Contributions
Abstract: PB1522
Type: Publication Only
Session title: Chronic myeloid leukemia - Clinical
Background
Targeted inhibition of the mutant tyrosine kinase BCR-ABL-1 (Philadelphia chromosome fusion protein) is one of the brightest advances in medical science. Thanks to this fundamental discovery, patients with chronic myeloid leukemia (CML) today have a life expectancy comparable to that of people without CML. However, additional mutations in the kinase domain of the BCR-ABL-1 gene result in resistance to the effect of tyrosine kinase inhibitors (TKIs). Different TKIs cover a different spectrum of mutations, and T315I is one of the most difficult to manage.
Aims
To study the frequency of T315I mutation in patients with CML, BCR-ABL + ; to analyze their clinical characteristics, disease evolution and median survival, and to compare with those of CML patients without established T315I mutation.
Methods
We studied 75 patients with CML, BCR-ABL1 + with suboptimal therapeutic response or loss of therapeutic respones. The detection and quantification of the T315I mutation was performed by digital droplet PCR (dd PCR) . Molecular studies for detection and quantification of BCR - ABL 1 fusion transcripts were performed by RT-PCR and presented on the international scale, according to ELN criteria. In patients with established T315I mutation (CML, T315I +) a comparative analysis was performed by sex and age, disease phase, risk group, treatment, type and duration of molecular response and median survival compared to patients with CML without T315i mutation (CML T315i-). Statistical data were processed with descriptive analysis, correlation analysis and Independent Sample T-test for comparison of mean values, at a level of significance p <0.05. Survival analysis was performed by the Kaplan-Meier method with a log-rank test.
Results
The T315I mutation was detected in 11 (14.7%) of CML patients. The m / f ratio in the T315I (+) group was 2/3, mean age 49.27 +/- 13.5 years, with no statistical difference from the whole cohort and patients without the T315I mutation. No statistically significant difference was found in the baseline characteristics of the disease between the two groups - phase, risk group (according to Sokal and Hasford) and choice of first-line therapy. A significantly higher proportion of CML T315I + patients did not achieve a molecular response >3.5 log throughout the follow-up period, compared to patients with CML T315I- : 8 (72.7%) vs 22(34.4%), p = 0.023. The lowest mean BCR-ABL -1 expression levels reached were significantly higher in the CML T315I + group compared to the CML T315I - group: 12.1 +/- 6.0 versus 3.77 + / 1.28 (p = 0.009). In patients with CML T315I +, the mean number of treatment lines was 3.2 compared to 1.1 in the CML T315I- group. The median survival (MS) of CML T315I + patients was significantly shorter than the MS of patients without the T315I- mutation: 73 months vs 175 months (p <0.0001).
Conclusion
Our data confirm the data from the accumulated world experience on the frequency of T315I mutation, as well as the unfavorable evolution, resistance to TKI treatment and short survival in patients with CML, T315I +. ddPCR is a highly sensitive and informative method for early detection of genetic mutations, even at low levels of expression. Timely detection of the T315I mutation, immediately after failure of first-line TKI therapy in patients with CML, gives the chance to choose effective treatment, improve their prognosis and long-term survival
Keyword(s): Chronic myeloid leukemia, Mutation analysis
Abstract: PB1522
Type: Publication Only
Session title: Chronic myeloid leukemia - Clinical
Background
Targeted inhibition of the mutant tyrosine kinase BCR-ABL-1 (Philadelphia chromosome fusion protein) is one of the brightest advances in medical science. Thanks to this fundamental discovery, patients with chronic myeloid leukemia (CML) today have a life expectancy comparable to that of people without CML. However, additional mutations in the kinase domain of the BCR-ABL-1 gene result in resistance to the effect of tyrosine kinase inhibitors (TKIs). Different TKIs cover a different spectrum of mutations, and T315I is one of the most difficult to manage.
Aims
To study the frequency of T315I mutation in patients with CML, BCR-ABL + ; to analyze their clinical characteristics, disease evolution and median survival, and to compare with those of CML patients without established T315I mutation.
Methods
We studied 75 patients with CML, BCR-ABL1 + with suboptimal therapeutic response or loss of therapeutic respones. The detection and quantification of the T315I mutation was performed by digital droplet PCR (dd PCR) . Molecular studies for detection and quantification of BCR - ABL 1 fusion transcripts were performed by RT-PCR and presented on the international scale, according to ELN criteria. In patients with established T315I mutation (CML, T315I +) a comparative analysis was performed by sex and age, disease phase, risk group, treatment, type and duration of molecular response and median survival compared to patients with CML without T315i mutation (CML T315i-). Statistical data were processed with descriptive analysis, correlation analysis and Independent Sample T-test for comparison of mean values, at a level of significance p <0.05. Survival analysis was performed by the Kaplan-Meier method with a log-rank test.
Results
The T315I mutation was detected in 11 (14.7%) of CML patients. The m / f ratio in the T315I (+) group was 2/3, mean age 49.27 +/- 13.5 years, with no statistical difference from the whole cohort and patients without the T315I mutation. No statistically significant difference was found in the baseline characteristics of the disease between the two groups - phase, risk group (according to Sokal and Hasford) and choice of first-line therapy. A significantly higher proportion of CML T315I + patients did not achieve a molecular response >3.5 log throughout the follow-up period, compared to patients with CML T315I- : 8 (72.7%) vs 22(34.4%), p = 0.023. The lowest mean BCR-ABL -1 expression levels reached were significantly higher in the CML T315I + group compared to the CML T315I - group: 12.1 +/- 6.0 versus 3.77 + / 1.28 (p = 0.009). In patients with CML T315I +, the mean number of treatment lines was 3.2 compared to 1.1 in the CML T315I- group. The median survival (MS) of CML T315I + patients was significantly shorter than the MS of patients without the T315I- mutation: 73 months vs 175 months (p <0.0001).
Conclusion
Our data confirm the data from the accumulated world experience on the frequency of T315I mutation, as well as the unfavorable evolution, resistance to TKI treatment and short survival in patients with CML, T315I +. ddPCR is a highly sensitive and informative method for early detection of genetic mutations, even at low levels of expression. Timely detection of the T315I mutation, immediately after failure of first-line TKI therapy in patients with CML, gives the chance to choose effective treatment, improve their prognosis and long-term survival
Keyword(s): Chronic myeloid leukemia, Mutation analysis