Are there clinically relevant prognostic factors in diffuse large B-cell lymphoma beyond International Prognostic Index?

Abstract

Background. Diffuse large B-cell lymphoma (DLBCL) has variable prognosis, with only 50 to 60% of patients cured by standard first line treatment. Identifying patients unlikely to benefit from standard first line therapy is therefore crucial. Schmitz’s study identified four molecular subtypes of DLBCL with differing prognoses: MCD, BN2, N1, and EZB, with BN2 and EZB showing more favorable outcomes.

Materials and methods. We classified 131 DLBCL patients using Hans algorithm into GCB (germinal center B-cell-like) and ABC (activated B-cell-like) subtypes, and with next-generation sequencing (NGS) into ABC, GCB, unclassified, and into Schmitz’s novel genetic subtypes. A mutational analysis of just 7 genes (MYD88^L265P, CD79B, EZH2, NOTCH1, NOTCH2, BCL2, and BCL6) was used for genetic classification. Various statistical models were applied to assess survival differences between subtypes.

Results. 35.9% of patients were successfully classified into new genetic subtypes, with acceptable consistency between immunohistochemical (IHC) and NGS method for cell of origin (COO) determination. However, the new genetic subtype classification by NGS did not correlate with overall survival, nor did the COO classifications by IHC or NGS. Including these classifications also did not improve the predictive value of models compared to the basic model based on the International Prognostic Index (IPI) only.

Conclusions. The Archer FusionPlex Lymphoma assay showed a somewhat lower detection rate of novel genetic subtypes compared to reports based on exome sequencing, yet identified novel genetic subtypes in over one-third of patients. However, an in-depth statistical analysis did not confirm its predictive value for DLBCL prognosis, likely due to factors like patient selection and sample size limitations.