Background: Kaposi sarcoma herpesvirus (KSHV)-associated multicentric Castleman disease (MCD) is a lymphoproliferative disorder driven by cytokine excess, particularly human and viral interleukin 6 (IL-6). Tocilizumab, a humanized anti-IL-6 receptor (gp80) antibody, has demonstrated benefit in KSHV-negative MCD, although its utility in KSHV-MCD is unknown.

Methods: Patients with HIV and symptomatic KSHV-MCD received 8 mg/kg of tocilizumab every 2 weeks for up to 12 weeks (6 cycles). In the event of progression or lack of improvement with tocilizumab alone, oral zidovudine (AZT) and valganciclovir (VGC) on days 1-5 of a 14-day cycle was administered with tocilizumab. Responses were assessed using a KSHV-MCD clinical benefit response (CBR) criteria, consisting of 4 symptom groups and 4 laboratory parameters. The primary objective was to estimate the response rate of tocilizumab in patients with symptomatic KSHV-MCD using the modified KSHV-MCD CBR criteria.

Results: Eight patients with median age of 48.8 years were enrolled. With tocilizumab alone, the CBR rate for all patients was 63%(95% confidence interval 25% to 92%). Three patients then received AZT and VGC with tocilizumab and all had clinical benefit. The median time to next therapy for all patients was 3.2 months (range 1–37 months).

Conclusion: Tocilizumab as a single agent or in combination with AZT and VGC induced early improvement in symptoms and laboratory findings, but responses were not sustained. Incomplete responses to tocilizumab may occur because tocilizumab binds to the gp80 IL-6 receptor and KSHV vIL-6 can bind to the gp130 receptor subunit without requiring gp80.