BORTEZOMIB-BASED TREATMENT MAY OVERCOME THE ADVERSE EFFECT OF FOPNL GENOMIC VARIANT ON THE PROGNOSIS OF MULTIPLE MYELOMA
(Abstract release date: 05/19/16)
EHA Library. Kiss K. 06/09/16; 132827; E1278
Ms. Katalin Piroska Kiss
Contributions
Contributions
Abstract
Abstract: E1278
Type: Eposter Presentation
Background
In a recent genome-wide association study (GWAS), the FOPNL (fibroblast growth factor receptor 1 oncogen partner N terminal like gene) single nucleotide polymorphism rs72773978 was identified as a novel adverse prognostic factor in multiple myeloma (MM).
Aims
The aim of our study was to investigate the associations of FOPNL polymorphism with clinical characteristics (sex, age, ISS, cytogenetic abnormalities) as well as treatment outcome (progression free survival, [PFS] and overall survival, [OS]) in a cohort of Hungarian MM patients.
Methods
Data of 373 MM patients (188 male/185 female; mean age: 60.5±11.2 year) diagnosed from 2005 to 2013 were retrospectively analysed. As a first line treatment, older regimens (containing no proteasome inhibitor) were administered in 132 cases, while PI based therapy was applied in 241 cases. The minimal follow up was 24 month. LightCycler melting analysis was applied to identify rs72773978 polymorphism.
Results
In the whole cohort applying a dominant model, the distribution of rs72773978 polymorphism was as follows: AA:328/373 (87.9%) vs. AT&TT: 45/373, (12.1%). We found no significant difference in sex, age, ISS stage or citogenetics stratified subgroups. In our cohort FOPNL polymorphism showed difference in the prognostic effect depending on the treatment applied. In line with the previous GWAS study, carriership of the minor allele was significantly associated with adverse PFS among patients treated with non-PI based therapy (p=0.042). PFS at 24 months was 43.5±4.5% for AA patients (n=124) compared to 12.5±11.7% for AT&TT patients (n=8). Suprisingly in the PI treatment group, PFS at 24 months was 51.7±3.5% for AA (n=204) compared to 62.2±8% for AT&TT (n=37) patients (p=0.082). As significant interaction between FOPNL and PI treatment was observed (p=0.003), we performed multivariate analyses (Cox regression considering considering sex, age and ISS as covariates) in both treatment groups separately. The difference did not remain significant in either groups (non PI group: p=0.22; HR: 1.78, 95% CI: 0.7-4.5, PI group: p=0.094; HR: 0.7, 95% CI: 0.47-1.06). Similar comparisons for OS revealed a similar effect of FOPNL variant in both treatment groups. In the non-PI treated group adverse prognosis was observed in minor allele carriers: OS at 72 months for AA patients was 49±4.6% compared to AT&TT with 18.8±15.8% (p=0.022). In the PI-based group, OS at 72 months for AA patients was 40.9±4.5% compared to AT&TT 67.3±8.5% (p=0.048). The test for interaction between FOPNL and treatment was significant (p<0.001). Separate multivariate analyses revealed the independent adverse effect of rs72773978 on survival in the non PI group (p=0.029; HR: 2.9, 95% CI: 1.1-7.6); but not in PI treatment group: p=0.155; HR: 0.63, 95% CI: 0.34-1.19).
Conclusion
In the present study, we confirmed the adverse prognostic effect of FOPNL rs72773978 polymorphism in case of non-PI based treatment regimens. On contrary this adverse effect was overcome by the application of newer, proteasome inhibitor containing treatment protocols.
Session topic: E-poster
Keyword(s): Bortezomib, Multiple myeloma, SNP
Type: Eposter Presentation
Background
In a recent genome-wide association study (GWAS), the FOPNL (fibroblast growth factor receptor 1 oncogen partner N terminal like gene) single nucleotide polymorphism rs72773978 was identified as a novel adverse prognostic factor in multiple myeloma (MM).
Aims
The aim of our study was to investigate the associations of FOPNL polymorphism with clinical characteristics (sex, age, ISS, cytogenetic abnormalities) as well as treatment outcome (progression free survival, [PFS] and overall survival, [OS]) in a cohort of Hungarian MM patients.
Methods
Data of 373 MM patients (188 male/185 female; mean age: 60.5±11.2 year) diagnosed from 2005 to 2013 were retrospectively analysed. As a first line treatment, older regimens (containing no proteasome inhibitor) were administered in 132 cases, while PI based therapy was applied in 241 cases. The minimal follow up was 24 month. LightCycler melting analysis was applied to identify rs72773978 polymorphism.
Results
In the whole cohort applying a dominant model, the distribution of rs72773978 polymorphism was as follows: AA:328/373 (87.9%) vs. AT&TT: 45/373, (12.1%). We found no significant difference in sex, age, ISS stage or citogenetics stratified subgroups. In our cohort FOPNL polymorphism showed difference in the prognostic effect depending on the treatment applied. In line with the previous GWAS study, carriership of the minor allele was significantly associated with adverse PFS among patients treated with non-PI based therapy (p=0.042). PFS at 24 months was 43.5±4.5% for AA patients (n=124) compared to 12.5±11.7% for AT&TT patients (n=8). Suprisingly in the PI treatment group, PFS at 24 months was 51.7±3.5% for AA (n=204) compared to 62.2±8% for AT&TT (n=37) patients (p=0.082). As significant interaction between FOPNL and PI treatment was observed (p=0.003), we performed multivariate analyses (Cox regression considering considering sex, age and ISS as covariates) in both treatment groups separately. The difference did not remain significant in either groups (non PI group: p=0.22; HR: 1.78, 95% CI: 0.7-4.5, PI group: p=0.094; HR: 0.7, 95% CI: 0.47-1.06). Similar comparisons for OS revealed a similar effect of FOPNL variant in both treatment groups. In the non-PI treated group adverse prognosis was observed in minor allele carriers: OS at 72 months for AA patients was 49±4.6% compared to AT&TT with 18.8±15.8% (p=0.022). In the PI-based group, OS at 72 months for AA patients was 40.9±4.5% compared to AT&TT 67.3±8.5% (p=0.048). The test for interaction between FOPNL and treatment was significant (p<0.001). Separate multivariate analyses revealed the independent adverse effect of rs72773978 on survival in the non PI group (p=0.029; HR: 2.9, 95% CI: 1.1-7.6); but not in PI treatment group: p=0.155; HR: 0.63, 95% CI: 0.34-1.19).
Conclusion
In the present study, we confirmed the adverse prognostic effect of FOPNL rs72773978 polymorphism in case of non-PI based treatment regimens. On contrary this adverse effect was overcome by the application of newer, proteasome inhibitor containing treatment protocols.
Session topic: E-poster
Keyword(s): Bortezomib, Multiple myeloma, SNP
Abstract: E1278
Type: Eposter Presentation
Background
In a recent genome-wide association study (GWAS), the FOPNL (fibroblast growth factor receptor 1 oncogen partner N terminal like gene) single nucleotide polymorphism rs72773978 was identified as a novel adverse prognostic factor in multiple myeloma (MM).
Aims
The aim of our study was to investigate the associations of FOPNL polymorphism with clinical characteristics (sex, age, ISS, cytogenetic abnormalities) as well as treatment outcome (progression free survival, [PFS] and overall survival, [OS]) in a cohort of Hungarian MM patients.
Methods
Data of 373 MM patients (188 male/185 female; mean age: 60.5±11.2 year) diagnosed from 2005 to 2013 were retrospectively analysed. As a first line treatment, older regimens (containing no proteasome inhibitor) were administered in 132 cases, while PI based therapy was applied in 241 cases. The minimal follow up was 24 month. LightCycler melting analysis was applied to identify rs72773978 polymorphism.
Results
In the whole cohort applying a dominant model, the distribution of rs72773978 polymorphism was as follows: AA:328/373 (87.9%) vs. AT&TT: 45/373, (12.1%). We found no significant difference in sex, age, ISS stage or citogenetics stratified subgroups. In our cohort FOPNL polymorphism showed difference in the prognostic effect depending on the treatment applied. In line with the previous GWAS study, carriership of the minor allele was significantly associated with adverse PFS among patients treated with non-PI based therapy (p=0.042). PFS at 24 months was 43.5±4.5% for AA patients (n=124) compared to 12.5±11.7% for AT&TT patients (n=8). Suprisingly in the PI treatment group, PFS at 24 months was 51.7±3.5% for AA (n=204) compared to 62.2±8% for AT&TT (n=37) patients (p=0.082). As significant interaction between FOPNL and PI treatment was observed (p=0.003), we performed multivariate analyses (Cox regression considering considering sex, age and ISS as covariates) in both treatment groups separately. The difference did not remain significant in either groups (non PI group: p=0.22; HR: 1.78, 95% CI: 0.7-4.5, PI group: p=0.094; HR: 0.7, 95% CI: 0.47-1.06). Similar comparisons for OS revealed a similar effect of FOPNL variant in both treatment groups. In the non-PI treated group adverse prognosis was observed in minor allele carriers: OS at 72 months for AA patients was 49±4.6% compared to AT&TT with 18.8±15.8% (p=0.022). In the PI-based group, OS at 72 months for AA patients was 40.9±4.5% compared to AT&TT 67.3±8.5% (p=0.048). The test for interaction between FOPNL and treatment was significant (p<0.001). Separate multivariate analyses revealed the independent adverse effect of rs72773978 on survival in the non PI group (p=0.029; HR: 2.9, 95% CI: 1.1-7.6); but not in PI treatment group: p=0.155; HR: 0.63, 95% CI: 0.34-1.19).
Conclusion
In the present study, we confirmed the adverse prognostic effect of FOPNL rs72773978 polymorphism in case of non-PI based treatment regimens. On contrary this adverse effect was overcome by the application of newer, proteasome inhibitor containing treatment protocols.
Session topic: E-poster
Keyword(s): Bortezomib, Multiple myeloma, SNP
Type: Eposter Presentation
Background
In a recent genome-wide association study (GWAS), the FOPNL (fibroblast growth factor receptor 1 oncogen partner N terminal like gene) single nucleotide polymorphism rs72773978 was identified as a novel adverse prognostic factor in multiple myeloma (MM).
Aims
The aim of our study was to investigate the associations of FOPNL polymorphism with clinical characteristics (sex, age, ISS, cytogenetic abnormalities) as well as treatment outcome (progression free survival, [PFS] and overall survival, [OS]) in a cohort of Hungarian MM patients.
Methods
Data of 373 MM patients (188 male/185 female; mean age: 60.5±11.2 year) diagnosed from 2005 to 2013 were retrospectively analysed. As a first line treatment, older regimens (containing no proteasome inhibitor) were administered in 132 cases, while PI based therapy was applied in 241 cases. The minimal follow up was 24 month. LightCycler melting analysis was applied to identify rs72773978 polymorphism.
Results
In the whole cohort applying a dominant model, the distribution of rs72773978 polymorphism was as follows: AA:328/373 (87.9%) vs. AT&TT: 45/373, (12.1%). We found no significant difference in sex, age, ISS stage or citogenetics stratified subgroups. In our cohort FOPNL polymorphism showed difference in the prognostic effect depending on the treatment applied. In line with the previous GWAS study, carriership of the minor allele was significantly associated with adverse PFS among patients treated with non-PI based therapy (p=0.042). PFS at 24 months was 43.5±4.5% for AA patients (n=124) compared to 12.5±11.7% for AT&TT patients (n=8). Suprisingly in the PI treatment group, PFS at 24 months was 51.7±3.5% for AA (n=204) compared to 62.2±8% for AT&TT (n=37) patients (p=0.082). As significant interaction between FOPNL and PI treatment was observed (p=0.003), we performed multivariate analyses (Cox regression considering considering sex, age and ISS as covariates) in both treatment groups separately. The difference did not remain significant in either groups (non PI group: p=0.22; HR: 1.78, 95% CI: 0.7-4.5, PI group: p=0.094; HR: 0.7, 95% CI: 0.47-1.06). Similar comparisons for OS revealed a similar effect of FOPNL variant in both treatment groups. In the non-PI treated group adverse prognosis was observed in minor allele carriers: OS at 72 months for AA patients was 49±4.6% compared to AT&TT with 18.8±15.8% (p=0.022). In the PI-based group, OS at 72 months for AA patients was 40.9±4.5% compared to AT&TT 67.3±8.5% (p=0.048). The test for interaction between FOPNL and treatment was significant (p<0.001). Separate multivariate analyses revealed the independent adverse effect of rs72773978 on survival in the non PI group (p=0.029; HR: 2.9, 95% CI: 1.1-7.6); but not in PI treatment group: p=0.155; HR: 0.63, 95% CI: 0.34-1.19).
Conclusion
In the present study, we confirmed the adverse prognostic effect of FOPNL rs72773978 polymorphism in case of non-PI based treatment regimens. On contrary this adverse effect was overcome by the application of newer, proteasome inhibitor containing treatment protocols.
Session topic: E-poster
Keyword(s): Bortezomib, Multiple myeloma, SNP
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