Molecular Response Maintained With Intermittent Tyrosine Kinase Inhibitor Regimen in Patients With CML

Molecular response (MR) in patients with chronic myeloid leukemia (CML) who were not eligible for treatment discontinuation was maintained with a long-term tyrosine kinase inhibitor (TKI) regimen of 1 month on/1 month off. These findings, from an interim analysis of a phase III, randomized study, were published in Cancer Medicine.

Many patients receiving TKIs for CML who do not achieve a stable deep molecular response and are not eligible for treatment discontinuation may be candidates for intermittent treatment. The OPTkIMA study sought to evaluate if a progressive de-escalation of TKI therapy would maintain molecular response and improve health-related quality of life (HRQOL).

For this study, 185 patients with CML (age, median 71 years [range, 60 to 89]) were recruited for the OPTkIMA study at 26 centers in Italy in 2015. A continuous 1 month on/off TKI treatment plan for 3 years (fixed plan; 99 patients) was compared with a progressive plan comprised of 1 month on/off for 1 year; 1 month on, 2 months off for 1 year; and 1 month on, 3 months off for 1 year (86 patients). Patients were assessed for molecular response (MR) and by health-related quality of life (HRQOL).

After the first year of 1 month on/off TKI therapy, molecular response was maintained in 81% of patients. Patients who had been in MR for more than 3 years were less likely to lose MR (hazard ratio [HR], 0.23; 95% CI, 0.10-0.61; P =.0025).

A total of 119 patients continued therapy into year 2 (59 in the fixed group; 46 in the progressive group). Molecular response was maintained through the second year.

Symptoms of diarrhea (P =.022) and nausea (P =.006) improved during the first months of TKI therapy, but fatigue was exacerbated over time (P =.022). Women had lower HRQOL scores compared with men (P =.001).

This study was limited by its low sample sizes and retention rates.

This intermittent analysis suggested 1 month on/off TKI therapy was effective at maintaining molecular response among most patients with CML who were ineligible for treatment discontinuation.


Malagola M, Iurlo A, Abruzzese E, et al. Molecular response and quality of life in chronic myeloid leukemia patients treated with intermittent TKIs: First interim analysis of OPTkIMA study. Cancer Med. Published online February 16, 2021. doi:10.1002/cam4.3778.