Introduction: In large B-cell lymphoma (LBCL) MYC translocation and MYC/BCL2 or BCL6 double hit (DH) is associated with poor prognosis and there is an unmet need for novel treatment targets in this patient group. Treatment targeting the PD-L1/PD-1 pathway has been successfully introduced in Hodgkin lymphoma and solid cancers but are still poorly elucidated in LBCL. PD-L1 expression might predict response to treatment targeting the PD-L1/PD-1 pathway. We therefore investigated the relationship between PD-L1 protein and mRNA expression levels and MYC and DH translocation in LBCL.

Material and Methods: MYC, BCL2 and BCL6 translocations were detected by fluorescent in situ hybridization in tissue samples from 130 patients randomly selected from two cohorts of patients with LBCL: 49 patients with MYC translocation of whom 36 patients had DH and 81 without MYC translocation. PD-L1 protein expression was detected by immunohistochemistry (IHC) in tissue samples from 77 patients and PD-L1 mRNA expression by next-generation RNA sequencing (NGS) in another 77 patients. 24 patients overlapped, i.e. were analysed with both IHC and NGS. Nonparametric tests were performed to evaluate intergroup differences.

Results: PD-L1 protein expression level was lower in patients with MYC translocation (n=42, median=3,3%, IQR 0,0-10,8) or DH (n=31, median=3,3%, IQR 0,0-10,0) compared to patients with no MYC translocation (n=35, median=16,7%, IQR 3,3-30,0) or DH (n=46, 13,3%, IQR 2,5-30,0), P=0.004 and P<0,001 respectively (Fig.1). PD-L1 mRNA expression was also significantly lower in patients with MYC translocation or DH, P=0,001 and P=0,006 respectively. Higher PD-L1 protein and mRNA expression levels were associated with non-GC-type compared to GC-type DLBCL, P= 0,004 and P=0,002 respectively.

Conclusions: We report a highly significant association between low PD-L1 expression and MYC and DH translocation in patients with LBCL. Our findings may indicate that patients with MYC or DH translocation may benefit less from treatment with PD-L1/PD-1-inhibitors compared to patients without these translocations. This should be evaluated in larger, prospective, consecutive trials.

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Disclosures

No relevant conflicts of interest to declare.

Topics:
b-lymphocytes, lymphoma, programmed cell death 1 ligand 1, translocation (genetics), rna, messenger, bcl-2 protein, massively-parallel genome sequencing, tissue specimen, cancer, diffuse large b-cell lymphoma

Author notes

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Asterisk with author names denotes non-ASH members.

© 2018 by The American Society of Hematology
2018
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