IMMUNE AND VIRUS‐SPECIFIC RESPONSES IN PARTICIPANTS WITH PRIMARY EFFUSION LYMPHOMA RECEIVING LENALIDOMIDE, DOSE‐ADJUSTED EPOCH, AND RITUXIMAB (EPOCH‐R2) (2021)

Background: Primary effusion lymphoma (PEL) is an aggressive HIV-associated B cell lymphoma caused by Kaposi sarcoma herpesvirus (KSHV, human herpesvirus 8). We presented safety data of a prospective phase 1 of dose-adjusted etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone with rituximab and lenalidomide (EPOCH-R2) in untreated PEL at the ASH Annual Meeting 2020 (Abstract 2105). 6 HIV+ cisgender men received antiretroviral therapy, lenalidomide 25 mg days 1-10, and EPOCH-R for 6 cycles. 3 participants (pts) had complete responses (responders); 3 had progressive/stable disease (non-responders) at end-of-treatment (EOT). Methods: We performed flow cytometry evaluating T cell subsets, monocytes (monos), and neutrophils at baseline (BL), post-cycle 1 (C1), post-cycle 4 (C4), EOT, and 1-year post-EOT (YR1). KSHV and CMV/EBV/influenza-specific T cell responses were measured using an interferon-gamma (IFN-g) ELISPOT assay at BL, EOT, and YR1. We determined breadth of virus-specific responses by the number of KSHV open reading frames (ORFs) eliciting IFN-g responses and intensity of responses by mean spot forming units (SFUs) per 106 PBMCs. Comparisons were evaluated by Wilcoxon rank sum and Spearman correlation. Results: At BL, responders had a higher percentage of inflammatory tissue factor (TF)+ CD14+ monos compared with non-responders (median [med] 30% vs 10%, p = 0.049), higher percentage of PD-1+ CD4+ effector memory (CD27-CD45RO+) T (TEM) cells (med 90% vs 71%, p = 0.049), and lower percentage of CD38+ CD8+ TEM cells (med 75% vs 96%; p = 0.049). Responders had a decrease in TF+ CD14+ monos from BL to C1 and C4 (p = 0.049 and 0.049) and decrease in PD-L1+ CD14+ monos from BL to C1 (p = 0.049) compared to non-responders. PD-L1 expression on monos and neutrophils was strongly correlated (r = 0.74), and TF and PD-L1 expression on monos was correlated (r = 0.45) when analyzing EOT and YR1 changes from BL. KSHV ORF reactivity was variable across pts with no differences in breadth or intensity between response groups. KSHV-specific responses strongly correlated with EOT and YR1 changes from BL in CD8 counts (r = 0.86) and negatively correlated with EOT and YR1 changes from BL in PD-L1 expression on monos and neutrophils (r = -0.57 and -0.69). The research was funded by: the Intramural Research Program of the NIH, National Cancer Institute and by US federal funds from the National Cancer Institute, National Institutes of Health, under Contract No.HHSN261200800001E. Keywords: Diagnostic and Prognostic Biomarkers, Aggressive B-cell non-Hodgkin lymphoma, Combination Therapies Conflicts of interests pertinent to the abstract K. Lurain Research funding: BMS-Celgene through CRADA with the NCI R. Ramaswami Research funding: BMS-Celgene through CRADA with the NCI T. S. Uldrick Research funding: BMS-Celgene through CRADA with the NCI Other remuneration: Co-inventor on US Patent 10,001,483 D. Whitby Other remuneration: Co-inventor on US Patent 10,001,483 R. Yarchoan Research funding: BMS-Celgene through CRADA with NCI Other remuneration: Co-inventor on US Patent 10,001,483