Siltuximab is associated with improved progression-free survival in idiopathic multicentric Castleman disease

Abstract Idiopathic multicentric Castleman disease (iMCD) is a rare heterogeneous disorder involving multicentric lymphadenopathy, systemic inflammation, and cytokine-driven organ dysfunction. Despite the approval of siltuximab, a monoclonal antibody against interleukin-6, for the treatment of iMCD, it is not known how long patients should receive siltuximab before determining whether the treatment is beneficial and should be continued. We performed post hoc analyses of the phase 2 randomized double-blind placebo-controlled trial of siltuximab for the treatment of patients with iMCD to determine the sequence of normalization of laboratory, clinical, and lymph node responses in patients who responded to siltuximab. Seventy-nine patients were enrolled in the trial (siltuximab, n = 53; placebo plus best supportive care, n = 26). Progression-free survival (PFS) was significantly improved in siltuximab-treated patients compared with those receiving placebo (P = .0001). The median PFS was 14.5 months (95% confidence interval, 13.6 months to upper bound not reached) for patients receiving placebo but was not reached for patients receiving siltuximab. In siltuximab-treated patients who achieved durable tumor (radiologic) and symptomatic responses (18 [34%] of 53), the median time to normalization of abnormal laboratory tests and clinical end points occurred in the following sequence: thrombocytosis, symptomatic response, elevated C-reactive protein, hypoalbuminemia, anemia, lymph node response, hyperfibrinogenemia, and elevated immunoglobulin G. Siltuximab treatment prolongs PFS, rapidly improves symptomatology, and provides meaningful clinical benefit despite some laboratory tests and enlarged lymph nodes taking months to normalize in treatment responders. These data support the continued frontline use of siltuximab for iMCD, as recommended by international guidelines. This trial was registered at www.clinicaltrials.gov as #NCT01024036.