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An indirect comparison was conducted between rituximab-based regimens and siltuximab using single-arm meta-analysis and a generalized linear mixed model across five clinical endpoints (CR, PR, ORR, 2-year PFS, and 2-year OS). Patient data were extracted from 14 siltuximab cohort/phase I-II trials (n=387) and six rituximab cohort studies (n=138). Response rates and depth were similar, while 2-year PFS favored siltuximab monotherapy; the model estimated OR=0.358 (95% CI 0.147–0.873, p=0.027), indicating improved odds of achieving 2-year PFS.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/siltuximab-monotherapy-improves-progression-free-survival-compared-to-rituximab-based-therapies-in-patients-with-idiopathic-multicentric-castleman-disease/430326/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/siltuximab-monotherapy-improves-progression-free-survival-compared-to-rituximab-based-therapies-in-patients-with-idiopathic-multicentric-castleman-disease/430326.png","ImageObject",300,407,{"name":92,"@type":93},"Valentina","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-06","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What question does the study address about idiopathic multicentric Castleman disease (iMCD)?","Question",{"text":113,"@type":114},"It compares outcomes from siltuximab monotherapy versus rituximab-based regimens in iMCD using an indirect comparison of published single-arm data.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Which endpoints were compared between the two treatment approaches?",{"text":118,"@type":114},"The study compared CR, PR, ORR, 2-year PFS, and 2-year OS as clinical end-points.",{"name":120,"@type":111,"acceptedAnswer":121},"What were the main findings regarding response rates and 2-year progression-free survival?",{"text":122,"@type":114},"Overall response rates and depth of response were similar, but 2-year PFS was significantly better with siltuximab monotherapy, with an odds ratio favoring siltuximab (OR 0.358, p=0.027).","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},430326,1790765061,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":34,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},13056703020460,"https://ap-avatar.wpscdn.com/avatar/be000253dac470eee5d?_k=1778207105932848923","Annals of Hematology (2025) 104:6229–6235  \n[https://doi.org/10.1007/s00277-025-06560-2](https://doi.org/10.1007/s00277-025-06560-2)  \nRESEARCH  \nSiltuximab monotherapy improves progression free survival compared to rituximab-based therapies in patients with idiopathic multicentric Castleman disease; indirect comparison of studies using single-arm metanalysis method and the generalized linear mixed model  \nLazaros Karatisidis1 · Theodoros Mprotsis2 · Stergios Intzes1 · Konstantinos Zagoridis2 · Georgios Vrachiolias1 · Vera Karatisidou3 · Zoi Bezirgianidou1 · Konstantinos Liapis1 · Ioannis Kotsianidis1 · Emmanouil Spanoudakis1  \nReceived: 24 January 2025 / Accepted: 7 August 2025 / Published online: 5 December 2025 © The Author(s) 2025  \nAbstract  \nSiltuximab is the only approved treatment for idiopathic multicentric Castleman Disease but in many countries the only available treatment is rituximab based. We are performing an indirect comparison of rituximab-based regimens (RBR) and siltuximab by using single arm meta-analysis and the generalized linear mixed model methods comparing outcome in five significant clinical end-points (CR, PR, ORR, 2ysPFS and 2ysOS) . Patient’s data were extracted from 14 cohort or phase I and II trials conducted with siltuximab (n= 387 pts) and six cohort studies treating iMCD patients with rituximab (n= 138 pts) . Response rates and depth of response is similar between the two arms of the study but 2ys PFS is significantly better with siltuximab monotherapy. Using the generalized linear mixed model in order to provide an indirect comparison of odds to achieve the 2yPFS end-point, the reported OR is 0,358, 95% CI (0,147-0,873) and p = 0,027 favoring siltuximab over rituximab-based regimens (RBR) . This is the major finding of our study and to our knowledge is the first time that in a big cohort of patients siltuximab is proved more effective compared to RBR.  \nKeywords Idiopathic multicentric castleman disease · Siltuximab · Rituximab  \nIntroduction  \nCastleman disease (CD) entails a wide spectrum of uncontrolled lymphoproliferative disorders that are related by sharing a spectrum of common characteristic and  \n􀀍 Lazaros Karatisidis [lazaroskaratisidis@gmail.com](lazaroskaratisidis@gmail.com)  \nEmmanouil Spanoudakis  \n[espanoud@med.duth.gr](espanoud@med.duth.gr)  \n1 Department of Hematology, Democritus University of Thrace, Medical School, Alexandroupolis, Greece  \n2 Department of Biomathematics, University of Thessaly, School of Medicine, Larissa, Greece  \n3 The 4th Department of Pediatrics, School of Medicine, Aristotle University of Thessaloniki, General “Papageorgiou”Hospital, Thessaloniki, Greece  \nhistopathological features, but also appears a wide range of etiologies, clinical features and outcomes [1] .  \nUncontrolled HHV8/KSV infection is the etiology of HHV8-MCD (multicentric Castleman disease) that usually occurs in HIV infected immune-compromised hosts. Amongst them, HHV8 can replicate in lymph node plasmablasts and transcribe the viral homolog of interleukin-6 (vIL-6) up-regulating human IL-6 and causing a cytokine storm [2, 3] . Rituximab, as monotherapy or in combination with chemotherapy, is highly effective by depleting B cells, the primary HHV-8 reservoir, leading to a 92% 5-year overall survival [4] .  \nThe etiology and pathogenesis of HHV-8 negative/ iMCD is ill defined. Although iMCD etiology remains elusive, upregulated interleukin-6 (IL-6) signaling is a strong pathogenetic drive [5] . IL-6 is not universally elevated iniMCD, and approximately one-half ofiMCD patients do not respond to IL-6 inhibition therapy [2, 5, 6] .  \nCurrently, iMCD is diagnosed when a constellation of nonspecific but characteristic lymph node histopathologic  \nfeatures, commonly described as “hyaline vascular,”“plasmacytic,” or “mixed”, are observed in patients with appropriate clinical features [2] . Major Criterion 1 requires histopathologic features consistent with iMCD on an excisional lymph node bi","cbCaieEJawiA03oB","https://ap.wps.com/l/cbCaieEJawiA03oB","pdf",1132583,"English","# Abstract\n# Introduction\n# Materials and methods","[{\"question\":\"What question does the study address about idiopathic multicentric Castleman disease (iMCD)?\",\"answer\":\"It compares outcomes from siltuximab monotherapy versus rituximab-based regimens in iMCD using an indirect comparison of published single-arm data.\"},{\"question\":\"Which endpoints were compared between the two treatment approaches?\",\"answer\":\"The study compared CR, PR, ORR, 2-year PFS, and 2-year OS as clinical end-points.\"},{\"question\":\"What were the main findings regarding response rates and 2-year progression-free survival?\",\"answer\":\"Overall response rates and depth of response were similar, but 2-year PFS was significantly better with siltuximab monotherapy, with an odds ratio favoring siltuximab (OR 0.358, p=0.027).\"}]","Siltuximab monotherapy improves progression free survival compared to rituximab-based therapies in patients with idiopathic multicentric Castleman disease | PDF",1790652544,18]