Abstract
BackgroundMost patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs) will relapse if treatment is withdrawn, but various trials have recently demonstrated that a significant proportion of patients who achieved a stable and deep molecular response (DMR) can stop therapy without relapsing. However, most information on treatment cessation was obtained from clinical trials with strict recruiting criteria.MethodsWe evaluated the outcome of 25 patients with CML that discontinued TKI therapy in our institute in real-world clinical practice.ResultsOf the 25 patients, 76% discontinued therapy in sustained deep molecular response (SDMR) and 24% were in unsustained DMR (UDMR). Discontinuation of therapy due to adverse effects was observed in 5 and 50% of the patients in the SDMR and UDMR groups, respectively. After TKI discontinuation, patients were followed for a median of 24 months. At the time of this analysis, 56% patients had a molecular relapse after a median of 4 months. SDMR and longer treatment duration were associated with lower probability of molecular relapse: 25% in SDMR patients with TKI treatment > 96 months and 85% in UDMR patients with TKI treatment ≤96 months. All relapsed patients promptly resumed TKI therapy and regained at least major molecular response (MMR).ConclusionsOur results suggest that TKI discontinuation is safe outside clinical trials and particularly effective in CML patients who are in SDMR with longer TKI treatment duration.
Highlights
Most patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs) will relapse if treatment is withdrawn, but various trials have recently demonstrated that a significant proportion of patients who achieved a stable and deep molecular response (DMR) can stop therapy without relapsing
Our data show that 44% of the patients remained in Treatment-free remission (TFR) at 12 months, with an estimated survival without molecular relapse (SWMR) of 45.4%, a value lower than that observed in clinical trials that used major molecular response (MMR) loss as a trigger to restart TKI therapy, which is around 50–60% [12,13,14]
Supporting this hypothesis, we found that a duration of TKI therapy both, over 60 months (5 years) and 96 months (8 years), was significantly associated with a lower probability of molecular relapse after TKI discontinuation: 45 and 38% in the group of patients treated with TKI > 60 months and TKI > 96 months, respectively
Summary
Most patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs) will relapse if treatment is withdrawn, but various trials have recently demonstrated that a significant proportion of patients who achieved a stable and deep molecular response (DMR) can stop therapy without relapsing. In the last few years, several clinical discontinuation trials have demonstrated that 40–60% of chronic phase CML patients (CP-CML) who have achieved a stable deep molecular response (DMR), defined as a sustained molecular response of at least 4.5 (MR4.5), can stop therapy without relapsing [reviewed in 9,10]. In addition to DMR, other variables that have been associated with a successful treatment-free remission (TFR) include low Sokal risk group at diagnosis, chronicphase patients, optimal response to TKI therapy, longer duration of TKI therapy (> 8 years), and longer duration of DMR (> 2 years) [9]. We retrospectively aimed to assess persistence of TFR in 25 CML patients treated at our institution that discontinued therapy due to several causes, including DMR and TKI intolerance, and to identify factors that could be associated with TFR
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