TFR.

Reference

Pusung M, Eide C, Kaempf, et al. Outcomes and responsiveness of standard tyrosine kinase inhibitor dose versus dose de-escalation in chronic myeloid leukemia: a single-center retrospective study. J Clin Oncol. 2026;44(16):6598. doi:10.1200/JCO.2026.44.16_suppl.6598