TKI treatment discontinuation in chronic myeloid leukaemia feasible in clinical practice
Discontinuing the use of tyrosine kinase inhibitors (TKIs) in the treatment of patients with chronic myeloid leukaemia (CML) appears to be feasible in real-life clinical practice in the context of close molecular monitoring, a study reports.
Researchers examined the outcomes of TKI cessation in a nationwide series of 236 CML patients (median age at cessation, 61 years; 52 percent female) in deep molecular response. TKI agents used included imatinib, nilotinib, dasatinib, bosutinib and ponatinib.
The main reasons for TKI discontinuation were presence of side effects or a concomitant disease (n=66), an attempt to achieve a treatment-free remission in the absence of clinically relevant TKI toxicity (n=166), and pregnancy or planning pregnancy (n=4).
Median follow-up from treatment discontinuation was 21.5 months, and five patients died from CML-unrelated causes. TKI treatment was reinitiated due to loss of major molecular response (MMR; n=52), an increase ≥1 log in BCR-ABL transcript level without losing MMR (n=12), patient preference (n=2) and withdrawal syndrome (n=1).
The rate of treatment-free remission at 4 years was 64 percent, while cumulative incidence of molecular recurrence at 3 years was 33 percent. TKI treatment for <5 years and MR4.5 duration <4 years both showed an association with increased incidence of molecular recurrence.
None of the patients had disease progression.
Response status at last control MR4.5 in 196 patients, MR4 in 15, MMR in 14, complete cytogenetic response in 10, and other in one. Significant elevations in haemoglobin and cholesterol levels were observed following imatinib withdrawal.
The present data provide reassurance regarding the safety of TKI treatment discontinuation in real-life clinical practice in the context of close molecular monitoring, researchers said. Specifically, resolution of TKI-related toxicity might translate into a potential health improvement in CML patients.
Additional studies addressing the biological factors underlying the mechanisms of disease control after TKI treatment discontinuation are warranted, researchers added.