Incidences of Deep Molecular Responses and Treatment-Free Remission in de Novo CP-CML Patients

SIMPLE SUMMARY: Tyrosine kinase inhibitors (TKI) can be safely discontinued in chronic myeloid leukemia patients. Achieving a sustained deep molecular response (DMR) before stop is recommended. Currently, the proportion of patients who achieve a sustained DMR remains to be determined. Based on the follow-up of 398 patients over a ten-years period, we evaluate that 46% of them have achieved a sustained DMR. Gender, BCR-ABL1 transcript type, and disease risk scores were significantly associated with the probability of achieving a DMR. 95/398 (24%) patients stopped TKI with a probability of maintaining molecular reponse without TKI resumption of 47% at 48 months after stop. In this study, TKI duration before stop and second (nilotinib, dasatinib, bosutinib) generation frontline TKI compared to imatinib were significantly associated with a lower risk of molecular relapse after stop in patients who have achieved a sustained DMR. ABSTRACT: Background: Tyrosine Kinase Inhibitors (TKIs) discontinuation in patients who had achieved a deep molecular response (DMR) offer now the opportunity of prolonged treatment-free remission (TFR). Patients and Methods: Aims of this study were to evaluate the proportion of de novo chronic-phase chronic myeloid leukemia (CP-CML) patients who achieved a sustained DMR and to identify predictive factors of DMR and molecular recurrence-free survival (MRFS) after TKI discontinuation. Results: Over a period of 10 years, 398 CP-CML patients treated with first-line TKIs were included. Median age at diagnosis was 61 years, 291 (73%) and 107 (27%) patients were treated with frontline imatinib (IMA) or second- or third-generation TKIs (2–3G TKI), respectively. With a median follow-up of seven years (range, 0.6 to 13.8 years), 182 (46%) patients achieved a sustained DMR at least 24 months. Gender, BCR-ABL1 transcript type, and Sokal and ELTS risk scores were significantly associated with a higher probability of sustained DMR while TKI first-line (IMA vs. 2–3G TKI) was not. We estimate that 28% of CML-CP would have been an optimal candidate for TKI discontinuation according to recent recommendations. Finally, 95 (24%) patients have entered in a TFR program. MRFS rates at 12 and 48 months were 55.1% (95% CI, 44.3% to 65.9%) and 46.9% (95% CI, 34.9% to 58.9%), respectively. In multivariate analyses, first-line 2–3G TKIs compared to IMA and TKI duration were the most significant factors of MRFS. Conclusions: Our results suggest that frontline TKIs have a significant impact on TFR in patients who fulfill the selection criteria for TKI discontinuation.