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

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.

Successful tyrosine kinase inhibitor discontinuation outside clinical trials — data from the population‐based Swedish chronic myeloid leukaemia registry

“…In summary, our results from a population‐based study show that TKI discontinuation in CML in clinical practice is common and feasible and as successful as when performed within a clinical trial. Our findings are also in line with previous reports of discontinuation of TKI therapy in clinical routine that patients treated with second‐generation TKI achieve a higher TFR rate 19,27 …”

“…However, basing the estimation on cumulative incidences of DMR tends to overestimate the proportion in stable DMR. In a recent French study of patients treated with TKI outside of clinical trials, cumulative incidence of MR4.0 was 72%, while sustained MR4.0 was reached by 46% after a median follow‐up time of seven years 27 . In addition, a prerequisite for reaching this optimal TFR rate is a consensus between individual patients and treating physicians that TFR is the goal of the treatment.…”

“…Our findings are also in line with previous reports of discontinuation of TKI therapy in clinical routine that patients treated with second-generation TKI achieve a higher TFR rate. 19,27…”

Relevance of treatment‐free remission recommendations in chronic phase chronic leukemia patients treated with frontline tyrosine kinase inhibitors

“…Baseline characteristics of the study population have been previously reported 13 . Briefly, the median age at diagnosis was 61.7 years (range, 18.6 to 90.2 years), 58% of patients were male, and Sokal and ELTS risk scores were high in 19% and 13% of them, respectively.…”

“…Based on the hypothesis that first‐line TKI type (IMA vs 2‐3G TKI) may have an impact on MRFS, 13 we next analyzed the impact of first‐line TKI together with the selection criteria proposed by recommendations. None of the 95 patients who discontinued TKI in this study received frontline or thereafter third generation TKI.…”