Contributions
Abstract: PB1524
Type: Publication Only
Session title: Chronic myeloid leukemia - Clinical
Background
There are only few descriptions available in literature about the QTc prolongation and sudden cardiac death during treatment using BCR-ABL tyrosine kinase inhibitors.
Aims
Analysis of corrected interval QT (QTc) prolongation and sudden cardiac death of patients with chronic myeloid leukemia (CML) treated with BCR-ABL tyrosine kinase inhibitors (TKI).
Methods
The study was conducted on 114 patients who received nilotinibb, dasatinib or imatinib. All the patients underwent classical ECG monitoring and 24-hour Holter ECG monitoring with measuring of QTc duration. The trial excluded patients with severe heart diseases.
Results
Conducted comparative analysis shows statistically significant greater impact of nilotinib on the duration of QTc interval compared to other tyrosine kinase inhibitors. The maximum QTc was slightly longer than in patients treated with imatinib and dazatinib already at the early and middle stages (up to 36 months), but these differences are statistically insignificant. The main differences can be seen in patients taking nilotinib over 38 months, when these differences become statistically significant: median and interquartile range in patients on nilotinib therapy were 0.46 (0.44-0.47) s, n = 17 versus 0.43 (0.42-0.44) s in the group of patients taking dazatinib or imatinib (n=23), p=0.0004. After 7 years, we found out the fate of 110 examined patients. It turned out that 4 CML patients treated with ITK died suddenly. During analysis of the obtained data, it was found that the QTc duration in the ECG of the deceased did not differ from the survivors. At the same time, the QTc in 24-hour Holter ECG monitoring of 4 patients with sudden cardiac death was statistically significant longer than in the rest: 0.48 (0.48-0.505) s (n = 4) versus 0.45 (0.43-0.46) s (n = 110) (p=0.0003). Since all of the deceased were over the age of 52, the examination results of patients of this age were studied. A similar data was found in the group of patients older than 52 years: QTc duration of patients who died from sudden cardiac death - 0.48 (0.48-0.505) s, who are currently living or died from other reasons - 0.44 (0.43-0.46) s (n=56), p=0.001. All cases of sudden cardiac death occurred on nilotinib treatment (p=0.01), and the estimation of this indicator in the group of patients older than 52 years of age shows an identical trend with lower statistical significance (p=0.05).
Conclusion
1. We have shown that in patients with CML taking nilotinib, the QTc duration is statistically significant longer than in similar patients receiving other TKI more than 38 months.
2. Despite the small number of groups and the small number of sudden deaths, they had a statistically significant QTc prolongation in 24-hour Holter ECG monitoring compared to those currently living or died from CML progression.
3. All CML patients treating with nilotinib are indicated to receive not only classical ECG, but also regular 24-hour Holter ECG monitoring with its greater sensitivity to detection of QTc prolongation.
Keyword(s): Chronic myeloid leukemia, Nilotinib
Abstract: PB1524
Type: Publication Only
Session title: Chronic myeloid leukemia - Clinical
Background
There are only few descriptions available in literature about the QTc prolongation and sudden cardiac death during treatment using BCR-ABL tyrosine kinase inhibitors.
Aims
Analysis of corrected interval QT (QTc) prolongation and sudden cardiac death of patients with chronic myeloid leukemia (CML) treated with BCR-ABL tyrosine kinase inhibitors (TKI).
Methods
The study was conducted on 114 patients who received nilotinibb, dasatinib or imatinib. All the patients underwent classical ECG monitoring and 24-hour Holter ECG monitoring with measuring of QTc duration. The trial excluded patients with severe heart diseases.
Results
Conducted comparative analysis shows statistically significant greater impact of nilotinib on the duration of QTc interval compared to other tyrosine kinase inhibitors. The maximum QTc was slightly longer than in patients treated with imatinib and dazatinib already at the early and middle stages (up to 36 months), but these differences are statistically insignificant. The main differences can be seen in patients taking nilotinib over 38 months, when these differences become statistically significant: median and interquartile range in patients on nilotinib therapy were 0.46 (0.44-0.47) s, n = 17 versus 0.43 (0.42-0.44) s in the group of patients taking dazatinib or imatinib (n=23), p=0.0004. After 7 years, we found out the fate of 110 examined patients. It turned out that 4 CML patients treated with ITK died suddenly. During analysis of the obtained data, it was found that the QTc duration in the ECG of the deceased did not differ from the survivors. At the same time, the QTc in 24-hour Holter ECG monitoring of 4 patients with sudden cardiac death was statistically significant longer than in the rest: 0.48 (0.48-0.505) s (n = 4) versus 0.45 (0.43-0.46) s (n = 110) (p=0.0003). Since all of the deceased were over the age of 52, the examination results of patients of this age were studied. A similar data was found in the group of patients older than 52 years: QTc duration of patients who died from sudden cardiac death - 0.48 (0.48-0.505) s, who are currently living or died from other reasons - 0.44 (0.43-0.46) s (n=56), p=0.001. All cases of sudden cardiac death occurred on nilotinib treatment (p=0.01), and the estimation of this indicator in the group of patients older than 52 years of age shows an identical trend with lower statistical significance (p=0.05).
Conclusion
1. We have shown that in patients with CML taking nilotinib, the QTc duration is statistically significant longer than in similar patients receiving other TKI more than 38 months.
2. Despite the small number of groups and the small number of sudden deaths, they had a statistically significant QTc prolongation in 24-hour Holter ECG monitoring compared to those currently living or died from CML progression.
3. All CML patients treating with nilotinib are indicated to receive not only classical ECG, but also regular 24-hour Holter ECG monitoring with its greater sensitivity to detection of QTc prolongation.
Keyword(s): Chronic myeloid leukemia, Nilotinib