Induction of molecular remission by using anti-CC-chemokine receptor 4 (anti-CCR4) antibodies for adult T cell leukemia: a risk of opportunistic infection after treatment with anti-CCR4 antibodies

Abstract

The CC-chemokine receptor 4 (CCR4) is expressed in almost ATLL cells. Thus, anti-CCR4 antibodies can be used as a treatment strategy for ATLL. Mogamulizumab (MOG), which is a defucosylated anti-CCR4 monoclonal antibody, showed good results even in patients with recurrent ATLL in phase I or II studies. We treated 8 elderly patients with ATL who were resistant to chemotherapy using MOG monotherapy. All patients received 1.0 mg/kg of mogamulizumab (MOG) once per week for 8 weeks by intravenous infusion. In the present study, we observed CCR4-specific ADCC against CCR4-positive ATL cells. All patients showed CR with a marked decrease in the number of ATL cells. However, 2 patients contracted viral infection because of severe lymphopenia. One patient died because of severe cytomegalovirus infection despite adequate treatment. One patient had Stevens' Johnson syndrome. These results suggested that MOG was effective in chemotherapy-resistant ATL patients. However, CCR4 is not only on ATL cells but also on endogenous Treg. The decrease in the number of Treg after MOG monotherapy has been expected to boost the antitumor activity and to be involved in the development of immune disorders, including autoimmune diseases. Furthermore, a decrease in CD4+ T cells led to viral infection. In conclusion, several treatments for prophylaxis of opportunistic infection, including CMV infection, should be recommended.

Targeting chemokine receptors in disease – a case study of CCR4

“…The efficacy of mogamulizumab in the treatment of CCR4-negative solid cancers, where Treg depletion is desirable, is currently being assessed. A recent report outlining the treatment of four elderly patients with mogalizumab has also suggested that an additional side-effect may be the risk of opportunistic infection with cytomegalovirus ( Ohyama et al, 2014 ).…”

Development of Epstein-Barr Virus-related Primary Diffuse Large B-cell Lymphoma of the Central Nervous System in a Patient with Peripheral T-cell Lymphoma, Not Otherwise Specified after Mogamulizumab Treatment

“…There have been some reports describing opportunistic viral infection after mogamulizumab therapy for patients with ATL, such as cytomegalovirus infection ( 8 , 9 ), reactivation of hepatitis B virus ( 10 ), and fatal pneumonia and viremia due to parainfluenza virus ( 11 ). Indeed, fatal cytomegalovirus pneumonia after mogamulizumab therapy was reported in a patient with T-cell lymphoma other than ATL ( 12 ).…”

Cytomegalovirus Pneumonia after Anti-CC-chemokine Receptor 4 Monoclonal Antibody (Mogamulizumab) Therapy in an Angioimmunoblastic T-cell Lymphoma Patient

“…Rituximab decreases the number of normal CD20-positive cells (9), while alemtuzumab causes lymphocytotoxic immunosuppression through the suppression of T-cell function and decrease in the number of CD4 cells (10). Ohyama et al described that 2 of 4 patients with ATLL who underwent mogamulizumab therapy developed CMV infection (11). Two patients with CMV infection achieved molecular CR.…”