<p>Mogamulizumab: a new tool for management of cutaneous T-cell lymphoma</p>

Abstract

Cutaneous T-cell lymphoma (CTCL) poses unique treatment challenges, given its range of presentations and numerous systemic therapy options. These options often lack comparative evidence or are characterized by low response rates and short remission duration in relapsed/refractory disease. The approval of mogamulizumab, a humanized, glycoengineered IgG1κ monoclonal antibody targeting the chemokine receptor type 4 (CCR4) chemokine receptor, brings a novel tool into the spectrum of treatment options for advanced CTCL and adult T-cell leukemia/lymphoma (ATLL). CCR4 is expressed in almost all cases of ATLL, and in a majority of CTCLs, particularly when blood involvement is present. In a Phase III randomized trial, mogamulizumab was associated with 28% overall response rate among patients with relapsed CTCL, median progression-free survival of 7.7 months, and median duration of remission of 14.1 months. Responses are more frequent among patients with Sézary syndrome and within the blood compartment. Common adverse effects include rash and infusion reactions, which are usually low grade. Sentinel reports indicate that exposure to mogamulizumab may result in severe or refractory graft vs host disease after allogeneic bone marrow transplantation, highlighting the need for vigilance and expert management. Further research may establish incremental efficacy of combining mogamulizumab with cytotoxic or immunomodulatory agents in CTCL, ATLL, and possibly other lymphomas and even solid tumors.

Successful treatment of mogamulizumab‐resistant mycosis fungoides with mogamulizumab plus etoposide combined therapy: Investigation of the immunomodulatory effects of etoposide on the tumor microenvironment

“…Since mogamulizumab induces cytotoxicity against CCR4+ lymphoma cells by ADCC in advanced CTCL patients, 1,2 cell‐cell contact of CTCL cells with effector cells must be necessary. Since M2 macrophages are the predominant tumor‐associated macrophages (TAMs) that could be detected in the tumor site of CTCL, 5 we hypothesized that etoposide might also modulate the production of chemokines that could recruit CCR4+ CTCL cells (CCL17, CCL22), as well as effector T cells (CXCL5, CXCL10), monocytes, and neutrophils (CXCL5) from M2 macrophages.…”

Impressive continuous complete response after mogamulizumab in a heavily pre-treated Sézary syndrome patient

“…CCR4 is a receptor detectable in a large group of patients with SS, and it plays a central role in the T-lymphocytes homing and migration to the skin. 4 , 6 , 7 CCR4 is also expressed on T regulatory cells (T-Regs), a subset of lymphocytes involved in immunotolerance. The activity of mogamulizumab against T-Regs is long-lasting, and it can lead to a loss of immunotolerance.…”

“…There are some therapeutic options (alemtuzumab, vorinostat, brentuximab vedotin) but no standard of care. 4 In this setting, patients can benefit from a new therapeutic approach: mogamulizumab, a humanized, glycoengineered IgG1κ monoclonal antibody directed against the chemokine receptor type 4 (CCR4). This drug demonstrated an overall response rate (ORR) of 28% in cutaneous T-cell lymphomas in an international, open-label, randomized, controlled phase 3 trial (MAVORIC, NCT01728805) versus vorinostat, with a peak of 37% in SS.…”

Bispecific human IL2‐CCR4 immunotoxin targets human cutaneous T‐cell lymphoma

“…CCR4 is detectable in almost all of the CTCL cases involving the blood using flow cytometry, and percentages of CCR4‐positive cells range from 31% to 97%. This is significantly higher than among healthy individuals (27%) (Ollila et al , 2019). Recently, we have developed a recombinant anti‐human CCR4 immunotoxin (IT) for targeting CCR4 + tumors and Tregs using a unique diphtheria toxin (DT)‐resistant yeast Pichia pastoris expression system (Wang et al , 2015).…”