Pb1962: influence of transcript types in sustained deep molecular response (sdmr) and treatment-free remission (tfr) in chronic phase-chronic myeloid leukemia (cp-cml) patients treated with tki

Topic: 7. Chronic myeloid leukemia - Biology & Translational Research Background: Chronic myeloid leukemia (CML) is characterized by BCR::ABL1 fusion gene with e13a2 and e14a2 as the most frequent transcript types. Imatinib (IM), dasatinib (DA) and nilotinib (NI) are the standard of care in patients with chronic phase CML (CP-CML). Lifelong tyrosine-kinase inhibitors (TKI) treatment is associated with adverse events and high cost. Thus, the current goal is to achieve a sustained deep molecular response (sDMR) in order to discontinue TKI treatment. Approximately 50% of patients with sDMR can remain in the so-called treatment-free remission (TFR) phase after discontinuing TKI treatment. Therefore, there is a need to identify factors at diagnosis that will be associated with the acquisition of sDMR and maintenance of TFR. There are few studies about the effect of BCR::ABL1 transcript type on TFR, but all of them point to an association between longer TFR in CP-CML patients with e14a2 that discontinued IM in front-line. Aims: The aim of the present study was to evaluate the effect of the BCR::ABL1 transcript type on DMR achievement and TFR in a series of CP-CML patients treated with IM or 2G-TKI as first-line treatment. Methods: Peripheral blood (PB) and bone marrow (BM) (when applicable) were obtained at diagnosis and during the follow-up of 156 IM and 39 2G-TKI treated patients. Patients were analyzed according to the 2020 European Leukemia Net (ELN) guidelines. During TFR, patients were monitored monthly during the first 6 months and every 6 weeks later. Patients who had changed to other TKI prior to DMR acquisition and TKI discontinuation were not eligible. The DMR was defined as the achievement of molecular response 4.0 (MR4.0) or 4.5 (MR4.5). TFR was defined as the time from TKI discontinuation until loss of major molecular response (MMR), restart of TKI treatment, progression, or death from any cause. The statistical R software (version 4.2.2) were used for all analyses. Two-sided P values<0.05 were considered as statistically significant. Results: No statistically significant differences were observed between e13a2 and e14a2 groups achivement of sDMR, not only in patients treated with first-line IM (p=0.547) but also with first-line 2G-TKI (p=0.501). There were no statistical differences on TFR according to transcript types and the type of treatment received (p=0.530 and p=0.800). However, we analyzed the IM or 2G-TKI treatment duration and the sDMR duration before discontinuation and we could stablish a significant cut-off of IM treatment of 119 months (p=0.009) and 78 months for 2G-TKI treatment (p=0.049), and a significant cut-off of 108 months for sDMR during IM treatment (p=0.004) previous to discontinuation in those patients with less probability of relapsed after discontinuation. With these cut-offs, when we re-analyzed the TFR we observed a better TFR in those patients with e14a2 and more than 119 months of IM treatment (p=0.040) and also in those patients with e14a2 and more than 108 months in sDMR (p=0.031). Sample size did not allow us to perform the same analysis on 2G-TKI treated patients.Summary/Conclusion: Treatment duration has to be considered for a better discontinuation in both IM and 2G-TKI first-line treated CML patients. sDMR duration and transcript type have also an influence in TFR in patients treated with IM. More patients discontinuing 2G-TKI are needed to stablish a correlation between TFR and transcript types. Keywords: Chronic myeloid leukemia, treatment-free remission, BCR-ABL, Molecular response