Contributions
Abstract: PB1963
Type: Publication Only
Background
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. In addition to DMR, other variables that have been associated with a successful treatment-free remission (TFR) include low Sokal risk group at diagnosis, chronic-phase disease, optimal response to TKI therapy, longer duration of TKI therapy (> 8 years), and longer duration of DMR (> 2 years). In all published trials, the majority of patients who experienced relapse did so within 6 months of TKI cessation and, with the exception of one case that progressed to blast crisis, relapsed patients remained responsive to retreatment and regained at least a major molecular response (MMR). However, most information on treatment cessation was obtained from clinical trials with strict recruiting criteria.
Aims
In this study, we 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.
Methods
The medical records of all CP-CML patients who were treated with TKIs in our institution between 1997 and 2015 were reviewed and clinical and laboratory data was collected. The eligibility criteria were CP-CML, treated with any of the first-line approved TKIs (Imatinib, Nilotinib, and Dasatinib), that discontinued TKI therapy due to any reason. Only patients with typical transcripts [that is, b3a2 (e14a2) and/or b2a2 (e13a2)], determined by RT-PCR at the time of diagnosis were included.
Results
We evaluated the outcome of 25 patients with CML that discontinued TKI therapy in our institute due to any reason. Of them, 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 20 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 patients and 85% in UDMR patients with TKI treatment ≤96 months. All relapsed patients promptly resumed TKI therapy and regained at least a major molecular response (MMR).
Conclusion
Our results suggest that TKI discontinuation is safe outside clinical trials and particularly effective in CML patients who are in SDMR with longer duration of TKI treatment.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Chronic myeloid leukemia, Molecular relapse, Molecular remission, Tyrosine kinase inhibitor
Abstract: PB1963
Type: Publication Only
Background
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. In addition to DMR, other variables that have been associated with a successful treatment-free remission (TFR) include low Sokal risk group at diagnosis, chronic-phase disease, optimal response to TKI therapy, longer duration of TKI therapy (> 8 years), and longer duration of DMR (> 2 years). In all published trials, the majority of patients who experienced relapse did so within 6 months of TKI cessation and, with the exception of one case that progressed to blast crisis, relapsed patients remained responsive to retreatment and regained at least a major molecular response (MMR). However, most information on treatment cessation was obtained from clinical trials with strict recruiting criteria.
Aims
In this study, we 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.
Methods
The medical records of all CP-CML patients who were treated with TKIs in our institution between 1997 and 2015 were reviewed and clinical and laboratory data was collected. The eligibility criteria were CP-CML, treated with any of the first-line approved TKIs (Imatinib, Nilotinib, and Dasatinib), that discontinued TKI therapy due to any reason. Only patients with typical transcripts [that is, b3a2 (e14a2) and/or b2a2 (e13a2)], determined by RT-PCR at the time of diagnosis were included.
Results
We evaluated the outcome of 25 patients with CML that discontinued TKI therapy in our institute due to any reason. Of them, 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 20 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 patients and 85% in UDMR patients with TKI treatment ≤96 months. All relapsed patients promptly resumed TKI therapy and regained at least a major molecular response (MMR).
Conclusion
Our results suggest that TKI discontinuation is safe outside clinical trials and particularly effective in CML patients who are in SDMR with longer duration of TKI treatment.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Chronic myeloid leukemia, Molecular relapse, Molecular remission, Tyrosine kinase inhibitor