<p>Spotlight on Mogamulizumab-Kpkc for Use in Adults with Relapsed or Refractory Mycosis Fungoides or Sézary Syndrome: Efficacy, Safety, and Patient Selection</p>

Abstract

Advanced cutaneous T cell lymphomas (CTCL) including mycosis fungoides (MF) and Sézary syndrome (SS) are often difficult to manage once they become resistant to initial systemic treatment. Current systemic treatments usually provide a limited duration of disease control, leaving this an area in desperate need of new treatment options for better long-term control. These conditions often affect the older population where transplantation may not be a feasible option. Recent studies evaluated a novel CCR4 humanized monoclonal antibody, mogamulizumab, in relapsed/refractory MF and SS, which show a meaningful progression free survival (PFS) benefit. In August 2018, mogamulizumab was approved by the FDA for the treatment of patients with relapsed/refractory MF/SS who have failed at least one treatment. Approval was based on the Phase III MAVORIC study comparing mogamulizumab to vorinostat, an FDA approved drug for this indication, in 372 patients. In this trial, mogamulizumab was found to have a superior PFS with a median of 7.7 months compared to 3.1 months in the vorinostat arm, with a hazard ratio of 0.53, p<0.001. Mogamulizumab was well tolerated with the most common AE being infusion-related reactions (32%), drug rash (20%), diarrhea (23%), and fatigue (22%). We reviewed the literature leading to the development and approval of mogamulizumab and suggest which patients may benefit the most from this treatment.

Chemokine Receptor-Targeted Therapies: Special Case for CCR8

“…Mogamulizumab, a non-fucosylated, humanized antibody specific for human CCR4, is another recent example of an approved antibody reagent causing irAEs in patients with cancer [128,129]. The ADCC-active antibody reagent is approved in the USA and Europe for the treatment of cutaneous T cell lymphomas, including patients suffering from advanced forms of mycosis fungoides or Sezary syndrome, as well as in Japan for advanced adult and peripheral T cell lymphoma [130][131][132]. The distribution of CCR4 + cells is relatively widespread and includes platelets, NK cells, mast cells and T cells [4].…”

Adverse events of monoclonal antibodies use in therapy of hematological malignancies

“…The target of the drug's action is present on the surface of tumor cells in most ATL patients, some patients with other PTCL and CTCL subtypes, but also on the surface of effector T-reg cells, which have the greatest inhibi-Marcela Maksymowicz, Monika Podhorecka, Toxicities of mAbs use in therapy of hematological malignancies tory effect on the anti-tumor immune response. The IRR, major AE of mogamulizumab is thought to be due to a defucosylated Fc region on IgG1, which strongly activates NK cells and causes the release of cytokines and cytotoxic molecules [25,41,42]. Other common toxicities include rash and hematological complications, neutropenia and lymphopenia, considered as an expected effect related to the therapeutic target of mogamulizumab [25,40,42].…”

“…Serious toxicity with mogamulizumab also includes autoimmune AEs, mostly reversible with glucocorticosteroids. The use of mogamulizumab in patients with autoimmune diseases is relatively contraindicated due to the mechanism of action, T-reg cell depletion, and severe grade ≥ 3 AEs previously reported, including immune-related myositis, myocarditis, polymyositis, hepatitis, pneumonitis or Guillain-Barré syndrome [41].…”

CCR4 as a Therapeutic Target for Cancer Immunotherapy

“…The frequent adverse events of mostly grade 1/2 were nausea, chills, headache, and infusion-related reaction [ 154 ]. In a phase 3 randomized study involving 372 patients, Mogamulizumab demonstrated significant improvement in progression-free survival (PFS) and overall response rate (ORR) compared with Vorinostat, a histone deacetylase inhibitor approved for the treatment of CTCLs [ 155 ]: 7.6 months vs. 3.1 months in PFS; 28% vs. 5% in ORR [ 156 , 157 ]. Based on these favorable results, the US Food and Drug Administration (FDA) approved Mogamulizumab in August 2018 for the treatment of adult patients with relapsed or refractory MF or SS after at least one prior systemic therapy [ 156 , 157 ].…”