Abstract 3724: PDL1 protein expression and tumor mutation burden in hematologic malignancies: correlation with Hodgkin and high grade lymphoma

2017 
Background: The success of anti PD–1 therapy in Hodgkin lymphoma has led to clinical trials in other types of lymphomas. However, there is limited data on PD–L1 expression in acute leukemias. In this study, we analyzed PD–L1 protein expression and tumor mutational burden in various hematologic malignancies including leukemias, lymphomas and myelomas. Methods: In the IHC cohort, formalin fixed paraffin embedded sections from 92 hematologic malignancies including acute myeloid and lymphoblastic leukemia (AML, ALL), Hodgkin lymphoma (HL), diffuse large B-cell lymphoma (DLBCL), low-grade non-Hodgkin lymphoma (LGNHL) and myeloma were immunostained using the FDA approved PD-L1 IHC 22C3 pharmDx assay [monoclonal mouse anti-PD–L1 antibody (DAKO clone 22C3)]. Any perceptible partial or complete membrane staining in all viable tumor cells was scored as follows: 50%-high level PD-L1 expression. In the second cohort of 2064 cases, comprehensive genomic profiling (CGP) was performed using a hybrid–capture, adaptor ligation assay to a mean depth of >672X. Tumor mutation burden (TMB) was calculated from a minimum of 1.11MB of sequenced DNA as previously described and reported as mutations/MB. High PD–L1 expression was noted in 100% of HL. DLBCL showed significantly higher PD–L1 positivity compared to LGNHL (p=0.01). No correlation for PD–L1 expression was noted between AML and ALL (p = 0.2). On CGP analysis of the second cohort, TMB was significantly higher in DLBCL as compared to LGNHL (p Conclusion: The high PD-L1 expression in both HL and DLBCL and high TMB in DLBCL may be linked to enhanced responsiveness to check point inhibitor therapy in these cancers. PD-L1 expression and TMB are relatively infrequent and at low levels in acute leukemias. Additionally, novel anti PD–1/PD–L1 therapeutic strategies are worthy of consideration for both advanced stage refractory/relapsed acute myeloid and lymphoblastic leukemias. Citation Format: Lina Abdul Karim, Peng Wang, Jose de Guzman, Brandi Higgins, Joeffrey Chahine, Christine Sheehan, Bhaskar Kallakury, Jeffrey S. Ross. PDL1 protein expression and tumor mutation burden in hematologic malignancies: correlation with Hodgkin and high grade lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3724. doi:10.1158/1538-7445.AM2017-3724
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