Molecular Relapse After a Second Treatment-Free Remission Attempt Following Asciminib in Chronic Myeloid Leukemia: A Case Report.

Treatment-free remission (TFR) has become an important therapeutic goal in chronic myeloid leukemia (CML). Although the outcomes of TFR following adenosine triphosphate (ATP)-competitive tyrosine kinase inhibitors (TKIs) have been established, data on TFR after asciminib discontinuation remain limited. In this study, we report the case of a man in his 60s with chronic-phase CML who experienced molecular relapse 8 months after a second TFR attempt following asciminib treatment. The patient was diagnosed with CML approximately 15 years earlier and achieved deep molecular response 4.5 (MR4.5), representing a 4.5-log reduction in BCR::ABL1 transcripts, with first-line imatinib. After the first TFR attempt, major molecular response (MMR) was lost, and ponatinib was initiated but discontinued because of cerebral infarction. Asciminib was subsequently introduced as third-line therapy at a dose of 40 mg twice daily, and BCR::ABL1 transcripts remained undetectable for more than 3 years. Based on the sustained deep molecular response and patient preference, asciminib was discontinued. Eight months after discontinuation, however, loss of MR4.0 (BCR::ABL1 > 0.01% IS) was detected. This threshold was used to guide treatment reinitiation, rather than waiting for loss of MMR as recommended by the ELN guidelines, in the view of the clinical context of a second TFR attempt following prior failure. Imatinib was reintroduced, leading to the reachievement of a deep molecular response. This case underscores the importance of careful patient selection and long-term molecular monitoring following TFR attempts, including those involving novel TKIs such as asciminib.