Tocilizumab for KSHV-Associated Multicentric Castleman Disease

BACKGROUND: * Kaposi sarcoma herpesvirus-associated multicentric Castleman disease (KSHVMCD) is a rare lymphoproliferative disorder that develops predominantly in human immunodeficiency deficiency virus (HIV) infected patients. Patients often have symptoms from interleukin-6 (IL-6), KSHV encoded viral IL-6 (vIL-6), and other cytokines * Goals of therapy include rapid resolution symptoms and elimination of reservoirs of KSHV-infected plasmablasts. * Tocilizumab is a humanized anti-IL-6 receptor (gp80) antibody with activity against MCD unrelated to KSHV (KSHV-negative MCD). While tocilizumab does not directly affect vIL-6 signaling or other KSHV driven pathologic processes, IL-6 overproduction plays a major role in symptoms in KSHV-MCD, and blocking IL-6 may be sufficient to treat this disorder by blocking autocrine and paracrine stimulation. Combination with zidovudine (AZT) and valganciclovir (VGC), agents that target KSHV replication, have virus-activated cytotoxic activity, and are active in KSHV-MCD may be useful and necessary in some patients. OBJECTIVES: * Primary objective: Estimate clinical benefit of tocilizumab 8mg/kg every 2 weeks for up to 12 weeks in patients with symptomatic KSHV-MCD using a modified KSHVMCD Clinical Benefit Response Criteria * Secondary objectives: * Estimate best clinical, biochemical, radiographic, and overall responses in patients with KSHV-MCD treated for up to 12 weeks with tocilizumab 8mg/kg every 2 weeks using the prior National Cancer Institute (NCI) KSHV-MCD Response Criteria. * In patients with inadequate response to tocilizumab monotherapy: explore preliminarily the activity of tocilizumab 8mg/kg every 2 weeks, combined with AZT 600 mg orally q6 hours and VGC 900 mg orally q12 hours on days 1-5 of a 14-day cycle * Evaluate safety and tolerability of tocilizumab alone and combined with AZT/VGC * Evaluate the effect of tocilizumab on the pharmacokinetics of antiretroviral agents that are Cytochrome P450 3A4 (CYP3A4) substrates in patients with symptomatic KSHV-MCD * Evaluate progression-free and overall survival of patients treated with tocilizumab and tocilizumab/AZT/VGC * Evaluate of effect of tocilizumab on KS Eligibility * Pathologically confirmed KSHV-associated MCD * Age greater than or equal to 18 * At least one clinical symptom and at least one laboratory attributable to KSHV-MCD * Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 * No life- or organ-threatening manifestations of MCD * Patients requiring therapy for rheumatoid arthritis will be excluded * HIV-infected patients must agree to continue or start combination antiretroviral therapy DESIGN: * Open label, single center pilot study. Eligible patients receive tocilizumab 8 mg/kg every 2 weeks for up to 12 weeks. In addition, patients requiring treatment intensification also receive AZT 600 mg orally q6 hours and VGC 900 mg orally q12 hours on days 1-5 of a 14-day cycle. * Sample size 17: two stage phase II design, alpha equals beta equals 0.10, ruling out \<20% KSHV-MCD Clinical Benefit Partial Response or better with tocilizumab and targeting a \>50% KSHV-MCD Clinical Benefit Partial Response or better requires 10 in the first stage. 0-2 of 10 major response: stop accrual, 3+/10: accrual to 17 total. * Responses evaluated by KSHV-MCD Clinical Benefit Response Criteria and NCI KSHV-MCD criteria under prospective evaluation. * Safety and tolerability evaluated using current Common Terminology Criteria for Adverse Events (CTCAE).