Higher rate of progression in HIV– than in HIV+ patients after rituximab for HHV8+ multicentric Castleman disease

Rituximab has revolutionized treatment of KSHV/HHV8 associated multicentric Castleman disease (HHV8+ MCD), converting a rapidly fatal illness into a relapsing disease. HHV8+ MCD mainly affects HIV-infected patients but can also be observed in HIV-uninfected patients. We retrospectively analysed a cohort of 99 patients (73 HIV+, 26 HIV-) with HHV8+ MCD treated with rituximab-based therapy. Baseline characteristics were similar in HIV- and HIV+ patients although HIV- patients were older (65 vs 42 years) and presented less frequently with Kaposi sarcoma (15% vs 40%). Ninety-five patients (70 HIV+, 25 HIV-) achieved complete remission (CR) after rituximab-based therapy. After a median follow-up of 51 months, 36 patients (12 HIV-, 24 HIV+) experienced disease progression. The 5-year progression-free survival (PFS) was 54 % [Confidence interval (CI) 95%, 41-66]. The 5-year PFS was lower in HIV- patients than in HIV+ patients : 26 % [CI95%, 5-54] and 62% [CI95%, 46-74], respectively (p=0.02 ). A multivariate prognostic factors analysis including time-dependent covariates revealed that HIV negative status, reoccurrence of HHV8 DNA above 3 logs copies/mL and CRP above 20 mg/mL were independently associated with an increased risk of progression after rituximab-induced CR (p=0.001, p=0.01 and p=0.01, respectively). The lower rate of progression observed in the HIV+ population despite a longer follow-up period may result from the possible immune restoration upon antiretroviral therapy. HHV8 viral load and serum CRP monitoring after rituximab therapy, provides information on the progression risk and may help in the decision to resume specific therapy.