THE PROGNOSTIC SIGNIFICANCE OF DEL1P IN MULTIPLE MYELOMA PATIENTS.
(Abstract release date: 05/19/16)
EHA Library. Nedeva A. 06/09/16; 132878; E1329
Dr. Antoniya Nedeva
Contributions
Contributions
Abstract
Abstract: E1329
Type: Eposter Presentation
Background
The genomic characteristics of the malignant clone are an important aspect of multiple myeloma pathogenesis. It is well known that the disease is associated with certain cytogenetic abnormalities, some of which confer poor prognosis. The detection of these abnormalities with fluorescence in situ hybridization (FISH) can identify a group of patients with high risk who should be treated differently compared to those with standard risk.
Aims
Identification of genetic markers as independent prognostic factors for survival in multiple myeloma patients and assessment of their significance in the era of novel agents.
Methods
92 newly-diagnosed multiple myeloma patients with performed FISH and/or conventional cytogenetics were evaluated. FISH analysis was performed in 76 patients, using specific probes for the most frequent high-risk genetic markers, including t(4;14), del17p, del13, amp1q and del1p. Prognostic factors for progression-free survival (PFS) and overall survival (OS) were identified by means of the Cox proportional hazard model for covariate analysis. As possible prognostic factors the following parameters were included in the regression model: age, β2-microglobulin levels, hemoglobin levels, platelet counts, creatinine, calcium, percentage of bone-marrow infiltration, extramedullary disease, plasmablast morphology and presence or absence of the above mentioned genomic aberrations. Median survival times were calculated and compared according to the presence or absence of a particular high-risk aberration and the type of induction therapy (bortezomib-based or conventional). Kaplan-Meier curves were plotted and compared using the log-rank test. Statistical analyses were performed with the program SPSS v21.
Results
The prevalence of high-risk genomic aberrations in our patient cohort was as follows: del13 in 39 (42.4%) patients; amp1q - in 22 (23.9%); del1p and del17p each in 15 (16.3%), and t(4;14) in 8 (8.7%) patients. In our analyses only high β2-microglobulin levels (р=0,035) and del1p (р=0,000) were independent prognostic factors for PFS, while high β2-microglobulin (р=0.002), thrombocytopenia (р=0.037) and del17p (р=0.006) were independent predictors of poor OS. Among the high-risk genetic abnormalities del1p and del17p had the greatest negative influence on patients‘ outcome, regardless of the induction therapy performed (conventional or bortezomib-based). Patients with del1p and 17p had a significantly shorter median survival, compared with patients without these aberrations, even after induction with a novel agent: 16 months vs. 79 months for del1p (p=0.014) and 12 months vs. 79 months for del17p (p=0.001).
Conclusion
Del17p is a well-known adverse prognostic factor in multiple myeloma which is included in the risk stratification models. Presence of this aberration predicts short survival and such patients are candidates for clinical trials. Only few data however are present on the prognostic significance of del1p in the era of novel agents. According to our results patients with del1p should be considered high-risk, similarly to patients with del17p, and may be candidates for more aggressive induction therapy.
Session topic: E-poster
Keyword(s): Bortezomib, Cytogenetic abnormalities, Multiple myeloma, Survival
Type: Eposter Presentation
Background
The genomic characteristics of the malignant clone are an important aspect of multiple myeloma pathogenesis. It is well known that the disease is associated with certain cytogenetic abnormalities, some of which confer poor prognosis. The detection of these abnormalities with fluorescence in situ hybridization (FISH) can identify a group of patients with high risk who should be treated differently compared to those with standard risk.
Aims
Identification of genetic markers as independent prognostic factors for survival in multiple myeloma patients and assessment of their significance in the era of novel agents.
Methods
92 newly-diagnosed multiple myeloma patients with performed FISH and/or conventional cytogenetics were evaluated. FISH analysis was performed in 76 patients, using specific probes for the most frequent high-risk genetic markers, including t(4;14), del17p, del13, amp1q and del1p. Prognostic factors for progression-free survival (PFS) and overall survival (OS) were identified by means of the Cox proportional hazard model for covariate analysis. As possible prognostic factors the following parameters were included in the regression model: age, β2-microglobulin levels, hemoglobin levels, platelet counts, creatinine, calcium, percentage of bone-marrow infiltration, extramedullary disease, plasmablast morphology and presence or absence of the above mentioned genomic aberrations. Median survival times were calculated and compared according to the presence or absence of a particular high-risk aberration and the type of induction therapy (bortezomib-based or conventional). Kaplan-Meier curves were plotted and compared using the log-rank test. Statistical analyses were performed with the program SPSS v21.
Results
The prevalence of high-risk genomic aberrations in our patient cohort was as follows: del13 in 39 (42.4%) patients; amp1q - in 22 (23.9%); del1p and del17p each in 15 (16.3%), and t(4;14) in 8 (8.7%) patients. In our analyses only high β2-microglobulin levels (р=0,035) and del1p (р=0,000) were independent prognostic factors for PFS, while high β2-microglobulin (р=0.002), thrombocytopenia (р=0.037) and del17p (р=0.006) were independent predictors of poor OS. Among the high-risk genetic abnormalities del1p and del17p had the greatest negative influence on patients‘ outcome, regardless of the induction therapy performed (conventional or bortezomib-based). Patients with del1p and 17p had a significantly shorter median survival, compared with patients without these aberrations, even after induction with a novel agent: 16 months vs. 79 months for del1p (p=0.014) and 12 months vs. 79 months for del17p (p=0.001).
Conclusion
Del17p is a well-known adverse prognostic factor in multiple myeloma which is included in the risk stratification models. Presence of this aberration predicts short survival and such patients are candidates for clinical trials. Only few data however are present on the prognostic significance of del1p in the era of novel agents. According to our results patients with del1p should be considered high-risk, similarly to patients with del17p, and may be candidates for more aggressive induction therapy.
Session topic: E-poster
Keyword(s): Bortezomib, Cytogenetic abnormalities, Multiple myeloma, Survival
Abstract: E1329
Type: Eposter Presentation
Background
The genomic characteristics of the malignant clone are an important aspect of multiple myeloma pathogenesis. It is well known that the disease is associated with certain cytogenetic abnormalities, some of which confer poor prognosis. The detection of these abnormalities with fluorescence in situ hybridization (FISH) can identify a group of patients with high risk who should be treated differently compared to those with standard risk.
Aims
Identification of genetic markers as independent prognostic factors for survival in multiple myeloma patients and assessment of their significance in the era of novel agents.
Methods
92 newly-diagnosed multiple myeloma patients with performed FISH and/or conventional cytogenetics were evaluated. FISH analysis was performed in 76 patients, using specific probes for the most frequent high-risk genetic markers, including t(4;14), del17p, del13, amp1q and del1p. Prognostic factors for progression-free survival (PFS) and overall survival (OS) were identified by means of the Cox proportional hazard model for covariate analysis. As possible prognostic factors the following parameters were included in the regression model: age, β2-microglobulin levels, hemoglobin levels, platelet counts, creatinine, calcium, percentage of bone-marrow infiltration, extramedullary disease, plasmablast morphology and presence or absence of the above mentioned genomic aberrations. Median survival times were calculated and compared according to the presence or absence of a particular high-risk aberration and the type of induction therapy (bortezomib-based or conventional). Kaplan-Meier curves were plotted and compared using the log-rank test. Statistical analyses were performed with the program SPSS v21.
Results
The prevalence of high-risk genomic aberrations in our patient cohort was as follows: del13 in 39 (42.4%) patients; amp1q - in 22 (23.9%); del1p and del17p each in 15 (16.3%), and t(4;14) in 8 (8.7%) patients. In our analyses only high β2-microglobulin levels (р=0,035) and del1p (р=0,000) were independent prognostic factors for PFS, while high β2-microglobulin (р=0.002), thrombocytopenia (р=0.037) and del17p (р=0.006) were independent predictors of poor OS. Among the high-risk genetic abnormalities del1p and del17p had the greatest negative influence on patients‘ outcome, regardless of the induction therapy performed (conventional or bortezomib-based). Patients with del1p and 17p had a significantly shorter median survival, compared with patients without these aberrations, even after induction with a novel agent: 16 months vs. 79 months for del1p (p=0.014) and 12 months vs. 79 months for del17p (p=0.001).
Conclusion
Del17p is a well-known adverse prognostic factor in multiple myeloma which is included in the risk stratification models. Presence of this aberration predicts short survival and such patients are candidates for clinical trials. Only few data however are present on the prognostic significance of del1p in the era of novel agents. According to our results patients with del1p should be considered high-risk, similarly to patients with del17p, and may be candidates for more aggressive induction therapy.
Session topic: E-poster
Keyword(s): Bortezomib, Cytogenetic abnormalities, Multiple myeloma, Survival
Type: Eposter Presentation
Background
The genomic characteristics of the malignant clone are an important aspect of multiple myeloma pathogenesis. It is well known that the disease is associated with certain cytogenetic abnormalities, some of which confer poor prognosis. The detection of these abnormalities with fluorescence in situ hybridization (FISH) can identify a group of patients with high risk who should be treated differently compared to those with standard risk.
Aims
Identification of genetic markers as independent prognostic factors for survival in multiple myeloma patients and assessment of their significance in the era of novel agents.
Methods
92 newly-diagnosed multiple myeloma patients with performed FISH and/or conventional cytogenetics were evaluated. FISH analysis was performed in 76 patients, using specific probes for the most frequent high-risk genetic markers, including t(4;14), del17p, del13, amp1q and del1p. Prognostic factors for progression-free survival (PFS) and overall survival (OS) were identified by means of the Cox proportional hazard model for covariate analysis. As possible prognostic factors the following parameters were included in the regression model: age, β2-microglobulin levels, hemoglobin levels, platelet counts, creatinine, calcium, percentage of bone-marrow infiltration, extramedullary disease, plasmablast morphology and presence or absence of the above mentioned genomic aberrations. Median survival times were calculated and compared according to the presence or absence of a particular high-risk aberration and the type of induction therapy (bortezomib-based or conventional). Kaplan-Meier curves were plotted and compared using the log-rank test. Statistical analyses were performed with the program SPSS v21.
Results
The prevalence of high-risk genomic aberrations in our patient cohort was as follows: del13 in 39 (42.4%) patients; amp1q - in 22 (23.9%); del1p and del17p each in 15 (16.3%), and t(4;14) in 8 (8.7%) patients. In our analyses only high β2-microglobulin levels (р=0,035) and del1p (р=0,000) were independent prognostic factors for PFS, while high β2-microglobulin (р=0.002), thrombocytopenia (р=0.037) and del17p (р=0.006) were independent predictors of poor OS. Among the high-risk genetic abnormalities del1p and del17p had the greatest negative influence on patients‘ outcome, regardless of the induction therapy performed (conventional or bortezomib-based). Patients with del1p and 17p had a significantly shorter median survival, compared with patients without these aberrations, even after induction with a novel agent: 16 months vs. 79 months for del1p (p=0.014) and 12 months vs. 79 months for del17p (p=0.001).
Conclusion
Del17p is a well-known adverse prognostic factor in multiple myeloma which is included in the risk stratification models. Presence of this aberration predicts short survival and such patients are candidates for clinical trials. Only few data however are present on the prognostic significance of del1p in the era of novel agents. According to our results patients with del1p should be considered high-risk, similarly to patients with del17p, and may be candidates for more aggressive induction therapy.
Session topic: E-poster
Keyword(s): Bortezomib, Cytogenetic abnormalities, Multiple myeloma, Survival
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