Association of autoimmunity and long‐term complete remission in patients with Sézary syndrome treated with mogamulizumab

Bonnet, Pierre; Battistella, Maxime; Roelens, Marie; Ram‐Wolff, Caroline; Herms, F.; Frumholtz, L.; Bouaziz, Jean‐David; Brice, Pauline; Bagot, Martine; Masson, Adèle de

doi:10.1111/bjd.17320

Cited by 35 publications

(44 citation statements)

References 8 publications

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“…Mogamulizumab is generally well-tolerated; however some skin-related toxicities due to the induction of autoantibodies recognizing human keratinocytes or melanocytes that induce complement-dependent cytotoxicity have been reported [102]. Of note, targeting CCR4 may also result in the depletion of nonmalignant Tregs, thus leading to or aggravating autoimmune disorders [103]. In this way, it also increases the risk of graft-versus-host dis-ease following allogeneic bone marrow transplantation [104], which should be therefore delayed by at least 50 days from the administration of the last dose [105].…”

Section: Monoclonal Antibodiesmentioning

confidence: 99%

Pathogenesis and Therapy of Primary Cutaneous T-Cell Lymphoma: Collegium Internationale Allergologicum (CIA) Update 2020

Bobrowicz

Fassnacht

Ignatova

et al. 2020

Int Arch Allergy Immunol

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Cutaneous T-cell lymphoma (CTCL) is a heterogeneous disease group of unknown etiology with a complex immunological background. As CTCL arises from T cells that have a vital role in the antitumor response, their therapy is largely aimed at reversing the immunological mechanisms leading to or manifesting during this malignancy. Early disease stages can be controlled with skin-directed therapy in most CTCL cases. Still, advanced CTCL has a dismal prognosis and warrants systemic therapy. Despite considerable progress in understanding the pathophysiology of the disease and the numerous systemic treatment options available, longterm remission rates with conventional treatments alone are still low. Allogeneic hematopoietic stem cell transplantation is currently the only curative option for advanced CTCL, including mycosis fungoides and Sézary syndrome. The aims of this review is to summarize the recent findings on the immunology of this heterogeneous disease and to present the advances in its clinical management.

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Section: Monoclonal Antibodiesmentioning

confidence: 99%

Pathogenesis and Therapy of Primary Cutaneous T-Cell Lymphoma: Collegium Internationale Allergologicum (CIA) Update 2020

Bobrowicz

Fassnacht

Ignatova

et al. 2020

Int Arch Allergy Immunol

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“…For example, mogamulizumab is a humanized anti-CCR4 monoclonal antibody that has shown to increase PFS compared to vorinostat in advanced CTCL in a phase 3 randomized controlled study [ 34 ]. Long-term remissions and auto-immune side-effects have been associated with the use of mogamulizumab [ 35 ], probably due to the depletion of mature regulatory T-cells. Indeed, CCR4 is expressed on malignant T-cells but also on normal mature regulatory T-cells.…”

Section: Bridging Therapies To Allo-hsctmentioning

confidence: 99%

Allogeneic Hematopoietic Stem Cell Transplantation in Cutaneous T-Cell Lymphomas

Dumont

Latour

Ram‐Wolff

et al. 2020

Cancers

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Cutaneous T-cell lymphomas (CTCLs) are non-Hodgkin lymphomas that develop primarily in the skin. They account for almost 80% of primary cutaneous lymphomas. Epidermotropic CTCLs (mycosis fungoides (MF) and Sézary syndrome (SS)) are the most common form of CTCL. The course of the disease ranges from an indolent clinical behavior in early-stage disease to an aggressive evolution in the advanced stages. Advanced-stage disease is defined by the presence of tumors, erythroderma, or significant blood, nodal or visceral involvement. Advanced-stage disease is characterized by frequent disease relapses, refractory disease, a severely impaired quality of life and reduced overall survival. In the last twenty-five years, allogeneic hematopoietic stem cell transplantation (HSCT) has led to prolonged remissions in advanced CTCL, presumably linked to a graft-versus-lymphoma effect and is thus emerging as a potential cure of the disease. However, the high post-transplant relapse rate and severe morbidity and mortality associated with graft-versus-host disease and infections are important issues. Allogeneic HSCT is thus mostly considered in young patients with no comorbidities and an aggressive, advanced-stage CTCL. Allogeneic HSCT gives the best results in patients with a pre-transplant complete remission of the lymphoma. For this reason, one of the challenges is to define the best time to consider allogeneic HSCT in the disease course. Early identification of patients at high risk for progression is important to identify candidates who may benefit from allogeneic HSCT before their disease becomes treatment-refractory. This review describes the role of allogeneic HSCT in CTCL, summarizes the published data and future perspectives in this area.

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“…[160,161]. By targeting CCR-4 mogamulizumab also eliminates nonmalignant regulatory T cells (Tregs) leading to autoimmune disorders [162] and predisposing to increased risk of graft-vs.-host disease (GVHD) after allogeneic bone marrow transplantation [163,164,165,166]. Therefore, in mogamulizumab-treated patients transplantation should be delayed for at least 50 days from the last dose and a Treg count prior to transplant has been suggested [167].…”

Section: Primary Cutaneous Lymphomasmentioning

confidence: 99%

Monoclonal Antibodies in Dermatooncology—State of the Art and Future Perspectives

Bobrowicz

Zagożdżon

Domagala

et al. 2019

Cancers

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Monoclonal antibodies (mAbs) targeting specific proteins are currently the most popular form of immunotherapy used in the treatment of cancer and other non-malignant diseases. Since the first approval of anti-CD20 mAb rituximab in 1997 for the treatment of B-cell malignancies, the market is continuously booming and the clinically used mAbs have undergone a remarkable evolution. Novel molecular targets are constantly emerging and the development of genetic engineering have facilitated the introduction of modified mAbs with improved safety and increased capabilities to activate the effector mechanisms of the immune system. Next to their remarkable success in hematooncology, mAbs have also an already established role in the treatment of solid malignancies. The recent development of mAbs targeting the immune checkpoints has opened new avenues for the use of this form of immunotherapy, also in the immune-rich milieu of the skin. In this review we aim at presenting a comprehensive view of mAbs’ application in the modern treatment of skin cancer. We present the characteristics and efficacy of mAbs currently used in dermatooncology and summarize the recent clinical trials in the field. We discuss the side effects and strategies for their managing.

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Association of autoimmunity and long‐term complete remission in patients with Sézary syndrome treated with mogamulizumab

Cited by 35 publications

References 8 publications

Pathogenesis and Therapy of Primary Cutaneous T-Cell Lymphoma: Collegium Internationale Allergologicum (CIA) Update 2020

Pathogenesis and Therapy of Primary Cutaneous T-Cell Lymphoma: Collegium Internationale Allergologicum (CIA) Update 2020

Allogeneic Hematopoietic Stem Cell Transplantation in Cutaneous T-Cell Lymphomas

Monoclonal Antibodies in Dermatooncology—State of the Art and Future Perspectives

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