Incorporation of ANTI-HHV-8 Agents as Targeted Therapy for the Treatment of HIV-Associated Primary Effusion Lymphoma.

Abstract Abstract 4768 Background Primary effusion lymphoma (PEL) is a non-Hodgkin lymphoma (NHL) which comprises 4% of all AIDS-related lymphomas. PEL has a predilection for body cavities, causing pleural and pericardial effusions and ascites, but may present as masses. EBV is present in PEL cells in 80% of cases, but HHV-8 infection in PEL cells is required for the diagnosis (dx). Historically, treatment encompassed approaches including intracavitary antiretroviral medications (ARV) or chemotherapeutic agents, single or multi-agent systemic chemotherapy, and systemic ARVs, but median survival in case series using these approaches was only 6 months (mo). Treatment with multi-agent chemotherapy and highly active ARV therapy (HAART) yields good outcome in other HIV-NHL with survival approaching that of the HIV-negative population, but gives unknown survival rates in PEL. Recent consideration has been given to targeted therapy directed against HHV-8 infection with antiviral agents, with encouraging outcomes reported in the literature, particularly the HHV-8 associated syndromes Kaposi Sarcoma (KS) and Multicentric Castleman's Disease. We report on 5 patients (pts) diagnosed with PEL and treated at St. Paul's Hospital, 2 of whom are receiving valganciclovir (VGCV) therapy directed against HHV-8 infection of PEL cells. Methods We conducted a retrospective review of pts with a tissue dx of PEL since 2004. PEL data was collected from the clinical charts and HIV-related data from the BC Centre for Excellence in HIV/AIDS (CFE) database. A literature search was performed to capture prior studies of anti-HHV-8 medications used to treat PEL. Results The median age at PEL diagnosis was 60 (range 48-68) years (y); gender was: male, n=4; and female, n=1. 2 pts had a history of KS. The median CD4 count at PEL dx was 230 (50-560) cells/ml, 1 pt had a CD4 count of 50 cells/ml and all others were ≥210 cells/ml; median HIV viral load (VL; reported in 4) was 81 (35-176,600) copies/ml. The median time from HIV dx to PEL dx was 6 (0-21) y and from initiation of HAART to PEL dx 1 (0-11) y. Clinical PEL presentation was: pleural effusions, n=4; pericardial effusion, n=2; ascites, n=1; associated mass, n=1; mass without effusions, n=1. PEL treatment was: CHOP + HAART, n=2; CHOP + HAART + VGCV, n=1; HAART + VGCF, n=1; supportive care, n=1. 2 pts receiving CHOP and HAART are both in complete remission (CR) at 8 and 57 months (mo) from PEL dx. 2 pts diagnosed since December 2008 are receiving VGCV and HAART, and 1 of these pts is receiving CHOP with good tolerance (the other pt declined cytotoxic chemotherapy). Of 3 pts receiving CHOP, there was 1 episode of febrile neutropenia (FN) in 1 pt and 5 episodes of FN and 3 clinical infections in a second pt. The same pt had profound anemia and thrombocytopenia requiring transfusion support; this pt did not receive VGCV. 1 pt receiving VGCV with HAART and CHOP required G-CSF support but did not develop FN or clinical infection. 1 pt presented with a poor performance status, received supportive care only and died within one mo of PEL dx; all others are alive at 4, 8, 14 and 57 months from PEL dx. A literature review identified 2 reports of pts with PEL receiving systemic cidofovir (CDFV) directed against HHV-8. One pt with a CD4 count of 72 cells/ml and an HIV-VL of 75,000 copies/ml received unspecified systemic chemotherapy, HAART and intravenous (IV) CDFV followed by VGCV and is in CR at 68 mo from PEL dx. A second pt with a CD4 of 498 cells/ml (HIV-VL not reported) received HAART, IV cidofovir and interferon and is in CR at 28 mo. Conclusions PEL treatment has focused on optimization of HIV control with HAART and lymphoma control with chemotherapy, however, antiviral medications as targeted therapy directed against HHV-8 infection of PEL cells may be used without undue toxicity and possibly with success. PEL generally involves latent HHV-8 infection, which is theoretically not susceptible to antiviral medications, but there are reports in the literature of encouraging results achieved by combining agents to induce lytic infection (including chemotherapeutic agents) with anti-herpes virus therapy. Our review indicates good tolerance of VGCV with HAART ± CHOP chemotherapy, and that with newer treatment approaches, pts may live longer than the 6 mo median survival previously reported. To our knowledge, our pts receiving VGCV are the third and fourth pts reported receiving anti-HHV-8 therapy as treatment for PEL. Disclosures: Off Label Use This presentation discusses the use of valganciclovir in the treatment of HHV-8 associated primary effusion lymphoma..

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