peripheral t - cell lymphoma ( ptcl ) represents a small heterogeneous group of non - hodgkin lymphoma ( nhl ) that accounts for ~10% of nhls in western countries and ~25% of nhls in japan ( 1,2 ) . ptcls generally have a poor outcome with shorter long - term survival compared with b - cell lymphomas . for example , the 5-year overall survival for the world health organization ( who ) subtype  ptcl - not otherwise specified ( ptcl - nos ) is 32% . ptcl remains extremely difficult to treat as the majority of subtypes become refractory to even aggressive chemotherapy regimens or relapse , and thus , there is a requirement for novel treatment modalities . mogamulizumab is a humanized immunoglobulin g1 monoclonal antibody that targets cc chemokine receptor 4 ( ccr4 ) . ccr4 is highly expressed by aggressive ptcls , particularly adult t - cell leukemia / lymphoma ( atl ) and cutaneous t - cell lymphomas ( ctcls ) . a phase ii study of mogamulizumab yielded an objective response in 35% of patients and a complete response in 14% , with a median progression - free survival ( pfs ) of 3 months ( 3 ) . to date , however , the efficacy of mogamulizumab in patients who become refractory to chemotherapy following autologous stem cell transplantation ( asct ) has not been investigated . the present study reports a patient with ptcl who became refractory following asct and resistant to a salvage therapy , in whom mogamulizumab showed evident efficacy without severe adverse event ( ae ) . a 49-year - old woman presented with subcutaneous tumors and erythema from face to trunk with cervical lymphadenopathy . from a biopsy of the tumor , the patient was diagnosed with ptcl - nos , clinical stage iiia . the patient received 5 cycles of a regimen containing cyclophosphamide , doxorubicin , vincristine and prednisone , and achieved complete remission ( cr ) . the patient subsequently received an asct using the ranimustine / etoposide / cytarabine / melphalan regimen . following asct , the patient remained in cr for 1 month before the skin lesions worsened without lymphadenopathy . the patient received the rituximab , etoposide , methylprednisolone , cytarabine and cisplatin regimen , as a salvage therapy , but the skin lesions remained refractory . re - biopsy of the skin revealed that it was positive for ccr4 ( fig . the patient received mogamulizumab once a week for 8 weeks by intravenous infusion at 1.0 mg / kg . a grade 1 infusion reaction was observed at the first dose ; however , no other ae was observed . after 5 weeks , the skin lesions had improved , and after 8 weeks the patient achieved cr ( fig . according to the who classification , ptcl is a heterogeneous category of mature t - cell neoplasms . the most common mature t - cell neoplasms are ptcl - nos , angioimmunoblastic t - cell lymphoma anaplastic large - cell lymphoma ( alcl ) ( 4 ) . ptcl remains extremely difficult to treat , as the majority of ptcl subtypes become refractory to even aggressive chemotherapy regimens or relapse , and thus there is a medical requirement for novel treatment modalities . mogamulizumab is the first approved glycol - engineered therapeutic antibody and first approved monoclonal antibody to target ccr4 ( 57 ) . ccr4 is principally expressed on regulatory t cells ( tregs ) and helper t cells where it functions to induce homing of these leukocytes to sites of inflammation . tregs have an essential role in providing and maintaining a favorable environment in which tumors can grow . this ability is highly pertinent as subsets of malignant t cells are believed to function as cd4-positive tregs , overexpressing ccr4 ( 810 ) . a previous study of 169 biopsies demonstrated that ccr4 was expressed in the following ptcl subtypes : alcl anaplastic large cell kinase ( alk)-negative ( 67% ) , ptcl - nos ( 38% ) , angioimmunoblastic t - cell lymphoma ( 35% ) , alcl alk - positive ( 4.2% ) , nasal - type natural killer / t - cell lymphoma ( 3.7% ) . within the ptcl - nos subtype , ccr4-positive patients had a significantly poorer prognosis compared to ccr4-negative patients and multivariate analysis confirmed that ccr4 expression was an independent unfavorable prognostic factor ( 11 ) . the drug was approved in japan for the treatment of patients with relapsed / refractory atl in march 2012 and for the treatment of relapsed / refractory ccr4-positive ptcl and ctcl in march 2014 . i study conducted in patients with relapsed atl and ptcl / ctcl , mogamulizumab was well tolerated at doses of 1.0 mg / kg . the overall response rate ( orr ) in the 16 patients included in this study was 31% ( 12 ) . similarly , a recent phase i / ii multicenter , dose - escalation study of mogamulizumab in relapsed patients with ctcl that was conducted in the united states reported an orr of 36.8% ( 13 ) . a japanese multicenter phase ii study investigating mogamulizumab in patients previously treated with ptcl or ctcl was published in 2014 . in the 37 patients who received mogamulizumab , the orr was 35% , complete response was 14% and median pfs was 3 months ( 3 ) . based on the results of this phase ii study , mogamulizumab was approved for use of refractory / relapsed ptcl in japan . in the japanese phase ii the most common of these were hematological events ( lymphocytopenia , 81% ; leukocytopenia , 43% ; thrombocytopenia , 8% ; neutropenia , 38% ) , followed by skin and subcutaneous tissue disorders ( 51% ) ( 3 ) . the patient in the present study had an infusion reaction , which was observed in 24% of patients in the phase ii study . due to the low frequency of this disease and its endemic features , studies that became the foundation of its approval were conducted on relatively small cohorts ; therefore , there is a requirement for larger multicenter investigations on the use of mogamulizumab to treat ptcl . the present case is of particular interest , as to the best of our knowledge , the use of mogamulizumab has not been described previously in detail in ptcl cases refractory following asct . three patients who were refractory following asct were included in the japanese phase ii study ; however , full details of these cases were not included ( 3 ) . the present case became resistant quickly following asct and remained refractory to a salvage therapy , but mogamulizumab monotherapy was markedly effective . in our experience , mogamulizumab has promising efficacy with relapsed ptcl patients following asct . mogamulizumab is likely to provide new and promising treatment options for patients with ccr4-positive t - cell lymphomas ; however , the precise approach may require refinement . for example , patients may benefit from the use of mogamulizumab in combination with other agents . further studies are required to fully understand the physiological effects of this agent and to determine which subtypes of t - cell lymphoma may receive optimum benefit from this agent .
peripheral t - cell lymphoma ( ptcl ) represents a small heterogeneous group of non - hodgkin lymphoma ( nhl ) that accounts for ~10% of nhls in western countries and ~25% of nhls in japan . 
 the disease remains extremely difficult to treat . 
 therefore , novel treatment modalities are required . 
 mogamulizumab is a humanized immunoglobulin g1 monoclonal antibody that targets cc chemokine receptor 4 . to the best of our knowledge , 
 the efficacy of mogamulizumab in patients who are refractory to conventional chemotherapy following autologous stem cell transplantation has not been investigated previously . 
 the present study reports a patient with ptcl who relapsed following autologous stem cell transplantation and became resistant to salvage chemotherapy , in whom mogamulizumab showed evident efficacy without severe adverse event .