A BIOCLINICAL PROGNOSTIC MODEL INCORPORATING MYC AND BCL2 PREDICTS OUTCOME TO SALVAGE THERAPY IN RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA: AN NCIC CTG LY12 CORRELATIVE SCIENCE STUDY.
(Abstract release date: 05/19/16)
EHA Library. Stewart D. 06/11/16; 135235; S479
Douglas A Stewart
Contributions
Contributions
Abstract
Abstract: S479
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:30 - 16:45
Location: Hall A1
Background
Less than 50% of patients (pts) with relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL) achieve long-term event-free (EFS) and overall (OS) survival with salvage therapy. Better predictors of outcome are needed for these pts.
Aims
To determine clinical and molecular predictors of EFS and OS for rrDLBCL pts treated with rituximab (R) and either gemcitabine, dexamethasone, cisplatin (R-GDP) or dexamethasone, cytarabine, cisplatin (R-DHAP) followed by autologous stem-cell transplantation (ASCT) on the Canadian Cancer Trials Group LY12 study.
Methods
In total, 91 pts had DLBCL and sufficient histologic material to create tissue microarrays and undergo immunohistochemical (IHC) testing for CD10, BCL6, MUM1, FOXP1, LMO2, BCL2, CMYC, P53, pySTAT3 expression. In addition, 97 formalin-fixed, paraffin-embedded tissue samples underwent gene expression profiling (GEP) using NanoString to evaluate Cell of Origin (COO) by the Lymph2Cx assay, as well as BCL2, MYC, P53, STAT3, PDL1 and PD1 expression. Survival analysis was performed using the Kaplan-Meier method and Cox regression.
Results
COO was not associated with EFS or OS, according to the Hans IHC algorithm or the Lymph2Cx assay. Expression of py-STAT3 (>50%), P53 (>30%), MYC (>40%), and BCL2 (>70%) by IHC was found in 7.6%, 19.8%, 36.3%, 63.7%, of patient samples respectively. Expression of MYC was associated with lower 3-year (y) EFS rates (10% versus (vs) 42%, p=0.007) and OS rates (29% vs 56%, p=0.002) compared to MYC- patients. Similarly, 3y EFS rates were 25% vs 41% (p=0.029) and OS rates were 37% vs 63% (p=0.020) for BCL2+ vs BCL2- cases, respectively. The 22 pts with IHC-based dual expressing (DE) lymphomas (MYC+/BCL+) had significantly worse 3y EFS (0% vs 40%, p=0.0009) and OS rates (20% vs 54%, p=0.0004) relative to the 69 pts with without DE phenotype. In addition, p53+ vs p53- lymphomas had 3y EFS rates of 11% vs 36% (p=0.034). STAT3 was not associated with EFS or OS. Similar to IHC, both MYC and BCL2 expression using NanoString GEP (>1.5 x mean) were significantly associated with inferior OS and EFS, and no patient who expressed both markers achieved 2y EFS or OS. For the 82 lymphomas with samples for both IHC and GEP, a concordance rate of 79% was seen for MYC and 57% for BCL2. Expression of PD1 (p=0.03) but not PDL1 (p=0.41) by GEP was associated with inferior EFS. In multivariate analyses, 4 factors were adversely associated with EFS and OS: primary refractory DLBCL, elevated serum LDH at relapse, MYC expression and BCL2 expression (assessed by either IHC or GEP). Using these 4 factors, a bio-clinical score predicted EFS and OS from initiation of salvage chemotherapy. Using IHC to assess MYC and BCL2, 3y EFS was 55% for 34 pts with 0-1 factor vs 16% for 53 patients with 2-4 factors (p<0.0001). Similarly, using GEP to assess MYC and BCL2, the 3y EFS was 46% for 58 pts with 0-1 factor vs 5% for 39 pts with 2-4 factors (p<0.0001, see figure). The same 4 factor model predicted EFS for the 54 pts who received ASCT: 3y EFS 68% for 0-1 factor vs 34% for 2-4 factors (p=0.013) assessing MYC and BCL2 by IHC, or 53% for 0-1 factor vs 18% for 2-4 factors (p=0.008) when assessing MYC/BCL2 by GEP.
Conclusion
In conclusion, MYC and BCL2 expression, determined by IHC or Nanostring GEP, are independent poor prognostic factors for rrDLBCL, and dual expression predicts dismal prognosis. Combining MYC and BCL2 expression, primary refractory disease and elevated LDH results in a robust bio-clinical model strongly associated with EFS and OS for rrDLBCL, including chemosensitive patients who proceed to ASCT.
Session topic: Diffuse large B-cell lymphoma
Keyword(s): Autologous hematopoietic stem cell transplantation, Diffuse large B cell lymphoma, Molecular markers, Prognostic groups
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:30 - 16:45
Location: Hall A1
Background
Less than 50% of patients (pts) with relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL) achieve long-term event-free (EFS) and overall (OS) survival with salvage therapy. Better predictors of outcome are needed for these pts.
Aims
To determine clinical and molecular predictors of EFS and OS for rrDLBCL pts treated with rituximab (R) and either gemcitabine, dexamethasone, cisplatin (R-GDP) or dexamethasone, cytarabine, cisplatin (R-DHAP) followed by autologous stem-cell transplantation (ASCT) on the Canadian Cancer Trials Group LY12 study.
Methods
In total, 91 pts had DLBCL and sufficient histologic material to create tissue microarrays and undergo immunohistochemical (IHC) testing for CD10, BCL6, MUM1, FOXP1, LMO2, BCL2, CMYC, P53, pySTAT3 expression. In addition, 97 formalin-fixed, paraffin-embedded tissue samples underwent gene expression profiling (GEP) using NanoString to evaluate Cell of Origin (COO) by the Lymph2Cx assay, as well as BCL2, MYC, P53, STAT3, PDL1 and PD1 expression. Survival analysis was performed using the Kaplan-Meier method and Cox regression.
Results
COO was not associated with EFS or OS, according to the Hans IHC algorithm or the Lymph2Cx assay. Expression of py-STAT3 (>50%), P53 (>30%), MYC (>40%), and BCL2 (>70%) by IHC was found in 7.6%, 19.8%, 36.3%, 63.7%, of patient samples respectively. Expression of MYC was associated with lower 3-year (y) EFS rates (10% versus (vs) 42%, p=0.007) and OS rates (29% vs 56%, p=0.002) compared to MYC- patients. Similarly, 3y EFS rates were 25% vs 41% (p=0.029) and OS rates were 37% vs 63% (p=0.020) for BCL2+ vs BCL2- cases, respectively. The 22 pts with IHC-based dual expressing (DE) lymphomas (MYC+/BCL+) had significantly worse 3y EFS (0% vs 40%, p=0.0009) and OS rates (20% vs 54%, p=0.0004) relative to the 69 pts with without DE phenotype. In addition, p53+ vs p53- lymphomas had 3y EFS rates of 11% vs 36% (p=0.034). STAT3 was not associated with EFS or OS. Similar to IHC, both MYC and BCL2 expression using NanoString GEP (>1.5 x mean) were significantly associated with inferior OS and EFS, and no patient who expressed both markers achieved 2y EFS or OS. For the 82 lymphomas with samples for both IHC and GEP, a concordance rate of 79% was seen for MYC and 57% for BCL2. Expression of PD1 (p=0.03) but not PDL1 (p=0.41) by GEP was associated with inferior EFS. In multivariate analyses, 4 factors were adversely associated with EFS and OS: primary refractory DLBCL, elevated serum LDH at relapse, MYC expression and BCL2 expression (assessed by either IHC or GEP). Using these 4 factors, a bio-clinical score predicted EFS and OS from initiation of salvage chemotherapy. Using IHC to assess MYC and BCL2, 3y EFS was 55% for 34 pts with 0-1 factor vs 16% for 53 patients with 2-4 factors (p<0.0001). Similarly, using GEP to assess MYC and BCL2, the 3y EFS was 46% for 58 pts with 0-1 factor vs 5% for 39 pts with 2-4 factors (p<0.0001, see figure). The same 4 factor model predicted EFS for the 54 pts who received ASCT: 3y EFS 68% for 0-1 factor vs 34% for 2-4 factors (p=0.013) assessing MYC and BCL2 by IHC, or 53% for 0-1 factor vs 18% for 2-4 factors (p=0.008) when assessing MYC/BCL2 by GEP.
Conclusion
In conclusion, MYC and BCL2 expression, determined by IHC or Nanostring GEP, are independent poor prognostic factors for rrDLBCL, and dual expression predicts dismal prognosis. Combining MYC and BCL2 expression, primary refractory disease and elevated LDH results in a robust bio-clinical model strongly associated with EFS and OS for rrDLBCL, including chemosensitive patients who proceed to ASCT.
Session topic: Diffuse large B-cell lymphoma
Keyword(s): Autologous hematopoietic stem cell transplantation, Diffuse large B cell lymphoma, Molecular markers, Prognostic groups
Abstract: S479
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:30 - 16:45
Location: Hall A1
Background
Less than 50% of patients (pts) with relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL) achieve long-term event-free (EFS) and overall (OS) survival with salvage therapy. Better predictors of outcome are needed for these pts.
Aims
To determine clinical and molecular predictors of EFS and OS for rrDLBCL pts treated with rituximab (R) and either gemcitabine, dexamethasone, cisplatin (R-GDP) or dexamethasone, cytarabine, cisplatin (R-DHAP) followed by autologous stem-cell transplantation (ASCT) on the Canadian Cancer Trials Group LY12 study.
Methods
In total, 91 pts had DLBCL and sufficient histologic material to create tissue microarrays and undergo immunohistochemical (IHC) testing for CD10, BCL6, MUM1, FOXP1, LMO2, BCL2, CMYC, P53, pySTAT3 expression. In addition, 97 formalin-fixed, paraffin-embedded tissue samples underwent gene expression profiling (GEP) using NanoString to evaluate Cell of Origin (COO) by the Lymph2Cx assay, as well as BCL2, MYC, P53, STAT3, PDL1 and PD1 expression. Survival analysis was performed using the Kaplan-Meier method and Cox regression.
Results
COO was not associated with EFS or OS, according to the Hans IHC algorithm or the Lymph2Cx assay. Expression of py-STAT3 (>50%), P53 (>30%), MYC (>40%), and BCL2 (>70%) by IHC was found in 7.6%, 19.8%, 36.3%, 63.7%, of patient samples respectively. Expression of MYC was associated with lower 3-year (y) EFS rates (10% versus (vs) 42%, p=0.007) and OS rates (29% vs 56%, p=0.002) compared to MYC- patients. Similarly, 3y EFS rates were 25% vs 41% (p=0.029) and OS rates were 37% vs 63% (p=0.020) for BCL2+ vs BCL2- cases, respectively. The 22 pts with IHC-based dual expressing (DE) lymphomas (MYC+/BCL+) had significantly worse 3y EFS (0% vs 40%, p=0.0009) and OS rates (20% vs 54%, p=0.0004) relative to the 69 pts with without DE phenotype. In addition, p53+ vs p53- lymphomas had 3y EFS rates of 11% vs 36% (p=0.034). STAT3 was not associated with EFS or OS. Similar to IHC, both MYC and BCL2 expression using NanoString GEP (>1.5 x mean) were significantly associated with inferior OS and EFS, and no patient who expressed both markers achieved 2y EFS or OS. For the 82 lymphomas with samples for both IHC and GEP, a concordance rate of 79% was seen for MYC and 57% for BCL2. Expression of PD1 (p=0.03) but not PDL1 (p=0.41) by GEP was associated with inferior EFS. In multivariate analyses, 4 factors were adversely associated with EFS and OS: primary refractory DLBCL, elevated serum LDH at relapse, MYC expression and BCL2 expression (assessed by either IHC or GEP). Using these 4 factors, a bio-clinical score predicted EFS and OS from initiation of salvage chemotherapy. Using IHC to assess MYC and BCL2, 3y EFS was 55% for 34 pts with 0-1 factor vs 16% for 53 patients with 2-4 factors (p<0.0001). Similarly, using GEP to assess MYC and BCL2, the 3y EFS was 46% for 58 pts with 0-1 factor vs 5% for 39 pts with 2-4 factors (p<0.0001, see figure). The same 4 factor model predicted EFS for the 54 pts who received ASCT: 3y EFS 68% for 0-1 factor vs 34% for 2-4 factors (p=0.013) assessing MYC and BCL2 by IHC, or 53% for 0-1 factor vs 18% for 2-4 factors (p=0.008) when assessing MYC/BCL2 by GEP.
Conclusion
In conclusion, MYC and BCL2 expression, determined by IHC or Nanostring GEP, are independent poor prognostic factors for rrDLBCL, and dual expression predicts dismal prognosis. Combining MYC and BCL2 expression, primary refractory disease and elevated LDH results in a robust bio-clinical model strongly associated with EFS and OS for rrDLBCL, including chemosensitive patients who proceed to ASCT.
Session topic: Diffuse large B-cell lymphoma
Keyword(s): Autologous hematopoietic stem cell transplantation, Diffuse large B cell lymphoma, Molecular markers, Prognostic groups
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:30 - 16:45
Location: Hall A1
Background
Less than 50% of patients (pts) with relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL) achieve long-term event-free (EFS) and overall (OS) survival with salvage therapy. Better predictors of outcome are needed for these pts.
Aims
To determine clinical and molecular predictors of EFS and OS for rrDLBCL pts treated with rituximab (R) and either gemcitabine, dexamethasone, cisplatin (R-GDP) or dexamethasone, cytarabine, cisplatin (R-DHAP) followed by autologous stem-cell transplantation (ASCT) on the Canadian Cancer Trials Group LY12 study.
Methods
In total, 91 pts had DLBCL and sufficient histologic material to create tissue microarrays and undergo immunohistochemical (IHC) testing for CD10, BCL6, MUM1, FOXP1, LMO2, BCL2, CMYC, P53, pySTAT3 expression. In addition, 97 formalin-fixed, paraffin-embedded tissue samples underwent gene expression profiling (GEP) using NanoString to evaluate Cell of Origin (COO) by the Lymph2Cx assay, as well as BCL2, MYC, P53, STAT3, PDL1 and PD1 expression. Survival analysis was performed using the Kaplan-Meier method and Cox regression.
Results
COO was not associated with EFS or OS, according to the Hans IHC algorithm or the Lymph2Cx assay. Expression of py-STAT3 (>50%), P53 (>30%), MYC (>40%), and BCL2 (>70%) by IHC was found in 7.6%, 19.8%, 36.3%, 63.7%, of patient samples respectively. Expression of MYC was associated with lower 3-year (y) EFS rates (10% versus (vs) 42%, p=0.007) and OS rates (29% vs 56%, p=0.002) compared to MYC- patients. Similarly, 3y EFS rates were 25% vs 41% (p=0.029) and OS rates were 37% vs 63% (p=0.020) for BCL2+ vs BCL2- cases, respectively. The 22 pts with IHC-based dual expressing (DE) lymphomas (MYC+/BCL+) had significantly worse 3y EFS (0% vs 40%, p=0.0009) and OS rates (20% vs 54%, p=0.0004) relative to the 69 pts with without DE phenotype. In addition, p53+ vs p53- lymphomas had 3y EFS rates of 11% vs 36% (p=0.034). STAT3 was not associated with EFS or OS. Similar to IHC, both MYC and BCL2 expression using NanoString GEP (>1.5 x mean) were significantly associated with inferior OS and EFS, and no patient who expressed both markers achieved 2y EFS or OS. For the 82 lymphomas with samples for both IHC and GEP, a concordance rate of 79% was seen for MYC and 57% for BCL2. Expression of PD1 (p=0.03) but not PDL1 (p=0.41) by GEP was associated with inferior EFS. In multivariate analyses, 4 factors were adversely associated with EFS and OS: primary refractory DLBCL, elevated serum LDH at relapse, MYC expression and BCL2 expression (assessed by either IHC or GEP). Using these 4 factors, a bio-clinical score predicted EFS and OS from initiation of salvage chemotherapy. Using IHC to assess MYC and BCL2, 3y EFS was 55% for 34 pts with 0-1 factor vs 16% for 53 patients with 2-4 factors (p<0.0001). Similarly, using GEP to assess MYC and BCL2, the 3y EFS was 46% for 58 pts with 0-1 factor vs 5% for 39 pts with 2-4 factors (p<0.0001, see figure). The same 4 factor model predicted EFS for the 54 pts who received ASCT: 3y EFS 68% for 0-1 factor vs 34% for 2-4 factors (p=0.013) assessing MYC and BCL2 by IHC, or 53% for 0-1 factor vs 18% for 2-4 factors (p=0.008) when assessing MYC/BCL2 by GEP.
Conclusion
In conclusion, MYC and BCL2 expression, determined by IHC or Nanostring GEP, are independent poor prognostic factors for rrDLBCL, and dual expression predicts dismal prognosis. Combining MYC and BCL2 expression, primary refractory disease and elevated LDH results in a robust bio-clinical model strongly associated with EFS and OS for rrDLBCL, including chemosensitive patients who proceed to ASCT.
Session topic: Diffuse large B-cell lymphoma
Keyword(s): Autologous hematopoietic stem cell transplantation, Diffuse large B cell lymphoma, Molecular markers, Prognostic groups
{{ help_message }}
{{filter}}