Canterbury DHB

Treatment-free Remission – Stopping TKI Therapy

For a review of this topic, refer to Rea, D. (2020). "Handling challenging questions in the management of chronic myeloid leukemia: when is it safe to stop tyrosine kinase inhibitors?" Blood Advances 4(21): 5589-5594."

TKI discontinuation studies in patients with durable deep molecular response (DMR) demonstrate that stopping TKI therapy is feasible.

The Stop Imatinib (STIM) trial investigated the risk of relapse in patients on imatinib with ongoing CMR for >2 years who then stopped treatment. In the most recent update, 100 patients had a median follow-up of 50 months and were monitored closely for evidence of molecular relapse. Of these, 61% experienced a molecular relapse, with 95% of the events occurring within 7 months of stopping imatinib. Of patients who resumed imatinib, 55 of 57 re-achieved an undetectable BCR-ABL1 state. No patient has experienced progression of CML.

With nilotinib, at 48 weeks after stopping, 98 patients (51.6%) remained in MMR or better (primary endpoint).

Treatment discontinuation is not yet considered standard of care, but may be considered in individual patients.

The safest prerequisites for safe stopping are:

• haematologist supervision
• no atypical BCR–ABL1 transcripts found at diagnosis
• at least 5 years of TKI therapy
• achievement of MR4.5 (4.5-log reduction), and
• a stability of DMR (at least MR4 ) for at least 2 years

Less stringent criteria have been allowed in some studies, but were associated with higher molecular relapse.

Informed consent should include information on the estimated risk of recurrence, and the importance of more frequent molecular monitoring:

• monthly during the first months
• 6-weekly during the second 6 months
• then 3-monthly

See Hughes TP, Ross DM (2016),¹⁰ figure 1, page 3.

Topic Code: 533103