Study Finds Treatment-Free Remission Not Impaired by Low-Dose TKIs for Patients with CML

Researchers found that long-term treatment-free remission was not impaired by low-dose TKI regimens for patients with chronic myeloid leukemia.

Long-term treatment-free remission was not impaired by low-dose tyrosine kinase inhibitor (TKI) regimens before TKI cessation in patients with chronic myeloid leukemia (CML), according to a retrospective study published in Cancer.

The researchers suggest enacting prospective, randomized clinical trials to analyze the probability of successful treatment-free remission for patients managed with TKI dose de-escalation strategies before TKI discontinuation.

“This study shows that the [treatment-free remission] of patients with CML who had sustained [deep molecular response] while on low-dose TKI is not compromised compared with patients who were managed with abrupt treatment cessation of full-dose TKIs,” wrote the researchers. “Moreover, the results appear independent of both dose reduction and a potential pretreatment with IFN-α.”

The results found that 61.5% of patients in the low-dose group received second-generation TKIs, and dose reduction was greater than or equal to 50% for 65.4% of patients. More, with a median follow-up of 61.5 months, treatment-free remission was 56.8% at 12 months in the full-dose TKI group and 80.8% in the low-dose group. Treatment-free remission at 60 months was 47.5% and 58.8%, respectively.

The entire cohort saw a median time to molecular recurrence from TKI discontinuation of 6.2 months. Even more, all patients achieved major molecular response after resuming TKI therapy. Overall, the results appear independent of both dose reduction and potential pretreatment with interferon-α.

“For selected patients with CML in [deep molecular response], TKI dose reduction is known to improve quality of life without affecting safety or causing loss of [major molecular response],” wrote the researchers. “To demonstrate a higher benefit of this strategy for patients with CML who are eligible for an attempt at TKI discontinuation, prospective randomized clinical trials are needed.”

The researchers retrospectively analyzed 77 patients with CML who discontinued their treatments with TKIs. Of that group, 26 patients were managed with low-dose TKIs before stopping treatment. The loss of major molecular response was considered a “trigger for restarting therapy.”

The study was limited by the retrospective style and number of patients included, which meant the study could not identify a difference in TFR between full-dose and low-dose TKI treatment approaches. More, the proportion of sustained molecular recurrence was not correlated with the degree of TKI dose reduction.

“In the present study, we retrospectively analyzed a series of patients with CML who discontinued treatment with TKIs,” wrote the researchers. “At the time of therapy cessation, the patients were treated with full-dose or low-dose TKIs (mainly for significant nonhematologic adverse events).”


Cayssials E, Torregrosa-Diaz J, Gallego-Hernanz P, et al. Low-Dose Tyrosine Kinase Inhibitors Before Treatment Discontinuation Do Not Impair Treatment-Free Remission in Chronic Myeloid Leukemia Patients: Results of a Retrospective Study. Cancer. DOI: 10.1002/cncr.32940.