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In a comprehensive and detailed analysis, Ochi et al evaluated the genetic alterations in 136 blast crisis (BC) and 148 chronic phase (CP) samples from 216 patients with chronic myeloid leukemia (CML) by exome and targeted sequencing. The number of genetic alterations increased during CP to BC progression with a mean of 5.3 nonsynonymous single-nucleotide variants acquired. One or more genetic abnormalities are found in 126 (92.6%) out of the 136 BC patients. As expected, the lineage of the BC and prior use of tyrosine kinase inhibitors (TKIs) correlate with distinct molecular profiles. TKIs markedly suppressed the number of genetic alterations increase during the transition from CP to BC. Notably, genetic alterations such AXL1 mutations complex CNAs, i(17q), and +21, rather than clinical variables, contribute to a better prediction of BC prognosis in early therapy with TKI in CP.
Switching to a second generation TKI with the goal of obtaining a deeper response and therefore a chance for treatment-free remission (TFR), is an option for certain patients and has been investigated in a few trials. ENEStop may be the most popular and Hughes et al had updated the 5 years follow up in a recent publication. The study includes patients with chronic-phase chronic myeloid leukemia (CML-CP) who achieved sustained deep molecular response only after switching from imatinib to nilotinib and TFR was attempted by 126 patients following 1 year of nilotinib consolidation phase. At 5 years, the rate of successful TFR and overall survival was 42.9% and 95.9%, respectively. Of 59 patients reinitiating nilotinib, 98.3% of patients regained major molecular response. Overall, AEs increased in nilotinib reinitiation vs. consolidation phase including cardiovascular (CV) adverse events (AEs) as patients had a long duration of exposure for nilotinib.
After several publications and recommendations by NCCN and ELN, the optimal cut-off values of the duration of MR4 and deeper responses remain unresolved. Kim et al reported a large study of 131 patients enrolled into the Canadian TKI discontinuation study and evaluated the molecular relapse-free survival (mRFS) at 12 months after imatinib discontinuation. Based on this analysis they propose 6 years with imatinib treatment duration as the shortest imatinib duration- a superior success versus less than 6 years (61.8% vs. 36.0%; P = .01). Also a MR4 duration of 4.5 years or longer vs. less than 4.5 years (64.2% vs. 41.9%; P = .003) was associated with a superior molecular relapse-free survival at 12 months after imatinib discontinuation.
Fatigue is a common complain of patients taking TKI and has been well reported as adverse effects in most of the CML trials. However, when evaluating fatigue, it is always difficult to understand if there are additional factors that can contribute to it. Hyland et al investigated if the use of cognitive behavioral therapy for targeted-therapy related fatigue (CBT-TTF) targeting fatigue perpetuating factors change over time. By delivering CBT via FaceTime or wait list control in CML patients with moderate or severe fatigue, they were able to see an improvement in TKI-related fatigue in CML patients through changes in behavior (sleep, activity patterns) and cognitions about fatigue and cancer.
In a comprehensive and detailed analysis, Ochi et al evaluated the genetic alterations in 136 blast crisis (BC) and 148 chronic phase (CP) samples from 216 patients with chronic myeloid leukemia (CML) by exome and targeted sequencing. The number of genetic alterations increased during CP to BC progression with a mean of 5.3 nonsynonymous single-nucleotide variants acquired. One or more genetic abnormalities are found in 126 (92.6%) out of the 136 BC patients. As expected, the lineage of the BC and prior use of tyrosine kinase inhibitors (TKIs) correlate with distinct molecular profiles. TKIs markedly suppressed the number of genetic alterations increase during the transition from CP to BC. Notably, genetic alterations such AXL1 mutations complex CNAs, i(17q), and +21, rather than clinical variables, contribute to a better prediction of BC prognosis in early therapy with TKI in CP.
Switching to a second generation TKI with the goal of obtaining a deeper response and therefore a chance for treatment-free remission (TFR), is an option for certain patients and has been investigated in a few trials. ENEStop may be the most popular and Hughes et al had updated the 5 years follow up in a recent publication. The study includes patients with chronic-phase chronic myeloid leukemia (CML-CP) who achieved sustained deep molecular response only after switching from imatinib to nilotinib and TFR was attempted by 126 patients following 1 year of nilotinib consolidation phase. At 5 years, the rate of successful TFR and overall survival was 42.9% and 95.9%, respectively. Of 59 patients reinitiating nilotinib, 98.3% of patients regained major molecular response. Overall, AEs increased in nilotinib reinitiation vs. consolidation phase including cardiovascular (CV) adverse events (AEs) as patients had a long duration of exposure for nilotinib.
After several publications and recommendations by NCCN and ELN, the optimal cut-off values of the duration of MR4 and deeper responses remain unresolved. Kim et al reported a large study of 131 patients enrolled into the Canadian TKI discontinuation study and evaluated the molecular relapse-free survival (mRFS) at 12 months after imatinib discontinuation. Based on this analysis they propose 6 years with imatinib treatment duration as the shortest imatinib duration- a superior success versus less than 6 years (61.8% vs. 36.0%; P = .01). Also a MR4 duration of 4.5 years or longer vs. less than 4.5 years (64.2% vs. 41.9%; P = .003) was associated with a superior molecular relapse-free survival at 12 months after imatinib discontinuation.
Fatigue is a common complain of patients taking TKI and has been well reported as adverse effects in most of the CML trials. However, when evaluating fatigue, it is always difficult to understand if there are additional factors that can contribute to it. Hyland et al investigated if the use of cognitive behavioral therapy for targeted-therapy related fatigue (CBT-TTF) targeting fatigue perpetuating factors change over time. By delivering CBT via FaceTime or wait list control in CML patients with moderate or severe fatigue, they were able to see an improvement in TKI-related fatigue in CML patients through changes in behavior (sleep, activity patterns) and cognitions about fatigue and cancer.
In a comprehensive and detailed analysis, Ochi et al evaluated the genetic alterations in 136 blast crisis (BC) and 148 chronic phase (CP) samples from 216 patients with chronic myeloid leukemia (CML) by exome and targeted sequencing. The number of genetic alterations increased during CP to BC progression with a mean of 5.3 nonsynonymous single-nucleotide variants acquired. One or more genetic abnormalities are found in 126 (92.6%) out of the 136 BC patients. As expected, the lineage of the BC and prior use of tyrosine kinase inhibitors (TKIs) correlate with distinct molecular profiles. TKIs markedly suppressed the number of genetic alterations increase during the transition from CP to BC. Notably, genetic alterations such AXL1 mutations complex CNAs, i(17q), and +21, rather than clinical variables, contribute to a better prediction of BC prognosis in early therapy with TKI in CP.
Switching to a second generation TKI with the goal of obtaining a deeper response and therefore a chance for treatment-free remission (TFR), is an option for certain patients and has been investigated in a few trials. ENEStop may be the most popular and Hughes et al had updated the 5 years follow up in a recent publication. The study includes patients with chronic-phase chronic myeloid leukemia (CML-CP) who achieved sustained deep molecular response only after switching from imatinib to nilotinib and TFR was attempted by 126 patients following 1 year of nilotinib consolidation phase. At 5 years, the rate of successful TFR and overall survival was 42.9% and 95.9%, respectively. Of 59 patients reinitiating nilotinib, 98.3% of patients regained major molecular response. Overall, AEs increased in nilotinib reinitiation vs. consolidation phase including cardiovascular (CV) adverse events (AEs) as patients had a long duration of exposure for nilotinib.
After several publications and recommendations by NCCN and ELN, the optimal cut-off values of the duration of MR4 and deeper responses remain unresolved. Kim et al reported a large study of 131 patients enrolled into the Canadian TKI discontinuation study and evaluated the molecular relapse-free survival (mRFS) at 12 months after imatinib discontinuation. Based on this analysis they propose 6 years with imatinib treatment duration as the shortest imatinib duration- a superior success versus less than 6 years (61.8% vs. 36.0%; P = .01). Also a MR4 duration of 4.5 years or longer vs. less than 4.5 years (64.2% vs. 41.9%; P = .003) was associated with a superior molecular relapse-free survival at 12 months after imatinib discontinuation.
Fatigue is a common complain of patients taking TKI and has been well reported as adverse effects in most of the CML trials. However, when evaluating fatigue, it is always difficult to understand if there are additional factors that can contribute to it. Hyland et al investigated if the use of cognitive behavioral therapy for targeted-therapy related fatigue (CBT-TTF) targeting fatigue perpetuating factors change over time. By delivering CBT via FaceTime or wait list control in CML patients with moderate or severe fatigue, they were able to see an improvement in TKI-related fatigue in CML patients through changes in behavior (sleep, activity patterns) and cognitions about fatigue and cancer.