Abstract
A 57-year-old male with acute-type adult T cell leukemia–lymphoma (ATL) developed persistent watery, non-bloody diarrhea at a volume of 2–3 L/day following the administration of the anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, mogamulizumab. An extensive examination revealed the absence of any pathogenic bacteria or parasites in his stool. Biopsied specimens from the colonic mucosa contained many small nests of apoptotic bodies in the colonic glands, which mimicked acute-colonic graft-versus-host disease. Activation of the auto-reactive immune system due to the depletion of regulatory T-cells by mogamulizumab was suspected as causative. Special attention should be paid to the risk of unique immune-related adverse events induced by mogamulizumab.
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References
Ishitsuka K, Tamura K. Human T-cell leukaemia virus type I and adult T-cell leukaemia-lymphoma. Lancet Oncol. 2014;15:e517–26.
Yoshie O, Fujisawa R, Nakayama T, Harasawa H, Tago H, Izawa D, et al. Frequent expression of CCR4 in adult T-cell leukemia and human T-cell leukemia virus type 1-transformed T cells. Blood. 2002;99:1505–11.
Ishida T, Inagaki H, Utsunomiya A, Takatsuka Y, Komatsu H, Iida S, et al. CXC chemokine receptor 3 and CC chemokine receptor 4 expression in T-cell and NK-cell lymphomas with special reference to clinicopathological significance for peripheral T-cell lymphoma, unspecified. Clin Cancer Res. 2004;10:5494–500.
Ishida T, Joh T, Uike N, Yamamoto K, Utsunomiya A, Yoshida S, et al. Defucosylated anti-CCR4 monoclonal antibody (KW-0761) for relapsed adult T-cell leukemia-lymphoma: a multicenter phase II study. J Clin Oncol. 2012;30:837–42.
Ogura M, Ishida T, Hatake K, Taniwaki M, Ando K, Tobinai K, et al. Multicenter phase II study of mogamulizumab (KW-0761), a defucosylated anti-cc chemokine receptor 4 antibody, in patients with relapsed peripheral T-cell lymphoma and cutaneous T-cell lymphoma. J Clin Oncol. 2014;32:1157–63.
Shinkawa T, Nakamura K, Yamane N, Shoji-Hosaka E, Kanda Y, Sakurada M, et al. The absence of fucose but not the presence of galactose or bisecting N-acetylglucosamine of human IgG1 complex-type oligosaccharides shows the critical role of enhancing antibody-dependent cellular cytotoxicity. J Biol Chem. 2003;278:3466–73.
Ishii T, Ishida T, Utsunomiya A, Inagaki A, Yano H, Komatsu H, et al. Defucosylated humanized anti-CCR4 monoclonal antibody KW-0761 as a novel immunotherapeutic agent for adult T-cell leukemia/lymphoma. Clin Cancer Res. 2010;16:1520–31.
Katsuya H, Yamanaka T, Ishitsuka K, Utsunomiya A, Sasaki H, Hanada S, et al. Prognostic index for acute- and lymphoma-type adult T-cell leukemia/lymphoma. J Clin Oncol. 2012;30:1635–40.
Sugiyama D, Nishikawa H, Maeda Y, Nishioka M, Tanemura A, Katayama I, et al. Anti-CCR4 mAb selectively depletes effector-type FoxP3+CD4+ regulatory T cells, evoking antitumor immune responses in humans. Proc Natl Acad Sci USA. 2013;110:17945–50.
Kato K, Miyamoto T, Numata A, Nakaike T, Oka H, Yurino A, et al. Diffuse panbronchiolitis after humanized anti-CCR4 monoclonal antibody therapy for relapsed adult T-cell leukemia/lymphoma. Int J Hematol. 2013;97:430–2.
Nakano N, Kusumoto S, Tanaka Y, Ishida T, Takeuchi S, Takatsuka Y, et al. Reactivation of hepatitis B virus in a patient with adult T-cell leukemia-lymphoma receiving the anti-CC chemokine receptor 4 antibody mogamulizumab. Hepatol Res. 2014;44:354–7.
Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711–23.
Robert C, Thomas L, Bondarenko I, O’Day S, Weber J, Garbe C, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364:2517–26.
Ferrara JL, Levine JE, Reddy P, Holler E. Graft-versus-host disease. Lancet. 2009;373:1550–61.
Edinger M, Hoffmann P, Ermann J, Drago K, Fathman CG, Strober S, et al. CD4+CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation. Nat Med. 2003;9:1144–50.
Di Ianni M, Falzetti F, Carotti A, Terenzi A, Castellino F, Bonifacio E, et al. Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation. Blood. 2011;117:3921–8.
Ishida T, Ito A, Sato F, Kusumoto S, Iida S, Inagaki H, et al. Stevens-Johnson Syndrome associated with mogamulizumab treatment of adult T-cell leukemia/lymphoma. Cancer Sci. 2013;104:647–50.
Patey-Mariaud de Serre N, Canioni D, Ganousse S, Rieux-Laucat F, Goulet O, Ruemmele F, et al. Digestive histopathological presentation of IPEX syndrome. Mod Pathol. 2009;22:95–102.
Wilgenhof S, Neyns B. Anti-CTLA-4 antibody-induced Guillain–Barre syndrome in a melanoma patient. Ann Oncol. 2011;22:991–3.
Bompaire F, Mateus C, Taillia H, De Greslan T, Lahutte M, Sallansonnet-Froment M, et al. Severe meningo–radiculo–neuritis associated with ipilimumab. Invest New Drugs. 2012;30:2407–10.
Manousakis G, Koch J, Sommerville RB, El-Dokla A, Harms MB, Al-Lozi MT, et al. Multifocal radiculoneuropathy during ipilimumab treatment of melanoma. Muscle Nerve. 2013;48:440–4.
Acknowledgments
KI, MM, HK, AM, MM, CK, TG, MI, YI, YT, HI, and KT treated the patients. SN and MT performed pathological examination. KI wrote the paper. All authors approved the submitted and final version of this manuscript.
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Ishitsuka, K., Murahashi, M., Katsuya, H. et al. Colitis mimicking graft-versus-host disease during treatment with the anti-CCR4 monoclonal antibody, mogamulizumab. Int J Hematol 102, 493–497 (2015). https://doi.org/10.1007/s12185-015-1811-3
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DOI: https://doi.org/10.1007/s12185-015-1811-3