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TREATMENT OF C-MYC/BCL2 DOUBLE EXPRESSER DLBCL WITH R-CHOP CHEMOIMMUNOTHERAPY: AN AUSTRALIAN SINGLE CENTRE EXPERIENCE
Author(s): ,
Teng Fong Ng
Affiliations:
Clinical Haematology,University Hospital Geelong,Geelong,Australia;Haematology,Fiona Stanley Hospital,Perth,Australia
,
Andrea Whiteside
Affiliations:
Anatomical Pathology,St John of God Pathology,Geelong,Australia
,
Hannah Rose
Affiliations:
Clinical Haematology,University Hospital Geelong,Geelong,Australia
,
David Kipp
Affiliations:
Clinical Haematology,University Hospital Geelong,Geelong,Australia
,
Bassam Tawfik
Affiliations:
Anatomical Pathology,St John of God Pathology,Geelong,Australia
Philip Campbell
Affiliations:
Clinical Haematology,University Hospital Geelong,Geelong,Australia;School of Medicine,Deakin University,Geelong,Australia
(Abstract release date: 05/19/16) EHA Library. Ng T. 06/09/16; 134624; PB1724
Dr. Teng Fong Ng
Dr. Teng Fong Ng
Contributions
Abstract
Abstract: PB1724

Type: Publication Only

Background
Co-expression of c-myc and BCL2 in Diffuse Large B-cell Lymphoma (DLBCL), (increasingly known as ‘double expresser’ DLBCL), is associated with inferior outcome with standard-of-care R-CHOP immunochemotherapy. 

Aims
To retrospectively identify patients with ‘double expresser’ immunophenotype within our patient cohort of DLBCL, and to analyze their outcomes following treatment. 

Methods
Chart review of patients with DLBCL treated with RCHOP chemoimmunotherapy between 2007 and 2014 at our institution. We retrospectively performed immunohistochemical staining for c-myc and BCL2 on pre-treatment tumor tissue blocks to identify patients with ‘double expresser’ immunophenotype. Other prognostic factors including the revised international prognostic index (R-IPI) score, initial bulky disease (>7.5cm) and cell of origin were also recorded and analyzed.Progression-free survival (PFS) were analyzed using Kaplan–Meier curves and statistically tested with the Gehan-Breslow-Wilcoxon test. 2-tailed chi-square test was used to compare incidence of various prognostic factors in subgroup analysis.

Results
89 patients were included in the study. Patients with high risk R-IPI score, bulky disease, and elevated serum lactate dehydrogenase level (LDH) showed reduced progression-free survival (p=0.03, p=0.04, p=0.002 respectively). In particular, LDH above 2 times of upper limit of normal (ULN) was associated with a 56% reduction in PFS. There was no significant difference in PFS between ‘germinal center’ and ‘non-germinal center’ cell of origin subtypes of DLBCL.34 patients were found to have ‘double expresser’ immunophenotype.  They showed a higher rate of disease progression (32% vs 16%, p=0.03), than the remaining DLBCL patients, with progression occurring predominantly within 24 months of treatment. The ‘double expresser’ subgroup also had a higher incidence of bulky disease (50% vs 13%, p=0.01), and LDH above 2xULN (35% vs 11%, p=0.005), at presentation. All patients with normal LDH levels and non-bulky disease (n=7) remained in remission at a median follow-up of 32 months.

Conclusion
We present a small single center series of ‘double expresser’ DLBCL. Patients with the double expresser phenotype had a higher incidence of bulky disease and markedly elevated LDH level, which was associated with higher risk of disease progression. Knowing this, it may be reasonable to adopt a more intensive treatment approach for these patients. Interestingly, having a normal LDH level at diagnosis and absence of bulky disease (known good prognostic factors) retained their protective influence even in patients with ‘double expresser’ phenotype.



Session topic: E-poster

Keyword(s): BCL2, C-myc, Diffuse large B cell lymphoma, Immunohistochemistry
Abstract: PB1724

Type: Publication Only

Background
Co-expression of c-myc and BCL2 in Diffuse Large B-cell Lymphoma (DLBCL), (increasingly known as ‘double expresser’ DLBCL), is associated with inferior outcome with standard-of-care R-CHOP immunochemotherapy. 

Aims
To retrospectively identify patients with ‘double expresser’ immunophenotype within our patient cohort of DLBCL, and to analyze their outcomes following treatment. 

Methods
Chart review of patients with DLBCL treated with RCHOP chemoimmunotherapy between 2007 and 2014 at our institution. We retrospectively performed immunohistochemical staining for c-myc and BCL2 on pre-treatment tumor tissue blocks to identify patients with ‘double expresser’ immunophenotype. Other prognostic factors including the revised international prognostic index (R-IPI) score, initial bulky disease (>7.5cm) and cell of origin were also recorded and analyzed.Progression-free survival (PFS) were analyzed using Kaplan–Meier curves and statistically tested with the Gehan-Breslow-Wilcoxon test. 2-tailed chi-square test was used to compare incidence of various prognostic factors in subgroup analysis.

Results
89 patients were included in the study. Patients with high risk R-IPI score, bulky disease, and elevated serum lactate dehydrogenase level (LDH) showed reduced progression-free survival (p=0.03, p=0.04, p=0.002 respectively). In particular, LDH above 2 times of upper limit of normal (ULN) was associated with a 56% reduction in PFS. There was no significant difference in PFS between ‘germinal center’ and ‘non-germinal center’ cell of origin subtypes of DLBCL.34 patients were found to have ‘double expresser’ immunophenotype.  They showed a higher rate of disease progression (32% vs 16%, p=0.03), than the remaining DLBCL patients, with progression occurring predominantly within 24 months of treatment. The ‘double expresser’ subgroup also had a higher incidence of bulky disease (50% vs 13%, p=0.01), and LDH above 2xULN (35% vs 11%, p=0.005), at presentation. All patients with normal LDH levels and non-bulky disease (n=7) remained in remission at a median follow-up of 32 months.

Conclusion
We present a small single center series of ‘double expresser’ DLBCL. Patients with the double expresser phenotype had a higher incidence of bulky disease and markedly elevated LDH level, which was associated with higher risk of disease progression. Knowing this, it may be reasonable to adopt a more intensive treatment approach for these patients. Interestingly, having a normal LDH level at diagnosis and absence of bulky disease (known good prognostic factors) retained their protective influence even in patients with ‘double expresser’ phenotype.



Session topic: E-poster

Keyword(s): BCL2, C-myc, Diffuse large B cell lymphoma, Immunohistochemistry

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