DIFFUSE LARGE B‐CELL LYMPHOMA SURVIVAL PROGNOSTICATION, A COMPARATIVE ANALYSIS OF CELL OF ORIGIN VS. MYC/BCL2 EXPRESSION

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Introduction: Multiple conflicting prognostic markers have been proposed for R-CHOP treated diffuse large B-cell lymphoma (DLBCL) cases. Aggressive behaviour has been shown to be associated with ABC-like phenotype, Double Hit (DH) or Double Expression (DE) phenotype, CD5 expression and other molecular or immunohistochemical markers. Methods: Here we have analyzed the survival probability in a series of chemoimmunotherapy-treated 100 DLBCL cases comparing COO vs. MYC/BCL2 gene expression vs. the expression of other prognostic markers such as CD30, PDL1, CD5, p53 and Ki67, using a NanoString custom assay that includes COO and other 7 genes. Data have been also correlated with immunohistochemical and other cytogenetic studies. Univariable and multivariable Cox proportional hazard regression models were used to evaluate the proposed prognostic factors. For Kaplan Meier analysis the continuous series were divided taken into account the median value and quartiles of the series. Results: Double Expression (DE) (MYC/BCL2) was found in 26 cases and related with a shorter time to progression (TTP) (HR: 1.95, P<0.05). COO analysis identified 53 cases as GC-type; 27 as ABC-type and 19 unclassified. ABC-phenotype was associated with shorter overall survival (OS) (HR:2.5; p<0.05). Association between ABC and DE identified 11 cases with double expression and ABC-phenotype, with a HR: 2.82, n<0.05. Clinical variables integrated into the IPI were significantly associated with both TTP and OS. All the three parameters were basically independent prognostic markers. When associated, multivariate analysis allowed to integrate IPI, DE and COO into a single model, identifying an integrated risk score for each sample that stratifies the series into four groups from risk quartiles (0.50, 0.74 and 1.56) with very strong differences in TTP and DSS. The relapse probabilities at 36 months for the risk groups created were 0.90, 0.67, 0.43 and 0.35 from down risk to high risk, while the OS probabilities at 36 months were 0.96, 0.71, 0.64 and 0.52. Conclusions: DE (MYC/BCL2), COO and IPI are independent prognostic markers in CHOP-R treated DLBCL cases. An integrated risk score identified quartiles with significant differences in OS, TTP and DSS, and could eventually be used for selecting risk-stratified therapeutic strategies. Keywords: “double-hit” lymphomas; activated B-cell-like (ABC); diffuse large B-cell lymphoma (DLBCL).

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