None of the other covariates-for example, age, body weight, body mass index, bilirubin, creatinine clearance, disease type (ATL and CTCL), ATL subtype (acute, lymphoma, and chronic), CTCL subtype (mycosis fungoides and Sézary syndrome), CCR4 expression (status or degree), race (Japanese and non-Japanese), renal impairment (normal, mild, moderate, and severe), or performance status-had a statistically significant impact.
This prospective, observational, postmarketing surveillance was conducted to evaluate the safety and effectiveness of mogamulizumab, an anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, in patients with CCR4-positive, relapsed or refractory (r/r) adult T-cell leukemia-lymphoma (ATL) in Japan.
This study suggests that frequencies of CCR4 expression and genomic CCR4 mutations and an association between the two may be considerably different between ATL cases and non-ATL T/NK-cell lymphomas.
The anti-CCR4 mAb, mogamulizumab, offers therapeutic benefit to patients with adult T-cell leukemia-lymphoma (ATL), but skin-related adverse events (AE) such as erythema multiforme occur frequently.
Although the anti-CCR4 antibody mogamulizumab (moga) shows striking antitumor activity against adult T cell leukemia (ATL), it can also cause fatal immunological pathology such as severe skin rash and graft-versus-host disease, which might be attributed to depletion of CCR4<sup>+</sup> regulatory T cells.
Mogamulizumab (Mog) is a defucosylated, therapeutic monoclonal antibody, targeting CCR4 and was first approved in Japan for the treatment of adult T-cell leukaemia/lymphoma (ATLL), followed by cutaneous T-cell lymphoma and peripheral T-cell lymphoma.
The present study sought to elucidate the prognosis of adult T-cell leukemia-lymphoma (ATL) patients receiving mogamulizumab, a defucosylated anti-CCR4 monoclonal antibody.
Areas covered: Mogamulizumab is a humanized, defucosylated monoclonal antibody that acts by targeting the CC chemokine receptor 4 (CCR4) on malignant cells of ATL.
Mogamulizumab, an anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, is one of the promising agents for CCR4-positive T-cell lymphomas, especially for ATL.
Galectin-9 as a Predictive Marker for the Onset of Immune-Related Adverse Effects Associated with Anti-CCR4 MoAb Therapy in Patients with Adult T Cell Leukemia.
Mogamulizumab (Mog), a humanized anti-CC chemokine receptor 4 (CCR4) mAb that mediates antibody-dependent cellular cytotoxicity (ADCC) using FcγR IIIa (CD16)-expressing effector cells, has recently been approved for treatment of CCR4-positive adult T-cell leukemia (ATL) in Japan.
Furthermore, the anti-CCR4 monoclonal antibody mogamulizumab has been shown to have marked cytotoxic effects on ATL cells, especially in the leukemic type of ATL.
Recently, the FDA has approved four drugs for patients with relapsed/refractory PTCL over the past 5 years, and if one counts the recent Japanese approval of the anti-CCR4 monoclonal antibody for patients with adult T-cell leukemia/lymphoma, five drugs have been approved worldwide.
These findings implicate somatic gain-of-function CCR4 mutations in the pathogenesis of ATLL and suggest that inhibition of CCR4 signaling might have therapeutic potential in this refractory malignancy.
Lymphotoxin (LT) β and CCL21 expression was significantly higher and that of CCR10 relatively for MF, while CCR4 and CLA expression was relatively higher for ATLL.
Previously, we have shown that an AP-1 family member, FRA-2, is constitutively expressed in adult T-cell leukemia/lymphoma (ATL) and, together with JUND, upregulates CCR4 and promotes ATL cell growth.
Our results, thus, demonstrate the presence of a common oncogenic cascade initiated by FRA2/JUND in CCR4-expressing mature T-cell malignancies such as ATLL and CTCLs.
The approval was granted April 30, 2012 by the Japanese Ministry of Health, Labour and Welfare for patients with relapsed or refractory CCR4-positive adult T-cell leukemia-lymphoma.
In addition, LBH589 caused a marked decrease in levels of factors involved in ATLL cell proliferation and invasion such as CCR4, IL-2R and HTLV-1 HBZ-SI, a spliced form of the HTLV-1 basic zipper factor HBZ.