Castleman disease

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There are (at least) three distinct entities under this topic: unicentric Castleman's disease (UCD); HHV-8-positive multicentric Castleman's disease (MCD), which is usually (but not always) associated with HIV, and HHV-8-negative a.k.a. idiopathic MCD. UCD is usually treated with surgery or embolization. There are very few prospective trials for these diseases. The first-ever diagnostic criteria for HHV-8-negative "idiopathic" Multicentric Castleman disease can ensure diagnosis is correct and subsequent treatment is appropriate for the diagnosed subtype. You can read the full Diagnostic Criteria article here.
*We have moved How I Treat articles to a dedicated page.
Last updated on 2024-09-06:9 regimens on this page
9 variants on this page
=Guidelines=
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
==CDCN==
*For a list of chemotherapy regimens used plus their references, please visit https://www.cdcn.org/about-castleman-disease/treatments/nonspecific-cytotoxic-immuno-depletion
==International Consensus guidelines==
*2017: Fajgenbaum et al. International, evidence-based consensus diagnostic criteria for HHV-8–negative/idiopathic multicentric Castleman disease EuroPMC
*2018: van Rhee et al. International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease link to PMC article EuroPMC
==NCCN==
*NCCN Guidelines - Castleman Disease
=HIV-associated multicentric Castleman disease, all lines of therapy=
==Rituximab monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Gérard et al. 2007 (ANRS 117 CastlemaB)	2003-03 to 2004-12 	Phase 2
Bower et al. 2007 	2003-2006 	Phase 2
====Targeted therapy====
*Rituximab (Rituxan) 375 mg/m2 IV once on day 1
7-day cycle for 4 cycles (4-week course)
===References===
# ANRS 117 CastlemaB: Gérard L, Bérezné A, Galicier L, Meignin V, Obadia M, De Castro N, Jacomet C, Verdon R, Madelaine-Chambrin I, Boulanger E, Chevret S, Agbalika F, Oksenhendler E. Prospective study of rituximab in chemotherapy-dependent human immunodeficiency virus associated multicentric Castleman's disease: ANRS 117 CastlemaB Trial. J Clin Oncol. 2007 Aug 1;25(22):3350-6. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Bower M, Powles T, Williams S, Davis TN, Atkins M, Montoto S, Orkin C, Webb A, Fisher M, Nelson M, Gazzard B, Stebbing J, Kelleher P. Brief communication: rituximab in HIV-associated multicentric Castleman disease. Ann Intern Med. 2007 Dec 18;147(12):836-9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
=HHV-8-negative/"Idiopathic" multicentric Castleman disease, all lines of therapy=
The first-ever diagnostic criteria for HHV-8-negative "idiopathic" multicentric Castleman disease was published in Blood in 2017. You can read the full PMC article here.
==Anakinra monotherapy==
===Regimen===
Study 	Evidence
Galeotti et al. 2008	Case report
====Immunosuppressive therapy====
*Anakinra (Kineret) 1 mg/kg SC once per day
Continued indefinitely
===References===
# Case report: Galeotti C, Tran TA, Franchi-Abella S, Fabre M, Pariente D, Koné-Paut I. IL-1RA agonist (anakinra) in the treatment of multifocal castleman disease: case report. J Pediatr Hematol Oncol. 2008 Dec;30(12):920-4. link to original article EuroPMC
==Bortezomib monotherapy==
===Regimen===
Study 	Evidence
Hess et al. 2006	Case report
====Targeted therapy====
*Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
21-day cycle for 6 cycles
===References===
# Case report: Hess G, Wagner V, Kreft A, Heussel CP, Huber C. Effects of bortezomib on pro-inflammatory cytokine levels and transfusion dependency in a patient with multicentric Castleman disease. Br J Haematol. 2006 Sep;134(5):544-5. link to original article EuroPMC
# Review: Fajgenbaum DC, van Rhee F, Nabel CS. HHV-8-negative, idiopathic multicentric Castleman disease: novel insights into biology, pathogenesis, and therapy. Blood. 2014 May 8;123(19):2924-33. Epub 2014 Mar 12. link to original article EuroPMC
==Cyclosporine monotherapy==
===Regimen===
Study 	Evidence
Inoue et al. 2013	Case report
====Immunosuppressive therapy====
*Cyclosporine A
===References===
# Case report: Inoue M, Ankou M, Hua J, Iwaki Y, Hagihara M, Ota Y. Complete resolution of TAFRO syndrome (thrombocytopenia, anasarca, fever, reticulin fibrosis and organomegaly) after immunosuppressive therapies using corticosteroids and cyclosporin A : a case report. J Clin Exp Hematop. 2013;53(1):95-9. link to original article EuroPMC
==Rituximab monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Ide et al. 2006	2001-2004 	Retrospective
====Targeted therapy====
*Rituximab (Rituxan) 375 mg/m2 IV once on day 1
7-day cycle for 4 to 8 cycles 
====Subsequent treatment====
*After the rituximab administration, oral prednisolone (15 mg/d, tapered to 5 mg/d) and/or alkylating agent (cyclophosphamide 100 mg/day or melphalan 2 mg/d) were started for maintenance therapy
===References===
# Retrospective: Ide M, Kawachi Y, Izumi Y, Kasagi K, Ogino T. Long-term remission in HIV-negative patients with multicentric Castleman's disease using rituximab. Eur J Haematol. 2006 Feb;76(2):119-23. link to original article EuroPMC
# Review: Fajgenbaum DC, van Rhee F, Nabel CS. HHV-8-negative, idiopathic multicentric Castleman disease: novel insights into biology, pathogenesis, and therapy. Blood. 2014 May 8;123(19):2924-33. Epub 2014 Mar 12. link to original article EuroPMC
==Siltuximab monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator	Comparative Efficacy
Kurzrock et al. 2013 (CR008566)	2005-06 to 2009-09 	Phase 1, >20 pts 	 	
van Rhee et al. 2014 (CR016705)	2010-02-09 to 2012-02-03	Randomized Phase 2 (E-RT-esc)	Placebo 	Higher durable tumor and symptomatic response for at least 18 weeks (primary endpoint)
Note: Patients had symptomatic, measurable, HIV-negative, and HHV-8-negative multicentric Castleman disease (MCD). Note that in the phase 1 study by Kurzrock et al. the MTD was 12 mg/kg, but the update reports using the 11 mg/kg dosing.
====Immunosuppressive therapy====
*Siltuximab (Sylvant) 11 mg/kg IV over 60 minutes once on day 1
====Supportive therapy====
*All patients received "best supportive care"
21-day cycles
Patients in the extension of the phase 1 study could have their treatment interval lengthened to every 6 weeks if they had a documented PR/CR at 6 months.
===References===
# CR008566: Kurzrock R, Voorhees PM, Casper C, Furman RR, Fayad L, Lonial S, Borghaei H, Jagannath S, Sokol L, Usmani SZ, van de Velde H, Qin X, Puchalski TA, Hall B, Reddy M, Qi M, van Rhee F. A phase I, open-label study of siltuximab, an anti-IL-6 monoclonal antibody, in patients with B-cell non-Hodgkin lymphoma, multiple myeloma, or Castleman disease. Clin Cancer Res. 2013 Jul 1;19(13):3659-70. Epub 2013 May 9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC content property of HemOnc.org NCT00412321
## Update: van Rhee F, Casper C, Voorhees PM, Fayad LE, van de Velde H, Vermeulen J, Qin X, Qi M, Tromp B, Kurzrock R. A phase 2, open-label, multicenter study of the long-term safety of siltuximab (an anti-interleukin-6 monoclonal antibody) in patients with multicentric Castleman disease. Oncotarget. 2015 Oct 6;6(30):30408-19. link to original article link to PMC article EuroPMC
# CR016705: van Rhee F, Wong RS, Munshi N, Rossi JF, Ke XY, Fosså A, Simpson D, Capra M, Liu T, Hsieh RK, Goh YT, Zhu J, Cho SG, Ren H, Cavet J, Bandekar R, Rothman M, Puchalski TA, Reddy M, van de Velde H, Vermeulen J, Casper C. Siltuximab for multicentric Castleman's disease: a randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2014 Aug;15(9):966-74. Epub 2014 Jul 17. Erratum in: Lancet Oncol. 2014 Sep;15(10):417. link to original article EuroPMC NCT01024036
==Sirolimus monotherapy==
===Regimen===
Study 	Evidence
Iwaki et al. 2016	Case report
====Immunosuppressive therapy====
*Sirolimus (Rapamune)
===References===
# Case report: Iwaki N, Fajgenbaum DC, Nabel CS, Gion Y, Kondo E, Kawano M, Masunari T, Yoshida I, Moro H, Nikkuni K, Takai K, Matsue K, Kurosawa M, Hagihara M, Saito A, Okamoto M, Yokota K, Hiraiwa S, Nakamura N, Nakao S, Yoshino T, Sato Y. Clinicopathologic analysis of TAFRO syndrome demonstrates a distinct subtype of HHV-8-negative multicentric Castleman disease. Am J Hematol. 2016 Feb;91(2):220-6. link to original article EuroPMC
==TCP==
TCP: Thalidomide, Cyclophosphamide, Prednisone
===Regimen===
Study 	Dates of enrollment	Evidence
Zhang et al. 2019 (ZS-1159)	2015-06 to 2018-06 	Phase 2
====Targeted therapy====
*Thalidomide (Thalomid) 100 mg PO once per day
====Chemotherapy====
*Cyclophosphamide (Cytoxan) as follows:
**Cycles 1 to 52: 300 mg/m2 PO once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) as follows:
**Cycles 1 to 52: 1 mg/kg PO once per day on days 1 & 4
7-day cycle for 104 cycles (2 years)
===References===
# ZS-1159: Zhang L, Zhao AL, Duan MH, Li ZY, Cao XX, Feng J, Zhou DB, Zhong DR, Fajgenbaum DC, Li J. Phase 2 study using oral thalidomide-cyclophosphamide-prednisone for idiopathic multicentric Castleman disease. Blood. 2019 Apr 18;133(16):1720-1728. Epub 2019 Feb 13. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT03043105
==Tocilizumab monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence
Nishimoto et al. 2005	2001-07-19 to 2001-10-11	Phase 2
====Immunosuppressive therapy====
*Tocilizumab (Actemra) 8 mg/kg IV once on day 1
14-day cycle for 8 cycles; could be extended at physician discretion
===References===
# Nishimoto N, Kanakura Y, Aozasa K, Johkoh T, Nakamura M, Nakano S, Nakano N, Ikeda Y, Sasaki T, Nishioka K, Hara M, Taguchi H, Kimura Y, Kato Y, Asaoku H, Kumagai S, Kodama F, Nakahara H, Hagihara K, Yoshizaki K, Kishimoto T. Humanized anti-interleukin-6 receptor antibody treatment of multicentric Castleman disease. Blood. 2005 Oct 15;106(8):2627-32. Epub 2005 Jul 5. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
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