PD-L1 status in refractory lymphomas

Background

Targeted immune therapy based on PD-1/PD-L1 suppression has revolutionized the treatment of various solid tumors. A remarkable improvement has also observed in the treatment of patients with refractory/relapsing classical Hodgkin lymphoma (cHL). We investigated PD-L1 status in a variety of treatment resistant lymphomas.

Methods

FFPE samples from 79 patients with refractory/resistant lymphomas of B- and T-cell lineages were explored for the expression of PD-L1 (clones: SP142 and SP263, Ventana) using immunohistochemistry. Twelve PD-L1+ cases by IHC were further tested for PD-L1/JAK2/PD-L2 co-amplification using FISH/CISH assays or analyzed for gene copy number variations (CNV) using massively parallel sequencing (Illumina, NGS).

Results

PD-L1 positivity (≥5% positive cancer cells) was present in 32/78 (41%) and 33/72 cases (46%) using SP142 and SP263 antibodies, respectively. Concordance between the two clones was high with only three (4%) discrepant cases (Spearman's correlation coefficient 0.965). The strongest (3 + / ≥ 50% cells) and consistent (10/11 cases) expression was observed in Reed-Sternberg cells of cHL and primary mediastinal B-cell (3/3) lymphoma. Diffuse large B-cell lymphomas (DLBCL) were frequently positive (13/26) irrespective of subtype. Follicular (1/8), peripheral T-cell (2/9) and mantle cell (1/8) lymphomas were rarely positive, while small lymphocytic lymphoma/CLL and marginal zone lymphomas were consistently negative. Co-amplification/CNVs of PD-L1/JAK2/PD-L2 were observed in 3 cases of DLBCL and cHL, respectively.

Conclusions

Over-expression of PD-L1 with an excellent concordance between SP142 and SP263 antibodies was observed in cHL, DLBCL, primary mediastinal B-cell, follicular and peripheral T-cell lymphomas. Clinical relevance and therapeutic implications of co-amplification of PD-L1/JAK2/PD-L2 (50% of tested IHC+ cases) should be further investigated, as other mechanisms are also underlying the overexpression of PD-L1 in lymphomas.

Clinical trial identification

Legal entity responsible for the study

N/A

Funding

Caris Life Sciences

Disclosure

J. Kimbrough: Employee of Caris Life Sciences, Phoenix, Arizona, USA D. Arguello, Y. Veloso, S. Reddy, Z. Gatalica: Employee of Caris Life Sciences, Phoenix, AZ, USA All other authors have declared no conflicts of interest.