Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2019 Dec 15;25(24):7272-7274.
doi: 10.1158/1078-0432.CCR-19-2742. Epub 2019 Oct 15.

Mogamulizumab Forecast: Clearer Patients, with a Slight Chance of Immune Mayhem

Cecilia Larocca  1 , Thomas S Kupper  2 , Nicole R LeBoeuf  1
Affiliations
Comment

Mogamulizumab Forecast: Clearer Patients, with a Slight Chance of Immune Mayhem

Cecilia Larocca et al. Clin Cancer Res. .

Abstract

Mogamulizumab, approved by the FDA for relapsed or refractory mycosis fungoides and Sézary syndrome, improves progression-free survival compared with vorinostat in the largest trial to date in cutaneous T-cell lymphoma, with particular efficacy in leukemic disease, but carries a risk of immune-mediated toxicities with concomitant depletion of regulatory T cells.See related article by Kasamon et al., p. 7275.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest/Disclosure statement

Cecilia Larocca has served as a consultant to Kyowa Kirin, Inc. on a medical advisory board meeting.

Figures

Figure 1.
Figure 1.
Effect of Mogamulizumab on T cells and risk for immune-mediated skin toxicity. A) MF T-cells and Tregs exhibit skin homing marker CLA. SS cells, have a TCM phenotype, characterized by CD27. SS cells also express skin homing marker CCR4 and markers L Selectin and CCR7, which allow for recirculation between blood and lymph nodes. Tregs are present in skin and blood and suppress cytotoxic T-cells (TC). Their effect on malignant T-cells is less well understood. B) Mogamulizumab binds to CCR4 and is enhanced to potentiate NK cell ADCC. C) Mogamulizumab clears leukemic disease more effectively than skin disease. Depletion of Tregs by mogamulizumab removes the breaks on cytotoxic T cells, and may result in immune-mediated toxicities, most commonly in the skin (e.g. drug eruption).
See this image and copyright information in PMC

Comment on

References

    1. Kasamon YL, Chen H, de Claro RA, Nie L, Ye J, Blumenthal GM, et al. FDA Approval Summary: Mogamulizumab-kpkc for Mycosis Fungoides and Sezary Syndrome. Clin Cancer Res 2019. doi 10.1158/1078-0432.CCR-19-2030. - DOI - PubMed
    1. Kim YH, Bagot M, Pinter-Brown L, Rook AH, Porcu P, Horwitz SM, et al. Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial. Lancet Oncol 2018;19(9):1192–204 doi 10.1016/S1470-2045(18)30379-6. - DOI - PubMed
    1. Ni X, Jorgensen JL, Goswami M, Challagundla P, Decker WK, Kim YH, et al. Reduction of regulatory T cells by Mogamulizumab, a defucosylated anti-CC chemokine receptor 4 antibody, in patients with aggressive/refractory mycosis fungoides and Sezary syndrome. Clin Cancer Res 2015;21(2):274–85 doi 10.1158/1078-0432.CCR-14-0830. - DOI - PubMed
    1. Hirahara K, Liu L, Clark RA, Yamanaka K, Fuhlbrigge RC, Kupper TS. The majority of human peripheral blood CD4+CD25highFoxp3+ regulatory T cells bear functional skin-homing receptors. J Immunol 2006;177(7):4488–94 doi 10.4049/jimmunol.177.7.4488. - DOI - PubMed
    1. Duvic M, Pinter-Brown L, Foss F, Sokol L, Jorgensen J, Ni X, et al. Correlation of Target Molecule Expression and Overall Response in Refractory Cutaneous T-Cell Lymphoma Patients Dosed with Mogamulizumab (KW-0761), a Monoclonal Antibody Directed Against CC Chemokine Receptor Type 4 (CCR4). Blood 2012;120(21):3697.

Substances