Contributions
Type: Publication Only
Background
Human T-cell leukemia virus type I (HTLV-I) is a human retrovirus that is an etiologic agent of adult T-cell leukemia/lymphoma (ATL/ATLL). The poor outcome of adult ATL is mainly because of an intrinsic resistance of the leukemic cells to conventional or high doses of chemotherapy and severe immunosuppression. 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. MOG has strong antibody-dependent cellular cytotoxicity (ADCC). The common adverse events in the phase II study were infusion reaction and skin rashes. In our study, MOG inhibited the growth of ATL cells and induced remission. CCR4 is expressed not only in ATL cells but also in non-ATL regulatory T cells (Treg). After treatment with MOG, the population of Treg decreased significantly, which boosted the antitumor activity. MOG treatment was associated with the risk of viral infection as an opportunistic infection and skin disturbance (dermopathy).
Aims
In this study, we observed the effects of MOG as CCR4-specific ADCC against CCR4-positive ATL cells. At the same time, frequency of opportunistic viral infection including active CMV infection and severe skin disturbance (dermopathy) have been observed.
Methods
Patients were eligible for enrollment in the study if they were at least 18 years of age, had previously untreated ATL, and recorded a World Health Organization (WHO) performance status (PS) of 0-3. Fourteen patients diagnosed with acute type ATL were selected for this study. In the present study, we treated 14 patients with ATL who were resistant to chemotherapy using MOG monotherapy.
Results
All patients showed CR with a marked decrease in the number of ATL cells. These results suggested that MOG was effective in chemotherapy-resistant ATL patients. No rearrangement of TCRab gene was observed, which indicated molecular CR. Skin disturbance (dermopathy) was found 9 cases of 14 ATL patients treated with MOG monotherapy. The skin rash spread throughout her body with bulla and skin biopsy was performed, and diagnosed as Stevens–Johnson syndrome (SJS)(Figure) in 2 patients of them. Administration of steroid and intravenous immunoglobulin was performed, and SJS gradually improved. Further, in other patients, grade 2 and 3 dermopathy was found, and the patients were treated with glucocorticoid steroid. CMV infection was detected using C7-HRP methods. CMV infection was diagnosed in 5 patients of 14 MOG treated ATL patinets. One of the patients died because of severe CMV infection despite of adequate treatment
Summary
Thus, physicians should be aware of CMV infection and development of immunocompromised condition after MOG monotherapy. In that case, specific anti-CMV treatment for CMV reactivation should be recommended. Moreover, We have to find out the skin rash as soon as possible after treatment with?MOG and it should be recommended quick administration with glucocorticoid. Further study for the dermopathy should be considered.
Keyword(s): ATLL, Chemokine receptor, HTLV-1
Type: Publication Only
Background
Human T-cell leukemia virus type I (HTLV-I) is a human retrovirus that is an etiologic agent of adult T-cell leukemia/lymphoma (ATL/ATLL). The poor outcome of adult ATL is mainly because of an intrinsic resistance of the leukemic cells to conventional or high doses of chemotherapy and severe immunosuppression. 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. MOG has strong antibody-dependent cellular cytotoxicity (ADCC). The common adverse events in the phase II study were infusion reaction and skin rashes. In our study, MOG inhibited the growth of ATL cells and induced remission. CCR4 is expressed not only in ATL cells but also in non-ATL regulatory T cells (Treg). After treatment with MOG, the population of Treg decreased significantly, which boosted the antitumor activity. MOG treatment was associated with the risk of viral infection as an opportunistic infection and skin disturbance (dermopathy).
Aims
In this study, we observed the effects of MOG as CCR4-specific ADCC against CCR4-positive ATL cells. At the same time, frequency of opportunistic viral infection including active CMV infection and severe skin disturbance (dermopathy) have been observed.
Methods
Patients were eligible for enrollment in the study if they were at least 18 years of age, had previously untreated ATL, and recorded a World Health Organization (WHO) performance status (PS) of 0-3. Fourteen patients diagnosed with acute type ATL were selected for this study. In the present study, we treated 14 patients with ATL who were resistant to chemotherapy using MOG monotherapy.
Results
All patients showed CR with a marked decrease in the number of ATL cells. These results suggested that MOG was effective in chemotherapy-resistant ATL patients. No rearrangement of TCRab gene was observed, which indicated molecular CR. Skin disturbance (dermopathy) was found 9 cases of 14 ATL patients treated with MOG monotherapy. The skin rash spread throughout her body with bulla and skin biopsy was performed, and diagnosed as Stevens–Johnson syndrome (SJS)(Figure) in 2 patients of them. Administration of steroid and intravenous immunoglobulin was performed, and SJS gradually improved. Further, in other patients, grade 2 and 3 dermopathy was found, and the patients were treated with glucocorticoid steroid. CMV infection was detected using C7-HRP methods. CMV infection was diagnosed in 5 patients of 14 MOG treated ATL patinets. One of the patients died because of severe CMV infection despite of adequate treatment
Summary
Thus, physicians should be aware of CMV infection and development of immunocompromised condition after MOG monotherapy. In that case, specific anti-CMV treatment for CMV reactivation should be recommended. Moreover, We have to find out the skin rash as soon as possible after treatment with?MOG and it should be recommended quick administration with glucocorticoid. Further study for the dermopathy should be considered.
Keyword(s): ATLL, Chemokine receptor, HTLV-1