C071 | PATTERNS OF USAGE AND EFFICACY OF SILTUXIMAB IN IDIOPATHIC MULTICENTRIC CASTLEMAN DISEASE IN ITALY

Siltuximab has been approved for the treatment of idiopathic multicentric Castleman disease (iMCD) by the Food and Drug Administration in 2014 and it has been made available in Italy thereafter, initially via a named-patient program. Ten years later, post-commercialization real life results are still very limited in international literature. Purpose of this work is to review the Italian experience with siltuximab, either used as frontline or later-line treatment, in patients with a confirmed diagnosis of iMCD. This represents to the best of our knowledge the widest series of patients treated with siltuximab analyzed so far. Sixty-one patients (38 males and 23 females) received siltuximab between April 2014 and October 2024, at a median age of 61 years (range: 31-83), in 31 cases (50.8%) as their frontline treatment and in 20 cases (32.8%) as a second line (Figure, Panel A). One patient received treatment twice. Disease type was hyaline-vascular in 37.7% of the cases, plasmacytic type in 37.7% and mixed type in 16.4% (unavailable histology in 8.2%). Fatigue (65.5%), malaise (53.5%), weight loss (27.9%) and anorexia (24.6%) were the most frequently reported symptoms before siltuximab. Twenty patients had fever (32.8%), along with generalized edema (30%), ascites or pleural effusion (25% each) and interstitial lung disease (5%). Fifty-five patients had their response evaluated during the course of the treatment, with a response in 64% of the cases. Treatment was interrupted in 31.1% of the patients after a median duration of 9 months, mainly due to disease progression; in the remaining, treatment is still ongoing after a median of 30.6 months. At a median follow-up of 44.8 months, progression-free survival is 80.2% and overall survival is 85.9% (Figure, Panel B). One patient experienced grade 3 neutropenia and 1 patient had grade 2 pancreatic enzyme elevation, both considered drug-correlated. Two patients died because of drug-unrelated venous thrombosis with massive pulmonary embolism. Two patients had secondary neoplasms: a spinocellular carcinoma (arising after previous radiotherapy) and fibrosarcoma. Nine patients received further treatment after siltuximab, including rituximab (4 cases), tocilizumab and chemotherapy (2 each) and lenalidomide (1 case). In conclusion, siltuximab confirms to be the frontline treatment of choice in iMCD, yielding favorable long-term survival rates and excellent disease control over time.