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10028 Background: KS is a disease of multi-focal vascular proliferation that requires infection with KS herpes virus (KSHV/HHV-8). KSHV infected cells demonstate activation of the c-kit and platelet derived growth factor (PDGF) receptors. Partial KS regression in 5/10 patients was observed in a pilot study using the c-kit/PDGF-R inhibitor imatinib (Novartis Pharmaceuticals) suggesting this agent has activity in KS.METHODSThe primary objective was to estimate the response rate in AIDS-related KS. Secondary objectives included investigation biomarkers of response and imatinib pharmacokinetics in patients on cART. Plasma concentrations of CCL5, IFNg, IL-6 and FGF-b were measured. Patients were treated with imatinib 400mg/day orally for up to 12 months with the option to dose escalate to 600mg/day at 3 months if disease was stable.RESULTSThirty patients were treated at 12 AMC sites. Median CD4 count was 263 (19-819). 79% had undetectable HIV RNA. Ten (33.3%) showed partial response, 6 (20%) had stable disease and 7 (23.3%) showed KS progression. Nine patients completed 52 weeks of imatinib and the median treatment duration was 22.5 weeks (0.3-52.7). Only 5 patients (16.7%) discontinued therapy due to adverse events including grade 3 hypophosphatemia (2) allergic reaction (1), cellulitis (1), depression (1) and grade 4 elevation of CK (1). Pharmacokinetic analysis of the AUC ratios demonstrated that actual imatinib AUC levels were significantly higher than predicted (P=0.036), but there was no difference between actual and predicted AUC for the active metabolite (P=0.441), suggesting the anti-retroviral regimens influenced imatinib metabolism. Levels of CCL5, IFNg, IL-6 and FGF-b correlated with response in a pilot study; however, none of these growth factors predicted response in this larger study.CONCLUSIONSImatinib has activity in AIDS-related Kaposi's sarcoma. The potential interactions with antiretroviral drugs did not correlate with increased toxicity. Thirty percent of patients showed long-term clinical benefit and remained on imatinib for the entire year. These results suggest this regimen is well tolerated and may be an alternative to cytotoxic chemotherapy for some patients with AIDS-related KS.

Phase II AIDS Malignancy Consortium (AMC) trial of imatinib in AIDS-associated Kaposi’s sarcoma (KS)