PD‐L1 expression is low in large B‐cell lymphoma with MYC or double‐hit translocation
- 25 August 2019
- journal article
- research article
- Published by Wiley in Hematological Oncology
- Vol. 37 (4), 375-382
- https://doi.org/10.1002/hon.2664
Abstract
In large B-cell lymphoma (LBCL), MYC translocation and MYC/BCL2 or MYC/BCL6 double hit (DH) are associated with poor prognosis, and there is an unmet need for novel treatment targets in this patient group. Treatments targeting the PD-L1/PD-1 pathway 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. We detected MYC, BCL2, and BCL6 translocation 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 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. Twenty-four patients overlapped, ie, were analysed with both IHC and NGS. Nonparametric tests were performed to evaluate intergroup differences. PD-L1 protein expression level was significantly lower in patients with MYC (n = 42, median = 3.3%, interquartile range [IQR] 0.0-10.8) or DH translocations (n = 31, median = 3.3%, IQR 0.0-10.0) compared with patients with no MYC (n = 35, median = 16.7%, IQR 3.3-30.0) or no DH translocations (n = 46, 13.3%, IQR 2.5-30.0), P = .004 and P <= .001, respectively. PD-L1 mRNA expression was also significantly lower in patients with MYC or DH translocations, P = .001 and P = .006, respectively. Higher PD-L1 protein and mRNA expression levels were associated with non-germinal centre (GC) type compared with germinal centre B-cell (GCB)-type diffuse LBCL (DLBCL), P = .004 and P = .002, respectively. In conclusion, we report an 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 with patients without these translocations. This should be evaluated in larger, prospective, consecutive trials.Keywords
This publication has 18 references indexed in Scilit:
- PD‐1/PD‐L1 inhibitors in haematological malignancies: update 2017Immunology, 2017
- PD-L1 Expression as a Predictive Biomarker in Advanced Non-Small-Cell Lung Cancer: Updated Survival DataImmunotherapy, 2017
- The expression and clinical relevance of PD-1, PD-L1, and TP63 in patients with diffuse large B-cell lymphomaMedicine, 2017
- PD-1–PD-L1 immune-checkpoint blockade in B-cell lymphomasNature Reviews Clinical Oncology, 2016
- Nivolumab in Patients With Relapsed or Refractory Hematologic Malignancy: Preliminary Results of a Phase Ib StudyJournal of Clinical Oncology, 2016
- Expression of programmed cell death ligand 1 is associated with poor overall survival in patients with diffuse large B-cell lymphomaBlood, 2015
- MYC translocation partner gene determines survival of patients with large B‐cell lymphoma with MYC‐ or double‐hit MYC/BCL2 translocationsEuropean Journal of Haematology, 2013
- PD-L1 Expression Is Characteristic of a Subset of Aggressive B-cell Lymphomas and Virus-Associated MalignanciesClinical Cancer Research, 2013
- Double‐hit BCL2/MYC translocations in a consecutive cohort of patients with large B‐cell lymphoma – a single centre's experienceEuropean Journal of Haematology, 2012
- Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarrayBlood, 2004