Castleman disease

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3 regimens on this page
3 variants on this page


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.

HIV-associated multicentric Castleman's disease

Rituximab (Rituxan)

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Regimen

Study Evidence
Gérard et al. 2007 (ANRS 117 CastlemaB) Phase II
Bower et al. 2007 Phase II

Chemotherapy

4-week course

References

  1. 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 contains verified protocol PubMed
  2. 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 contains verified protocol PubMed
  3. Bower M. How I treat HIV-associated multicentric Castleman disease. Blood. 2010 Nov 25;116(22):4415-21. Epub 2010 Aug 5. link to original article PubMed

Multicentric Castleman’s disease

Placebo

Regimen

Study Evidence Comparator Efficacy
van Rhee et al. 2014 Phase III Siltuximab Inferior durable tumor and symptomatic response for at least 18 weeks

No active treatment; all patients did receive "best supportive care."

References

  1. 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 PubMed

Siltuximab (Sylvant)

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Regimen

Study Evidence Comparator Efficacy
van Rhee et al. 2014 Phase III Placebo Superior durable tumor and symptomatic response for at least 18 weeks

Patients had symptomatic, measurable, HIV-negative, and HHV-8-negative multicentric Castleman’s disease (MCD). Note that in the phase I study by Kurzrock et al. the MTD was 12 mg/kg, but the update reports using the 11 mg/kg dosing.

Chemotherapy

Supportive medications

  • All patients received "best supportive care"

21-day cycles, given until treatment failure

Patients in the extension of the phase I study could have their treatment interval lengthened to every 6 weeks if they had a documented PR/CR at 6 months.

References

  1. Phase I: 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. link to original article contains verified protocol PubMed content property of HemOnc.org
    1. 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 PubMed
  2. 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 PubMed

Tocilizumab (Actemra)

Regimen

Study Evidence
Nishimoto et al. 2005 Phase II

Chemotherapy

16-week course; could be extended at physician discretion

References

  1. 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 contains verified protocol PubMed