Colitis mimicking graft-versus-host disease during treatment with the anti-CCR4 monoclonal antibody, mogamulizumab

Ishitsuka, Kenji; Murahashi, Mutsunori; Katsuya, Hiroo; Mogi, Ai; Masaki, Michio; Kawai, C; Gotō, Tetsuo; Ishizu, Masanao; Ikari, Y.; Takamatsu, Yasushi; Ishibashi, Hideki; Nimura, Satoshi; Takeshita, Morishige; Tamura, Kazuo

doi:10.1007/s12185-015-1811-3

Cited by 14 publications

(6 citation statements)

References 23 publications

(16 reference statements)

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“…12 There is a report of a patient in whom a severe, treatment-refractory colitis developed during treatment with mogamulizumab, which further highlights the impact of depletion of Treg cells and loss of tolerance of cutaneous and enteric commensal organisms. 13 The MAR noted in our patient had a primarily granulomatous histologic pattern, with a clinical presentation resembling Malassezia-driven head and neck dermatitis, as observed in patients with severe atopic dermatitis. Itraconazole and azole antifungals were effective treatments in more than two thirds of adult patients with head and neck dermatitis on atopic skin background 14 and also were found to be effective in our patient.…”

Section: Discussionsupporting

confidence: 61%

Effective treatment of mogamulizumab-induced head and neck dermatitis with fluconazole in a patient with peripheral T-Cell lymphoma

et al. 2022

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Section: Discussionsupporting

confidence: 61%

Effective treatment of mogamulizumab-induced head and neck dermatitis with fluconazole in a patient with peripheral T-Cell lymphoma

et al. 2022

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“…In ulcerative colitis, adoptively transferred CCR4-deficient Tregs fail to inhibit T cell proliferation due to delayed migration 40 . In turn, treatment of adult T-cell lymphoma with the CCR4 antibody mogamulizumab can cause colitis mimicking GvHD, which is suspected to be due to Treg depletion 29 . Therefore, the protective capacity of Tregs should be considered when targeting CCR4 in GvHD.…”

Section: Discussionmentioning

confidence: 99%

The CCR4/CCL17 axis drives intestinal acute Graft versus Host disease after allogeneic bone marrow transplantation

Schlaweck,

Klesse,

Schanz

et al. 2024

Preprint

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Acute-Graft-versus-Host disease (aGvHD) is a life-threatening complication after allogeneic stem-cell-transplantation. It is mediated by alloreactive T cells whose trafficking to aGvHD target organs is orchestrated by chemokines. We here asked whether CCL17 and its corresponding receptor CCR4 are involved in aGvHD development and severity. We applied an experimental mouse model of aGvHD in CCR4/CCL17 knockout mice and analyzed gut biopsies of GvHD patients. We show that the absence of CCR4 in transplanted T cells induced significantly less severe aGvHD. This was accompanied by reduced expression of Gata3. Mechanistically, only CD4+, but not CD8+CCR4-/- T cells protected from aGvHD. We next identified dendritic cells in the small intestine to produce CCL17, which selectively recruited CD4+ T cells. IL-4 production by intestinal CD4+ T cells promoted proliferation of CD8+ T cells. In line, we detected an upregulation of CCL17 and Gata3 in human aGvHD samples. Our results indicate that local CCL17 production in aGvHD target organs recruits T cells, reinforcing local tissue damage and immune cell recruitment. We identified the JAK1/2-inhibitor ruxolitinib to dampen CCL17-expression, thereby reducing GvHD severity. We here dissect a to date unknown role of the CCL17-CCR4 axis in aGvHD, which might help to develop novel therapeutic strategies.

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“…Thus, strategies to improve the outcomes of allo-HSCT preceded by MOG treatment are needed. Because MOG is a potent anti-ATLL agent and will be used to treat other T cell malignancies, future studies should be aimed at developing new treatment protocols integrating MOG at a suitable dose and with proper timing of administration to minimize GVHD and enhance the GvATLL effect [44][45][46][47].…”

Section: Discussionmentioning

confidence: 99%

Mogamulizumab Treatment Prior to Allogeneic Hematopoietic Stem Cell Transplantation Induces Severe Acute Graft-versus-Host Disease

Sugio

Katô

Aoki

et al. 2016

Biology of Blood and Marrow Transplantation

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Mogamulizumab (MOG), a humanized anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, has recently played an important role in the treatment of adult T cell leukemia/lymphoma (ATLL). Because CCR4 is expressed on normal regulatory T cells as well as on ATLL cells, MOG may accelerate graft-versus-host disease (GVHD) by eradicating regulatory T cells in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, there is limited information about its safety and efficacy in patients treated with MOG before allo-HSCT. In the present study, 25 patients with ATLL were treated with MOG before allo-HSCT, after which 18 patients (72%) achieved remission. The overall survival and progression-free survival at 1 year post-transplantation were 20.2% (95% CI, 6.0% to 40.3%) and 15.0% (95% CI, 4.3% to 32.0%), respectively. The cumulative incidence of acute GVHD was 64.0% (95% CI, 40.7% to 80.1%) for grade II-IV and 34.7% (95% CI, 15.8% to 54.4%) for grade III-IV. The cumulative incidence of transplantation-related mortality (TRM) was 49.0% (95% CI, 27.0% to 67.8%). Six of 7 patients with acute GVHD grade III-IV died from GVHD, which was the leading cause of death. In particular, a shorter interval from the last administration of MOG to allo-HSCT was associated with more severe GVHD. MOG use before allo-HSCT may decrease the ATLL burden; however, it is associated with an increase in TRM due to severe GVHD. Because MOG is a potent anti-ATLL agent, new treatment protocols should be developed to integrate MOG at suitable doses and timing of administration to minimize unwanted GVHD development.

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Colitis mimicking graft-versus-host disease during treatment with the anti-CCR4 monoclonal antibody, mogamulizumab

Cited by 14 publications

References 23 publications

Effective treatment of mogamulizumab-induced head and neck dermatitis with fluconazole in a patient with peripheral T-Cell lymphoma

Effective treatment of mogamulizumab-induced head and neck dermatitis with fluconazole in a patient with peripheral T-Cell lymphoma

The CCR4/CCL17 axis drives intestinal acute Graft versus Host disease after allogeneic bone marrow transplantation

Mogamulizumab Treatment Prior to Allogeneic Hematopoietic Stem Cell Transplantation Induces Severe Acute Graft-versus-Host Disease

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