Value of PD-L1 Protein Expression in the Combined Prognostic Model of Diffuse Large B-Cell Lymphoma

Abstract

Aim. To study the value of PD-L1 protein expression in the combined model of diffuse large B-cell lymphoma (DLBCL) after administration of R-CHOP induction immunochemo-therapy. Materials & Methods. A retrospective analysis was based on the data of 85 DLBCL patients. The median age was 59 years (Q-Q<sub>3</sub>: 29-83). Each patient received at least 2-6 courses of R-CHOP immunochemotherapy. The median follow-up period was 17 months. The optimal cut-off threshold for assessing the proportion of tumor cells expressing PD-L1 protein was determined by the CART (Classification and Regression Tree) method. Results. Patients were divided into three groups depending on IPI (International Prognostic Index) risk and immunohis-tochemical subtype (Hans algorithm) using CART. In group 1 with immunohistochemical GCB subtype and any IPI risk, except for the high one, low PD-L1 expression measured in terms of the DLBCL expressing tumor cell count, was identified in 21 (84 %) patients, 4 (16 %) patients showed overexpression. In case of low PD-L1 expression the 2-year progression-free survival (PFS) was 76 % (median not reached). In 4 patients with protein overexpression, the life duration after DLBCL diagnosed was 4, 16, 2, and 6 months, respectively. In group 2 with immunohistochemical non-GCB subtype and any IPI risk, except for the high one, 27 (67.5 %) patients showed low, and 13 (32.5 %) patients showed high PD-L1 expression. The analysis of the 2-year PFS resulted in no significant differences in groups with different relative counts of PD-L1 expressing tumor cells, i.e., 46 % and 49 %, respectively (p = 0.803). In case of low (< 24.5 % tumor cells) PD-L1 expression, the 2-year overall survival (OS) was better than in patients with overexpression (> 24.5 % tumor cells), i.e., 87 % vs. 52 %, respectively (p = 0.049). In group 3 with IPI high risk irrespective of immunohistochemical subtype, the proportion of PD-L1 expressing cells was higher than cut-off threshold (> 24.5 %) in 9 (45 %) patients, low protein expression was identified in 11 (55 %) patients. Deaths were reported in all patients of group 3 showing PD-L1 overexpression. In case of low protein expression the proportion of patients alive was 46 % (p = 0.002). None of the patients with high PD-L1 expression lived longer than 2 years. In those with low PD-L1 expression the 2-year OS was 66 % (p = 0.008). Conclusion. Overexpression of PD-L1 by DLBCL tumor cells together with high IPI progression risk and non-GCB tumor subtype is associated with the worst OS and PFS. It can probably be accounted for by insufficient efficacy of R-CHOP induction immunochemotherapy in patients with high IPI risk. With this presumption, the PD-L1 expressing tumor cell count can be regarded as an important additional criterion for stratification of DLBCL patients into risk groups. Adding this new parameter to already established ones would probably contribute to differentiated approach to the choice of chemotherapy strategy at the onset of this aggressive lymphoma.