BCL2 expression but not MYC and BCL2 coexpression predicts survival in elderly patients with diffuse large B-cell lymphoma independently of cell of origin in the phase 3 LNH03-6B trial.
BACKGROUND
Our aim was to evaluate whether the cell of origin (COO) as defined by the Hans algorithm and MYC/BCL2 coexpression, which are the two main biological risk factors in elderly patients treated with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisolone (R-CHOP), maintain their prognostic value in a large prospective clinical trial.


METHODS
We evaluated 285 paraffin-embedded samples from patients (60-80 years of age) enrolled in the Lymphoma Study Association trial LNH03-6B who were treated with R-CHOP. We correlated the COO defined by the transcriptome according to the Wright algorithm with that defined by the Hans algorithm in a subset of 62 tumors with available frozen tissue samples.


RESULTS
The non-germinal center B-cell-like phenotype according to the Hans algorithm and BCL2 expression (but not MYC and BCL2 coexpression) predicted worse progression-free survival [hazard ratio (HR)=1.78, P = 0.003 and HR = 1.79, P = 0.003, respectively] and overall survival (HR = 1.85, P = 0.005 and HR = 1.67, P = 0.02, respectively) independently of the International Prognostic Index. The correlation between the Hans algorithm and the Wright algorithm was 91%, with an almost perfect concordance according to a kappa test (0.81).


CONCLUSIONS
Our results suggest that immunohistochemically defined COO remains a useful tool for predicting prognosis in diffuse large B-cell lymphoma when performed under optimized standardized conditions and that BCL2 expression may help to identify elderly patients at risk for relapse and who could potentially respond to anti-BCL2 targeted agents. In this prospective phase III trial, the coexpression of MYC and BCL2 does not appear to predict worse survival.


BACKGROUND
NCT00144755.
Pathology, CHU Dijon, Dijon.
T
T
Petrella
Pathology, AP-HP, Groupe Hospitalier Henri-Mondor/Albert-Chenevier, Université Paris-Est Créteil, Créteil and IMRB, INSERM U955 Unité, Créteil.
C
C
Copie-Bergman
Pathology, AP-HP, Necker, Université Paris Descartes, Sorbonne Paris Cité, Paris.
J
J
Brière
Hematology, AP-HP, Necker Enfants-Malades, Paris.
R
R
Delarue
Hematology and UMR918, Centre Henri Becquerel, Université de Rouen, Rouen.
F
F
Jardin
Hematology and UMR918, Centre Henri Becquerel, Université de Rouen, Rouen.
P
P
Ruminy
Hemato-Oncology, AP-HP, Saint-Louis, Université Paris Diderot, Sorbonne Paris Cité and EA 7324, Paris Descartes, Sorbonne Paris Cité, Paris.
C
C
Thieblemont
Functional Genomic Platform, Cancer Research Institute, Lille.
M
M
Figeac
Pathology, AP-HP, Necker, Université Paris Descartes, Sorbonne Paris Cité, Paris.
D
D
Canioni
Hematology, CHU Nancy, Nancy.
P
P
Feugier
Pathology, AP-HP, Saint-Antoine, Paris.
B
B
Fabiani
Pathology, AP-HP, Groupe Hospitalier Henri-Mondor/Albert-Chenevier, Université Paris-Est Créteil, Créteil and IMRB, INSERM U955 Unité, Créteil.
K
K
Leroy
Pathology, CHU Bordeaux, Inserm U1053, Bordeaux, France.
M
M
Parrens
Hematology, Université Catholique de Louvain, CHU UCL Namur, Yvoir, Belgium.
M
M
André
Lymphoid Malignancies Unit, AP-HP, Groupe Hospitalier Henri-Mondor/Albert-Chenevier, Université Paris-Est Créteil, Créteil.
C
C
Haioun
Haematology, Hospices Civils de Lyon, Université Claude Bernard, Pierre Bénite.
G A
GA
Salles
Pathology, AP-HP, Groupe Hospitalier Henri-Mondor/Albert-Chenevier, Université Paris-Est Créteil, Créteil and IMRB, INSERM U955 Unité, Créteil.
P
P
Gaulard
Hematology and UMR918, Centre Henri Becquerel, Université de Rouen, Rouen.
H
H
Tilly
Biostatistics, AP-HP, Necker Enfants Malades, Université Paris Descartes, Sorbonne Paris Cité, Paris.
J P
JP
Jais
Pathology, AP-HP, Necker, Université Paris Descartes, Sorbonne Paris Cité, Paris.|EA7324, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
T J
TJ
Molina
D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D014408:Biomarkers, Tumor / Q000235:genetics; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D012307:Risk Factors; D000069283:Rituximab; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; C489427:MYC protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
BCL2; MYC; cell of origin; diffuse large B-cell lymphoma; immunohistochemistry; prognosis