Abstract
Human herpes virus type 8 (HHV-8)-negative, idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disease often involving constitutional symptoms, cytopenias, and multiple organ system dysfunction. In China, the majority of MCD cases are HHV-8 negative. Given that siltuximab, the only FDA-approved treatment for iMCD is not available in China; rituximab- and cyclophosphamide-containing regimens are often used in the treatment of Chinese iMCD patients. To evaluate the efficacy of rituximab in this rare and heterogeneous disease, clinical and pathological data from 27 cases of iMCD were retrospectively analyzed from two large medical centers in China. The novel diagnostic criteria for iMCD were applied, and POEMS syndrome, IgG4-related diseases, and follicular dendritic cell sarcomas cases were excluded from analyses. Total response rate of rituximab- and cyclophosphamide-containing regimens was 55.5%, with 33.3% (9/27) of the cases reaching CR and 22.2% (6/27) PR. In the 14 cases of R-R iMCD, total response rate was only 42.9% (CR 14.3% [2/14], PR 28.6% [4/14]). The 5-year OS of these 27 iMCD cases was 81% (95% CI 64–98; 27 total patients, 4 events, 23 censored) after receiving these regimens, but the 5-year PFS was 43% (95% CI 19–66; 25 total patients, 11 events, 14 censored). Thus, rituximab-based regimens should be considered for the treatment of iMCD patients when siltuximab is not available and potentially in siltuximab-refractory cases.
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References
Castleman B, Iverson L, Menendez VP (1956) Localized mediastinal lymph node hyperplasia resembling thymoma. Cancer 9(4):822–830
Casper C (2005) The aetiology and management of Castleman disease at 50 years: translating pathophysiology to patient care. Br J Haematol 129(1):3–17. https://doi.org/10.1111/j.1365-2141.2004.05311.x
Fajgenbaum DC, van Rhee F, Nabel CS (2014) HHV-8-negative, idiopathic multicentric Castleman disease: novel insights into biology, pathogenesis, and therapy. Blood 123(19):2924–2933. https://doi.org/10.1182/blood-2013-12-545087
Fajgenbaum DC, Uldrick TS, Bagg A, Frank D, Wu D, Srkalovic G, Simpson D, Liu AY, Menke D, Chandrakasan S, Lechowicz MJ, Wong RS, Pierson S, Paessler M, Rossi JF, Ide M, Ruth J, Croglio M, Suarez A, Krymskaya V, Chadburn A, Colleoni G, Nasta S, Jayanthan R, Nabel CS, Casper C, Dispenzieri A, Fosså A, Kelleher D, Kurzrock R, Voorhees P, Dogan A, Yoshizaki K, van Rhee F, Oksenhendler E, Jaffe ES, Elenitoba-Johnson KS, Lim MS (2017) International, evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease. Blood 129(12):1646–1657. https://doi.org/10.1182/blood-2016-10-746933
Dong Y, Wang M, Nong L, Wang L, Cen X, Liu W, Zhu S, Sun Y, Liang Z, Li Y, Ou J, Qiu Z, Ren H (2015) Clinical and laboratory characterization of 114 cases of Castleman disease patients from a single centre: paraneoplastic pemphigus is an unfavourable prognostic factor. Br J Haematol 169(6):834–842. https://doi.org/10.1111/bjh.13378
Dong Y, Na J, Lv J, Wang R, Chen X, Li N, Ren H (2009) Clinical and laboratory characterization of a larger cohort of Castleman’s diseases retrospectively collected from a single center. Leuk Lymphoma 50(8):1308–1317. https://doi.org/10.1080/10428190903060095.
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 (2014) Siltuximab for multicentric Castleman’s disease: a randomised, double-blind, placebo-controlled trial. Lancet Oncol 15(9):966–974. https://doi.org/10.1016/S1470-2045(14)70319-5
Xu D, Lv J, Dong Y, Wang S, Su T, Zhou F, Zou W, Zhao M, Zhang H (2012) Renal involvement in a large cohort of Chinese patients with Castleman disease. Nephrol Dial Transplant 27(S3):119–125. https://doi.org/10.1093/ndt/gfr245
Zhang L, Li Z, Cao X, Feng J, Zhong D, Wang S, Zhou D, Li J (2016) Clinical spectrum and survival analysis of 145 cases of HIV-negative Castleman’s disease: renal function is an important prognostic factor. Sci Rep 6:23831. https://doi.org/10.1038/srep23831
Hoffmann C, Schmid H, Müller M, Teutsch C, van Lunzen J, Esser S, Wolf T, Wyen C, Sabranski M, Horst HA, Reuter S, Vogel M, Jäger H, Bogner J, Arasteh K (2011) Improved outcome with rituximab in patients with HIV-associated multicentric Castleman disease. Blood 118(13):3499–3503. https://doi.org/10.1182/blood-2011-02-333633
Yu L, Tu M, Cortes J, Xu-Monette ZY, Miranda RN, Zhang J, Orlowski RZ, Neelapu S, Boddu PC, Akosile MA, Uldrick TS, Yarchoan R, Medeiros LJ, Li Y, Fajgenbaum DC, Young KH (2017) Clinical and pathological characteristics of HIV- and HHV-8-negative Castleman disease. Blood 129(12):1658–1668. https://doi.org/10.1182/blood-2016-11-748855
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 (2016) Clinicopathologic analysis of TAFRO syndrome demonstrates a distinct subtype of HHV-8-negative multicentric Castleman disease. Am J Hematol 91(2):220–226. https://doi.org/10.1002/ajh.24242
Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-López A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP (1999) Report of an international workshop to standardize response criteria for non-Hodgkin’s lymphomas. NCI Sponsored International Working Group. J Clin Oncol 17(4):1244. https://doi.org/10.1200/JCO.1999.17.4.1244
Chang KC, Wang YC, Hung LY, Huang WT, Tsou JH, M Jones D, Song HL, Yeh YM, Kao LY, Medeiros LJ (2014) Monoclonality and cytogenetic abnormalities in hyaline vascular Castleman disease. Mod Pathol 27(6):823–831. https://doi.org/10.1038/modpathol.2013.202
Liu AY, Nabel CS, Finkelman BS, Ruth JR, Kurzrock R, van Rhee F, Krymskaya VP, Kelleher D, Rubenstein AH, Fajgenbaum DC (2016) Idiopathic multicentric Castleman’s disease: a systematic literature review. Lancet Haematol 3(4):e163–e175. https://doi.org/10.1016/S2352-3026(16)00006-5
Casper C, Chaturvedi S, Munshi N, Wong R, Qi M, Schaffer M, Bandekar R, Hall B, van de Velde H, Vermeulen J, Reddy M, van Rhee F (2015) Analysis of inflammatory and anemia-related biomarkers in a randomized, double-blind, placebo-controlled study of siltuximab (anti-IL6 monoclonal antibody) in patients with multicentric Castleman disease. Clin Cancer Res 21(19):4294–4304. https://doi.org/10.1158/1078-0432.CCR-15-0134
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Supplement Table 3
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Supplement Fig. 3
The flowchart of procedure of patients screening. POEMS: POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, Skin pigmentation); SLE: systemic lupus erythematosus; IgG4RD: IgG4-related diseases; FDCS: follicular dendritic cell sarcomas; HHV8: human herpes virus type 8; CN: Chemotherapy naïve iMCD; R-R: Refractory-relapsed iMCD (JPG 214 kb)
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Dong, Y., Zhang, L., Nong, L. et al. Effectiveness of rituximab-containing treatment regimens in idiopathic multicentric Castleman disease. Ann Hematol 97, 1641–1647 (2018). https://doi.org/10.1007/s00277-018-3347-0
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DOI: https://doi.org/10.1007/s00277-018-3347-0