TKI-Treated CML Survivors Face Long-Term Health and Functional Challenges

Key Clinical Summary

• Long-term survivors of chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs) had greater odds of poor general health, functional impairment, activity limitations, and pre-frailty or frailty than individuals without CML.
• Overall, 71.0% of TKI-treated patients had at least 1 adversely affected health domain, compared with 42.6% of non-CML controls.
• Health status was generally comparable between TKI-treated patients and CML survivors who underwent blood or marrow transplantation (BMT), although activity limitations were more likely with TKI treatment.

TKIs have substantially reduced CML-related mortality, but long-term survivors may experience persistent health limitations, according to findings from the BMT Survivor Study (BMTSS). After a median 12.5 years of follow-up, TKI-treated patients with CML reported worse health across several domains compared with individuals without CML.

Long-Term Health Status After TKI Treatment

Researchers evaluated 62 patients with CML treated with TKIs who had not undergone BMT and compared them with 303 individuals without CML and 220 patients with CML treated with BMT without TKI exposure. Median follow-up was 12.5 years for the TKI cohort and 19.4 years for the BMT cohort.

Participants self-reported general health, functional status, activity limitations, and pre-frailty or frailty. At least 1 domain was adversely affected in 71.0% of TKI-treated patients, compared with 42.6% of non-CML controls and 65.9% of BMT-treated patients.

Compared with individuals without CML, TKI-treated patients had greater odds of poor general health (adjusted odds ratio [aOR], 4.43; 95% CI, 1.8-10.7), functional impairment (aOR, 2.84; 95% CI, 1.4-6.0), and activity limitations (aOR, 3.37; 95% CI, 1.7-6.7). They were also more likely to experience pre-frailty or frailty (aOR, 3.71; 95% CI, 1.7-8.1).

Health outcomes were largely comparable between the TKI and BMT cohorts. However, TKI-treated patients had approximately twice the odds of reporting activity limitations (aOR, 2.2; 95% CI, 1.1-4.5).

Findings Highlight Survivorship Needs in CML

The health domains examined have important implications for long-term CML care. The researchers noted that functional impairment and activity limitations can affect patients’ ability to perform everyday tasks and may signal risks for falls, social isolation, hospitalization, and nursing home admission.

Fatigue alone did not appear to explain the increased activity limitations. Fatigue was reported by 35.5% of TKI-treated patients and 32.1% of BMT-treated patients.

However, TKI-treated patients with activity limitations were twice as likely to have congestive heart failure as BMT-treated patients with activity limitations. The researchers suggested that the higher prevalence of congestive heart failure among TKI-treated patients may have contributed to this difference.

Health impairment also did not differ substantially according to TKI generation after adjustment for severe or life-threatening comorbidities.

Long-Term Monitoring May Help Address Health Impairment

The findings suggest that improved CML survival does not necessarily eliminate long-term health challenges associated with the disease and its treatment. Monitoring general health, functional ability, activity limitations, and frailty may therefore be important components of survivorship care for patients receiving long-term TKI therapy.

The researchers emphasized that these outcomes are particularly relevant to patients’ priorities surrounding treatment goals and quality of life.

“These findings inform a need for long-term monitoring and development of risk mitigation strategies to improve the health status as a treatment goal in CML care,” the authors concluded.

Long-term TKI-treated CML survivors experienced substantially more health impairment than individuals without CML and had health outcomes generally comparable to BMT survivors. The findings support greater attention to functional health and risk mitigation as survival continues to improve for patients with CML.

Reference

Bhatia S, Men Q, Hageman L, et al. Health status impairments in tyrosine kinase inhibitor-treated chronic myeloid leukemia patients versus blood or marrow transplant survivors and non-cancer controls. Leukemia. 2026. doi:10.1038/s41375-026-03123-w