Contributions
Abstract: PB1948
Type: Publication Only
Background
The introduction of the tyrosine kinase inhibitors(TKIs) into clinical practice has strikingly improved survival and remission rates for chronic phase-chronic myeloid leukemia(CP-CML) patients. An emerging goal of TKIs therapy is to achieve sustained deep molecular response. It has been consistently shown that early molecular response is associated with positive long-term outcome concerning overall survival and progression-free survival in CML patients.
Aims
The aim of this study was to investigate long-term outcomes regarding remission rates and survival in unselected group of CP-CML patients initially treated with imatinib.
Methods
This is a retrospective analysis single centre database of CP-CML patients treated with first-line imatinib 400mg daily since diagnosis and followed between August 2006 and August 2017. Patients have been analysed in intention to treat. The chronic, accelerated or blastic disease phase(CP, AP, BP) were defined according to the ELN criteria. The risk scores were calculated according to the Sokal, Euro and EUTOS formulations. Cytogenetic and molecular responses were defined according to ELN definitions and followed the procedures as described elsewhere. Cumulative incidences of treatment response were calculated under consideration of competing risks defined as progression of disease to AP, BP or death. From date of imatinib initiation, overall survival(OS) was calculated until death at any time and for any reason; progression-free survival(PFS) was calculated until progression to AP or BC at any time; event-free survival(EFS) was calculated until death, progression to AP or BP, ELN failure on imatinib or imatinib treatment discontinuation for any cause.
Results
In total 102 patients were eligible for analysis, with a median duration of therapy of 58.8(6-132) months, of which 54(52.9%) were female, with median age of 55.3(18-78) years at imatinib initiation. EUTOS score was high in 16.7% of patients. The cumulative incidence of CCyR was 69.6%(95% Cl: 66-75%) at 12 months and 82.5%(95% Cl: 79-85%) at 5 years. The cumulative incidence of MMR was 48%(95% Cl: 45-52%) of evaluable patients at 12 months, and 73.3%(95% Cl: 70-76%) at 5 years. The cumulative incidence of MR4 was 27.5%(95% Cl: 24-32%) at 24 months and 56.9%(95% Cl: 53-59%) at 5 years. Median-time to achieve MMR and MR4.0 was 1.7 and 2.8 years respectively. In the multivariate Cox model analysis, MMR at 12 months was predictive for PFS(p=0.001) and OS(p=0.001) but not for EFS(p=0.271), unlike that MR4 at 24 months was predictive for EFS(p=0.003) and PFS(p=0.011) but not for OS(p=0.505). The estimated EFS rates were 76% at 2 years, 60% at 5 years and 45% at 8 years, PFS rates were 97.1% at 2 years, 95.1% at 5 years and 92.2% at 8 years, OS rates were 98% at 2 years, 87.3% at 5 years and 82.4% at 8 years. At last follow-up, after a median of 64.5(6-132) months, 68(66.7%) patients were still on imatinib, while 25(24.5%) have been switched to 2nd TKIs nilotinib for resistance in 19(76%) or intolerance in 6(24%) cases. Overall, at latest follow-up, 16.7% patients died, of which 47.1% because of CML progression and 52.9% from other causes.
Conclusion
Analysis of this CML patients’ cohort initially treated with imatinib, consistently has been confirming high rates of remission and survival and low rates of disease progression. Subsequently, imatinib has been continuing to provide an excellent long-term treatment responses and survival outcome because more than half of patients achieved a stable deep molecular response that gives the opportunity for treatment-free strategy.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Chronic myeloid leukemia, imatinib, Outcome
Abstract: PB1948
Type: Publication Only
Background
The introduction of the tyrosine kinase inhibitors(TKIs) into clinical practice has strikingly improved survival and remission rates for chronic phase-chronic myeloid leukemia(CP-CML) patients. An emerging goal of TKIs therapy is to achieve sustained deep molecular response. It has been consistently shown that early molecular response is associated with positive long-term outcome concerning overall survival and progression-free survival in CML patients.
Aims
The aim of this study was to investigate long-term outcomes regarding remission rates and survival in unselected group of CP-CML patients initially treated with imatinib.
Methods
This is a retrospective analysis single centre database of CP-CML patients treated with first-line imatinib 400mg daily since diagnosis and followed between August 2006 and August 2017. Patients have been analysed in intention to treat. The chronic, accelerated or blastic disease phase(CP, AP, BP) were defined according to the ELN criteria. The risk scores were calculated according to the Sokal, Euro and EUTOS formulations. Cytogenetic and molecular responses were defined according to ELN definitions and followed the procedures as described elsewhere. Cumulative incidences of treatment response were calculated under consideration of competing risks defined as progression of disease to AP, BP or death. From date of imatinib initiation, overall survival(OS) was calculated until death at any time and for any reason; progression-free survival(PFS) was calculated until progression to AP or BC at any time; event-free survival(EFS) was calculated until death, progression to AP or BP, ELN failure on imatinib or imatinib treatment discontinuation for any cause.
Results
In total 102 patients were eligible for analysis, with a median duration of therapy of 58.8(6-132) months, of which 54(52.9%) were female, with median age of 55.3(18-78) years at imatinib initiation. EUTOS score was high in 16.7% of patients. The cumulative incidence of CCyR was 69.6%(95% Cl: 66-75%) at 12 months and 82.5%(95% Cl: 79-85%) at 5 years. The cumulative incidence of MMR was 48%(95% Cl: 45-52%) of evaluable patients at 12 months, and 73.3%(95% Cl: 70-76%) at 5 years. The cumulative incidence of MR4 was 27.5%(95% Cl: 24-32%) at 24 months and 56.9%(95% Cl: 53-59%) at 5 years. Median-time to achieve MMR and MR4.0 was 1.7 and 2.8 years respectively. In the multivariate Cox model analysis, MMR at 12 months was predictive for PFS(p=0.001) and OS(p=0.001) but not for EFS(p=0.271), unlike that MR4 at 24 months was predictive for EFS(p=0.003) and PFS(p=0.011) but not for OS(p=0.505). The estimated EFS rates were 76% at 2 years, 60% at 5 years and 45% at 8 years, PFS rates were 97.1% at 2 years, 95.1% at 5 years and 92.2% at 8 years, OS rates were 98% at 2 years, 87.3% at 5 years and 82.4% at 8 years. At last follow-up, after a median of 64.5(6-132) months, 68(66.7%) patients were still on imatinib, while 25(24.5%) have been switched to 2nd TKIs nilotinib for resistance in 19(76%) or intolerance in 6(24%) cases. Overall, at latest follow-up, 16.7% patients died, of which 47.1% because of CML progression and 52.9% from other causes.
Conclusion
Analysis of this CML patients’ cohort initially treated with imatinib, consistently has been confirming high rates of remission and survival and low rates of disease progression. Subsequently, imatinib has been continuing to provide an excellent long-term treatment responses and survival outcome because more than half of patients achieved a stable deep molecular response that gives the opportunity for treatment-free strategy.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Chronic myeloid leukemia, imatinib, Outcome