P50-3 Treatment-free remission in e19a2 BCR-ABL1 chronic myeloid leukemia

Abstract

Chronic myeloid leukemia (CML) has become a chronic disease, for which the chronic phase is manageable with tyrosine kinase inhibitor (TKI) therapy. Several TKI discontinuation studies in patients with durable deep molecular response demonstrate that stopping TKI therapy is feasible, and this situation is called treatment-free remission (TFR). In present, The NCCN guidelines and the ESMO guidelines provide guidelines for TKI discontinuation. In these guidelines, quantifiable BCR-ABL1 transcript and monitoring using international scale (IS) are involved in the criteria of TKI discontinuation. Because IS can quantify only e13a2 or e14a2 transcripts, other transcript variants does not match the TFR criteria. Here we describe an e19a2-positive CML patient who maintain TFR. A 77-year old woman was diagnosed e19a2-positive CML, and achieved deep molecular response by nilotinib. Since 66 months of nilotinib treatment, e19a2 transcript has been undetected. Since 84 months of nilotinib treatment, she has refused subsequent medication for CML and therefore careful monitoring by QT-PCR has been done. By 40 months since nilotinib discontinuation, she has been well without any sign of withdrawal syndrome and e19a2 transcript has been undetected. In literature search, there is no report of the e19a2-positive CML who obtained TFR. As in the case we presented here, TFR may be achievable in patients with transcript variants other than e13a2 or e14a2. The problem to be solved is the standardization of transcript quantification. Both the ELN guidelines and the NCCN guidelines are created on the premise that they are monitored by the IS method which can only use for e13a2 or e14a2 transcript, meaning there is no treatment guidelines for other variants. Establishing standardized quantification of variant transcripts based on global clinical trials may contribute to prepare the treatment guideline including TFR as similar to e13a2 or e14a2 transcript.