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Objective To elucidate the clinical impact of humanized CCR4 antibody (mogamulizumab) on adult T-cell leukemia-lymphoma (ATL), we retrospectively analyzed the clinical and pathological features and treatment outcomes of aggressive ATL. Methods Twenty-two patients (median age: 65 years) with aggressive ATL [acute- (n=16) or lymphoma-type (n=6)] had their characteristics analyzed. All cases were treated with mogamulizumab at our institution from 2012 to 2018. In addition, we subjected 14 specimens of ATL to histological, immunological, and genetic analyses. Results Regarding the patient outcomes, the overall response rates were 68.1% and 31.8% after 4 and 8 courses (or after the final courses), respectively. The median overall survival (OS) was 95.5 days, while the OS rates at 6 and 12 months were 31.5% and 21.1%, respectively. Concerning patient pathological characteristics, 6 of the 14 patients examined (42.9%) had CCR4 mutations. Regarding the clinicopathological findings related to the mogamulizumab response, notably, the cases with somatic CCR4 mutation tended to have a poorer response (16.7%) than those with wild-type CCR4 (62.5%) after 4 cycles of mogamulizumab. Furthermore, the CCR4 global score tended to be higher in the responder cases than in the non-responder cases. Conclusion The present findings suggest that the CCR4 expression may be related to the mogamulizumab response, although no other significant predictive markers were identified in this study. Further studies will be needed in order to identify more markers related to the mogamulizumab response.
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http://dx.doi.org/10.2169/internalmedicine.2513-18 | DOI Listing |
J Clin Exp Hematop
August 2025
Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.
Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-cell leukemia virus-1. Patients diagnosed with aggressive ATL have a poor prognosis. As response duration to conventional multiagent chemotherapy is short, upfront allogeneic hematopoietic cell transplantation (allo-HCT) is recommended.
View Article and Find Full Text PDFLeuk Lymphoma
August 2025
Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Management of advanced stage cutaneous T-cell lymphoma (CTCL) can be challenging due to lack of durable responses to currently available therapies and their side effects and toxicities. Romidepsin, a histone deacetylase inhibitor, and mogamulizumab, an anti-CCR4 monoclonal antibody, have demonstrated some efficacy as monotherapies, however, survival outcomes remain poor. This retrospective study evaluates the effectiveness of sequential romidepsin-mogamulizumab (Romi-Moga) therapy in 18 patients with advanced CTCL.
View Article and Find Full Text PDFExpert Rev Anticancer Ther
July 2025
Hematology and Stem Cell Transplantation, Yale University School of Medicine, New Haven, CT, USA.
Introduction: Mycosis fungoides (MF) and Sézary syndrome (SS) are T cell lymphomas of the skin with prolonged clinical course requiring multiple lines of therapy in a patient's lifetime. The treatment of MF/SS with available agents is complicated by the differential response in skin, lymph nodes, and blood. Advances in understanding the biology of the disease have led to therapies with better efficacy and improvement in quality of life for patients with relapsed and refractory disease.
View Article and Find Full Text PDFRinsho Ketsueki
July 2025
Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University.
Adult T-cell leukemia/lymphoma (ATL) has a very poor prognosis with conventional multidrug chemotherapy. Lenalidomide, an oral anticancer drug classified as an immunomodulator, showed an overall response rate of 46% in a phase II clinical trial in relapsed ATL. The antibody therapy mogamulizumab showed an overall response rate of 50% in a phase II trial of relapsed C-C motif chemokine receptor 4-positive ATL.
View Article and Find Full Text PDFImmunotherapy
June 2025
Department of Dermatology, HELIOS Klinikum Krefeld, Academic Teaching Hospital of the University of Aachen, Krefeld, Germany.
Mogamulizumab is a humanized monoclonal antibody targeting CCR4, a chemokine receptor expressed on T-cells, including malignant cells found in cutaneous T-cell lymphoma (CTCL). CTCL represents a heterogeneous group of skin lymphomas, with Mycosis Fungoides (MF) and Sézary Syndrome (SS) being the most common subtypes. Despite various treatment options, advanced stages of CTCL often present a challenge, with limited long-term therapeutic success.
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