DOUBLE PROTEIN LYMPHOMA PATIENTS OF THE NON-GCB SUBTYPE HAVE AN INFERIOR PROGNOSIS WHEN TREATED WITH CHEMOIMMUNOTHERAPY
(Abstract release date: 05/19/16)
EHA Library. Troppan K. 06/09/16; 132514; E965
Dr. Katharina Troppan
Contributions
Contributions
Abstract
Abstract: E965
Type: Eposter Presentation
Background
Diffuse large B-cell lymphoma (DLBCL) can be stratified by cell of origin (COO) derivation into the prognostically favorable germinal center B-cell (GCB)–like and unfavorable activated B-cell (ABC) or non-GCB-like subtype based on gene expression signatures or immunohistochemical determination. Double-hit lymphoma (DHL) were identified as a subgroup of aggressive lymphomas with both MYC and BCL2 gene rearrangements, characterised by a rapidly progressing clinical course and short survival. Recently, DLBCL patients with an immunohistochemical coexpression of MYC and BCL2 also demonstrated inferior prognosis suggesting that concurrent expression of MYC/BCL2, termed double-protein-expression lymphoma (DPL), rather than cell-of-origin classification, is a better predictor of prognosis in patients treated with R-CHOP.
Aims
We determined the frequency of DPL in a large single center cohort of DLBCL uniformely treated with R-CHOP and evaluated patients’ outcome in contrast to “standard” DLBCL not exhibiting concurrent expression of MYC/BCL2.
Methods
We evaluated retrospectively the appearance of DPL in 440 patients with DLBCL, consecutively diagnosed and treated between 2004 and 2014 at our institution. To determine the double-hit score, immunohistochemistry for c-MYC and BCL2 was performed on diagnostic samples. Furthermore, the Choi algorithm was used to subclassify samples by cell-of-origin. On the basis of immunohistochemical MYC and BCL2 expression, a double-hit score (DHS) was assigned to all patients with DLBCL. The DHS-2 group was defined by high expression of both MYC and BCL2 protein.
Results
A GCB subtype was found in 162 patients, whereas 223 samples were classified as non-GCB subtype. For 55 patients, no classification according to cell-of-origin could be performed. Of 440 DLBCL, 289 patients were evaluable, 58 of them showed a double-hit score of 0, 168 patients had a DHS of 1, and 63 a DHS of 2, respectively. Twenty-one of 76 patients with a DHS of 2 could be classified as GCB, whereas 42 patients exhibited a non-GCB subtype. Using Kaplan-Meier curves and log-rank tests, we could demonstrate a significant inferior outcome for DLBCL patients with the non-GCB subtype as compared to the GCB subtype (, p<0.001). Further, DPL patients had also a shorter overall survival (OS) (p=0.05). Combining the cell-of-origin classification with the DHS, we were able to further discriminate a subgroup of patients with an even worse clinical outcome to standard treatment (median OS 81 vs. 44 months, p<0.001) (Figure 1).
Conclusion
In this large single center cohort, we could demonstrate a significant negative effect on OS for DLBCL patients coexpressing MYC and BCL2. We could further define a particular subgroup of patients within the non-GCB cohort demonstrating double hit positivity (DHS of 2) that is associated with a particular short survival. These non-GCB-, DHS positive DLBCL patients are candidates for novel therapeutic strategies.
Session topic: E-poster
Keyword(s): Diffuse large B cell lymphoma, MYC
Type: Eposter Presentation
Background
Diffuse large B-cell lymphoma (DLBCL) can be stratified by cell of origin (COO) derivation into the prognostically favorable germinal center B-cell (GCB)–like and unfavorable activated B-cell (ABC) or non-GCB-like subtype based on gene expression signatures or immunohistochemical determination. Double-hit lymphoma (DHL) were identified as a subgroup of aggressive lymphomas with both MYC and BCL2 gene rearrangements, characterised by a rapidly progressing clinical course and short survival. Recently, DLBCL patients with an immunohistochemical coexpression of MYC and BCL2 also demonstrated inferior prognosis suggesting that concurrent expression of MYC/BCL2, termed double-protein-expression lymphoma (DPL), rather than cell-of-origin classification, is a better predictor of prognosis in patients treated with R-CHOP.
Aims
We determined the frequency of DPL in a large single center cohort of DLBCL uniformely treated with R-CHOP and evaluated patients’ outcome in contrast to “standard” DLBCL not exhibiting concurrent expression of MYC/BCL2.
Methods
We evaluated retrospectively the appearance of DPL in 440 patients with DLBCL, consecutively diagnosed and treated between 2004 and 2014 at our institution. To determine the double-hit score, immunohistochemistry for c-MYC and BCL2 was performed on diagnostic samples. Furthermore, the Choi algorithm was used to subclassify samples by cell-of-origin. On the basis of immunohistochemical MYC and BCL2 expression, a double-hit score (DHS) was assigned to all patients with DLBCL. The DHS-2 group was defined by high expression of both MYC and BCL2 protein.
Results
A GCB subtype was found in 162 patients, whereas 223 samples were classified as non-GCB subtype. For 55 patients, no classification according to cell-of-origin could be performed. Of 440 DLBCL, 289 patients were evaluable, 58 of them showed a double-hit score of 0, 168 patients had a DHS of 1, and 63 a DHS of 2, respectively. Twenty-one of 76 patients with a DHS of 2 could be classified as GCB, whereas 42 patients exhibited a non-GCB subtype. Using Kaplan-Meier curves and log-rank tests, we could demonstrate a significant inferior outcome for DLBCL patients with the non-GCB subtype as compared to the GCB subtype (, p<0.001). Further, DPL patients had also a shorter overall survival (OS) (p=0.05). Combining the cell-of-origin classification with the DHS, we were able to further discriminate a subgroup of patients with an even worse clinical outcome to standard treatment (median OS 81 vs. 44 months, p<0.001) (Figure 1).
Conclusion
In this large single center cohort, we could demonstrate a significant negative effect on OS for DLBCL patients coexpressing MYC and BCL2. We could further define a particular subgroup of patients within the non-GCB cohort demonstrating double hit positivity (DHS of 2) that is associated with a particular short survival. These non-GCB-, DHS positive DLBCL patients are candidates for novel therapeutic strategies.
Session topic: E-poster
Keyword(s): Diffuse large B cell lymphoma, MYC
Abstract: E965
Type: Eposter Presentation
Background
Diffuse large B-cell lymphoma (DLBCL) can be stratified by cell of origin (COO) derivation into the prognostically favorable germinal center B-cell (GCB)–like and unfavorable activated B-cell (ABC) or non-GCB-like subtype based on gene expression signatures or immunohistochemical determination. Double-hit lymphoma (DHL) were identified as a subgroup of aggressive lymphomas with both MYC and BCL2 gene rearrangements, characterised by a rapidly progressing clinical course and short survival. Recently, DLBCL patients with an immunohistochemical coexpression of MYC and BCL2 also demonstrated inferior prognosis suggesting that concurrent expression of MYC/BCL2, termed double-protein-expression lymphoma (DPL), rather than cell-of-origin classification, is a better predictor of prognosis in patients treated with R-CHOP.
Aims
We determined the frequency of DPL in a large single center cohort of DLBCL uniformely treated with R-CHOP and evaluated patients’ outcome in contrast to “standard” DLBCL not exhibiting concurrent expression of MYC/BCL2.
Methods
We evaluated retrospectively the appearance of DPL in 440 patients with DLBCL, consecutively diagnosed and treated between 2004 and 2014 at our institution. To determine the double-hit score, immunohistochemistry for c-MYC and BCL2 was performed on diagnostic samples. Furthermore, the Choi algorithm was used to subclassify samples by cell-of-origin. On the basis of immunohistochemical MYC and BCL2 expression, a double-hit score (DHS) was assigned to all patients with DLBCL. The DHS-2 group was defined by high expression of both MYC and BCL2 protein.
Results
A GCB subtype was found in 162 patients, whereas 223 samples were classified as non-GCB subtype. For 55 patients, no classification according to cell-of-origin could be performed. Of 440 DLBCL, 289 patients were evaluable, 58 of them showed a double-hit score of 0, 168 patients had a DHS of 1, and 63 a DHS of 2, respectively. Twenty-one of 76 patients with a DHS of 2 could be classified as GCB, whereas 42 patients exhibited a non-GCB subtype. Using Kaplan-Meier curves and log-rank tests, we could demonstrate a significant inferior outcome for DLBCL patients with the non-GCB subtype as compared to the GCB subtype (, p<0.001). Further, DPL patients had also a shorter overall survival (OS) (p=0.05). Combining the cell-of-origin classification with the DHS, we were able to further discriminate a subgroup of patients with an even worse clinical outcome to standard treatment (median OS 81 vs. 44 months, p<0.001) (Figure 1).
Conclusion
In this large single center cohort, we could demonstrate a significant negative effect on OS for DLBCL patients coexpressing MYC and BCL2. We could further define a particular subgroup of patients within the non-GCB cohort demonstrating double hit positivity (DHS of 2) that is associated with a particular short survival. These non-GCB-, DHS positive DLBCL patients are candidates for novel therapeutic strategies.
Session topic: E-poster
Keyword(s): Diffuse large B cell lymphoma, MYC
Type: Eposter Presentation
Background
Diffuse large B-cell lymphoma (DLBCL) can be stratified by cell of origin (COO) derivation into the prognostically favorable germinal center B-cell (GCB)–like and unfavorable activated B-cell (ABC) or non-GCB-like subtype based on gene expression signatures or immunohistochemical determination. Double-hit lymphoma (DHL) were identified as a subgroup of aggressive lymphomas with both MYC and BCL2 gene rearrangements, characterised by a rapidly progressing clinical course and short survival. Recently, DLBCL patients with an immunohistochemical coexpression of MYC and BCL2 also demonstrated inferior prognosis suggesting that concurrent expression of MYC/BCL2, termed double-protein-expression lymphoma (DPL), rather than cell-of-origin classification, is a better predictor of prognosis in patients treated with R-CHOP.
Aims
We determined the frequency of DPL in a large single center cohort of DLBCL uniformely treated with R-CHOP and evaluated patients’ outcome in contrast to “standard” DLBCL not exhibiting concurrent expression of MYC/BCL2.
Methods
We evaluated retrospectively the appearance of DPL in 440 patients with DLBCL, consecutively diagnosed and treated between 2004 and 2014 at our institution. To determine the double-hit score, immunohistochemistry for c-MYC and BCL2 was performed on diagnostic samples. Furthermore, the Choi algorithm was used to subclassify samples by cell-of-origin. On the basis of immunohistochemical MYC and BCL2 expression, a double-hit score (DHS) was assigned to all patients with DLBCL. The DHS-2 group was defined by high expression of both MYC and BCL2 protein.
Results
A GCB subtype was found in 162 patients, whereas 223 samples were classified as non-GCB subtype. For 55 patients, no classification according to cell-of-origin could be performed. Of 440 DLBCL, 289 patients were evaluable, 58 of them showed a double-hit score of 0, 168 patients had a DHS of 1, and 63 a DHS of 2, respectively. Twenty-one of 76 patients with a DHS of 2 could be classified as GCB, whereas 42 patients exhibited a non-GCB subtype. Using Kaplan-Meier curves and log-rank tests, we could demonstrate a significant inferior outcome for DLBCL patients with the non-GCB subtype as compared to the GCB subtype (, p<0.001). Further, DPL patients had also a shorter overall survival (OS) (p=0.05). Combining the cell-of-origin classification with the DHS, we were able to further discriminate a subgroup of patients with an even worse clinical outcome to standard treatment (median OS 81 vs. 44 months, p<0.001) (Figure 1).
Conclusion
In this large single center cohort, we could demonstrate a significant negative effect on OS for DLBCL patients coexpressing MYC and BCL2. We could further define a particular subgroup of patients within the non-GCB cohort demonstrating double hit positivity (DHS of 2) that is associated with a particular short survival. These non-GCB-, DHS positive DLBCL patients are candidates for novel therapeutic strategies.
Session topic: E-poster
Keyword(s): Diffuse large B cell lymphoma, MYC
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