Characteristics and outcomes of Kaposi sarcoma herpesvirus-associated inflammatory cytokine syndrome.

abstractKaposi sarcoma-associated herpesvirus (KSHV) inflammatory cytokine syndrome (KICS) is characterized by KSHV infection and severe inflammatory symptoms and signs (elevated cytokines, C-reactive protein, and KSHV viremia), without evidence of other causes. The primary objective of this study was to evaluate KICS natural history after exclusion of other inflammatory disorders, including multicentric Castleman disease (MCD) and, per a revised working definition, primary effusion lymphoma (PEL). Participants with KICS were treated for concurrent Kaposi sarcoma (KS) and/or received KICS-directed treatment with targeted therapies used in other KSHV-associated disorders (KAD), such as rituximab, tocilizumab, or high-dose valganciclovir/azidothymidine. KICS response was evaluated using the Clinical Benefit Response Criteria (KICS-CBR). Baseline inflammatory cytokines were compared between those with KICS and participants with other KAD. Seventy-three participants were enrolled from 2011 to 2022. Following exclusion of other inflammatory processes, 35 (34 with HIV) had KICS, and all but 1 had concurrent stage T1 KS. Among participants with KICS, 11 (43%) received rituximab (with liposomal doxorubicin [8] or paclitaxel [3] for concurrent KS) and 55% (95% confidence interval [CI], 23%-83%) had a response per KICS-CBR. Interleukin-10 (IL-10), IL-6, and IL-1β levels were higher among those with KICS than those with KS alone. The median overall survival among participants with KICS was 5.7 years (95% CI, 5.7 years to not reached). KICS is a diagnosis of exclusion from PEL and MCD. Nearly all patients with KICS have advanced KS, and the syndrome is associated with significant morbidity and mortality. Rituximab may benefit a subset of participants with KICS. This trial was registered at www.clinicaltrials.gov as #NCT01419561.