Observational study of chronic myeloid leukemia Italian patients who discontinued tyrosine kinase inhibitors in clinical practice

Abstract

It is judged safe to discontinue treatment with tyrosine kinase inhibitors (TKI) for chronic myeloid leukemia (CML) in experimental trials on treatment-free remission (TFR). We collected a total of 293 Italian patients with chronic phase CML who discontinued TKI in deep molecular response. Seventy-two percent of patients were on treatment with imatinib, and 28% with second generation TKI at the time of discontinuation. Median duration of treatment with the last TKI was 77 months [Interquartile Range (IQR) 54;111], median duration of deep molecular response was 46 months (IQR 31;74). Duration of treatment with TKI and duration of deep molecular response were shorter with second generation TKI than with imatinib (P<0.001). Eighty-eight percent of patients discontinued as per clinical practice, and reasons for stopping treatment were: toxicity (20%), pregnancy (6%), and shared decision between treating physician and patient (62%). After a median follow up of 34 months (range, 12-161) overall estimated TFR was 62% (95%CI: 56;68). At 12 months, TFR was 68% (95%CI: 62;74) for imatinib, 73% (95%CI: 64;83) for second generation TKI. Overall median time to restart treatment was six months (IQR 4;11). No progressions occurred. Although our study has the limitation of a retrospective study, our experience within the Italian population confirms that discontinuation of imatinib and second generation TKI is feasible and safe in clinical practice.

Figure 1.

Kaplan-Meier curves for Italian patients who discontinued tyrosine kinase inhibitor (TKI). (A) Overall population. (B) Patients who discontinued imatinib. (C) Patients who discontinued second generation TKI. Estimated treatment-free remission (TFR) is reported at 12 months for the overall population; at 12, 26 (median follow up for patients who discontinued second generation TKI), and 42 (median follow up for patients who discontinued imatinib) months for imatinib; at 12 and 26 months (median follow up for patients who discontinued second generation TKI) for second generation TKI. N: number.

Figure 2.

Tyrosine kinase inhibitor (TKI)-treatment-free remission (TFR) curves adjusted for age at discontinuation, Sokal score, line of therapy, and duration of disease.