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Long term CML follow up clinical trials are quite important tool to monitor the late or new adverse side effects as well as to conform the efficacy in the long run of the drug tested. However, there are not so many examples on CML outside the IRIS trial. Recently, Kantarjian and collaborators had published the 10 years follow up on the ENESTnd trial that compared the use of two doses of nilotinib (300md bid and 400 mg bid) against imatinib (400mg qd). Once again, the study showed a higher cumulative molecular response rates (MMR: 77% vs 79% vs 62% and MR4.5:61% vs61% vs 39%) that translated in a higher proportion of patient candidates for TFR (48% vs 47% vs 29%). Furthermore, nilotinib was associated to lower rates of disease progression compare with imatinib. As previously described there were no differences in terms of PFS or OS between the three arms. In terms of toxicity, although the overall adverse effects were similar, a higher incidence of cardiovascular events were reported (16% vs 23% vs 3%). The incidence of these CVE on the nilotinib arm continue to occur at the same rate each year and were more associated with high and intermediate Framingham risk. Overall, the trial supports the use of nilotinib 300mg twice daily as front line therapy for CML for optimal long terms outcomes with a positive benefit-risk in the context of TFR as treatment goal.
One of the important aspects of the CVE secondary to second generation TKIs is the identification of high-risk populations as well as biomarkers that may help to prevent these episodes. In this regard, Italian investigators recently published a study of 369 patients treated with nilotinib where, besides stratification by the new coronary risk evaluation (SCORE), they measure the lipids levels at various times point since the initiation of therapy and identify cholesterol greater than 200mg/dL and LDL greater than 70 mg/dL as predictors factor for increased risk of CVE as well as a high SCORE risk. The authors suggest an aggressive follow up on lipids levels in patients taking nilotinib and the incorporation of cholesterol lowering medications.
Although the incidence of CVE has been more classically associated with nilotinib and ponatinib, more recent evidence suggests that the use of second generation TKIs in general can increase the risk of CVE in CML patients in comparison with the general population; however, it is hard to study the contribution of the disease itself. Leong and collaborators recently published a very large retrospective analysis of more than 4,000 CML patients that were age and sex matched with 42,000 controls without CML, showing that the incidence of these events is higher before and after the introduction of TKIs in 2001.
Javier Pinilla-Ibarz, MD, PhD
Senior Member
Lymphoma Section Head and
Director of Immunotherapy
Malignant Hematology Department
H. Lee Moffitt Cancer Center & Research Institute
Long term CML follow up clinical trials are quite important tool to monitor the late or new adverse side effects as well as to conform the efficacy in the long run of the drug tested. However, there are not so many examples on CML outside the IRIS trial. Recently, Kantarjian and collaborators had published the 10 years follow up on the ENESTnd trial that compared the use of two doses of nilotinib (300md bid and 400 mg bid) against imatinib (400mg qd). Once again, the study showed a higher cumulative molecular response rates (MMR: 77% vs 79% vs 62% and MR4.5:61% vs61% vs 39%) that translated in a higher proportion of patient candidates for TFR (48% vs 47% vs 29%). Furthermore, nilotinib was associated to lower rates of disease progression compare with imatinib. As previously described there were no differences in terms of PFS or OS between the three arms. In terms of toxicity, although the overall adverse effects were similar, a higher incidence of cardiovascular events were reported (16% vs 23% vs 3%). The incidence of these CVE on the nilotinib arm continue to occur at the same rate each year and were more associated with high and intermediate Framingham risk. Overall, the trial supports the use of nilotinib 300mg twice daily as front line therapy for CML for optimal long terms outcomes with a positive benefit-risk in the context of TFR as treatment goal.
One of the important aspects of the CVE secondary to second generation TKIs is the identification of high-risk populations as well as biomarkers that may help to prevent these episodes. In this regard, Italian investigators recently published a study of 369 patients treated with nilotinib where, besides stratification by the new coronary risk evaluation (SCORE), they measure the lipids levels at various times point since the initiation of therapy and identify cholesterol greater than 200mg/dL and LDL greater than 70 mg/dL as predictors factor for increased risk of CVE as well as a high SCORE risk. The authors suggest an aggressive follow up on lipids levels in patients taking nilotinib and the incorporation of cholesterol lowering medications.
Although the incidence of CVE has been more classically associated with nilotinib and ponatinib, more recent evidence suggests that the use of second generation TKIs in general can increase the risk of CVE in CML patients in comparison with the general population; however, it is hard to study the contribution of the disease itself. Leong and collaborators recently published a very large retrospective analysis of more than 4,000 CML patients that were age and sex matched with 42,000 controls without CML, showing that the incidence of these events is higher before and after the introduction of TKIs in 2001.
Javier Pinilla-Ibarz, MD, PhD
Senior Member
Lymphoma Section Head and
Director of Immunotherapy
Malignant Hematology Department
H. Lee Moffitt Cancer Center & Research Institute
Long term CML follow up clinical trials are quite important tool to monitor the late or new adverse side effects as well as to conform the efficacy in the long run of the drug tested. However, there are not so many examples on CML outside the IRIS trial. Recently, Kantarjian and collaborators had published the 10 years follow up on the ENESTnd trial that compared the use of two doses of nilotinib (300md bid and 400 mg bid) against imatinib (400mg qd). Once again, the study showed a higher cumulative molecular response rates (MMR: 77% vs 79% vs 62% and MR4.5:61% vs61% vs 39%) that translated in a higher proportion of patient candidates for TFR (48% vs 47% vs 29%). Furthermore, nilotinib was associated to lower rates of disease progression compare with imatinib. As previously described there were no differences in terms of PFS or OS between the three arms. In terms of toxicity, although the overall adverse effects were similar, a higher incidence of cardiovascular events were reported (16% vs 23% vs 3%). The incidence of these CVE on the nilotinib arm continue to occur at the same rate each year and were more associated with high and intermediate Framingham risk. Overall, the trial supports the use of nilotinib 300mg twice daily as front line therapy for CML for optimal long terms outcomes with a positive benefit-risk in the context of TFR as treatment goal.
One of the important aspects of the CVE secondary to second generation TKIs is the identification of high-risk populations as well as biomarkers that may help to prevent these episodes. In this regard, Italian investigators recently published a study of 369 patients treated with nilotinib where, besides stratification by the new coronary risk evaluation (SCORE), they measure the lipids levels at various times point since the initiation of therapy and identify cholesterol greater than 200mg/dL and LDL greater than 70 mg/dL as predictors factor for increased risk of CVE as well as a high SCORE risk. The authors suggest an aggressive follow up on lipids levels in patients taking nilotinib and the incorporation of cholesterol lowering medications.
Although the incidence of CVE has been more classically associated with nilotinib and ponatinib, more recent evidence suggests that the use of second generation TKIs in general can increase the risk of CVE in CML patients in comparison with the general population; however, it is hard to study the contribution of the disease itself. Leong and collaborators recently published a very large retrospective analysis of more than 4,000 CML patients that were age and sex matched with 42,000 controls without CML, showing that the incidence of these events is higher before and after the introduction of TKIs in 2001.