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. 2021 Jun 1;157(6):700-707.
doi: 10.1001/jamadermatol.2021.0877.

Clinical Characterization of Mogamulizumab-Associated Rash During Treatment of Mycosis Fungoides or Sézary Syndrome

Kelsey E Hirotsu  1 , Tatiana M Neal  1 , Michael S Khodadoust  2 , Jennifer Y Wang  1   3 , Kerri E Rieger  1   3 , Jenna Strelo  1 , Eric Hong  1 , Youn H Kim  1   2 , Bernice Y Kwong  1
Affiliations

Clinical Characterization of Mogamulizumab-Associated Rash During Treatment of Mycosis Fungoides or Sézary Syndrome

Kelsey E Hirotsu et al. JAMA Dermatol. .

Abstract

Importance: Mogamulizumab is a monoclonal antibody against CCR4 approved for treatment for mycosis fungoides (MF) and Sézary syndrome (SS). Mogamulizumab-associated rash (MAR) is difficult to differentiate from cutaneous MF or SS, which can lead to unnecessary discontinuation of drug use because of concern for severe drug reaction or incorrect presumption of disease relapse or progression in the skin.

Objective: To examine the most common clinical presentations of MAR in patients with MF or SS and the diagnostic and management challenges.

Design, setting, and participants: This retrospective case series assessed patients from a multidisciplinary cutaneous lymphoma clinic and supportive oncodermatology clinic at a major academic referral center who had a diagnosis of MF or SS and received mogamulizumab from January 1, 2013, to January 1, 2020. Treatment was followed by new or worsening rash with skin biopsy results compatible with drug eruption determined by clinicopathologic correlation and molecular testing to exclude active malignant disease.

Exposures: At least 1 dose of mogamulizumab.

Main outcomes and measures: Mogamulizumab-associated rash was characterized by clinical features, including time to onset, clinical presentation, histopathologic features, and management approach.

Results: The study included 19 patients with MF or SS who developed MAR (median age, 65 years; age range, 38-82 years; 10 [52.6%] male). Median time to MAR onset was 119 days (range, 56 days to 3.8 years). Patients with MAR exhibited 4 predominant clinical presentations: (1) folliculotropic MF-like scalp plaques with alopecia, (2) papules and/or plaques, (3) photoaccentuated dermatitis, and (4) morbilliform or erythrodermic dermatitis. The most common anatomical region involved was the head and neck, including the scalp. Histopathologic findings were variable and did not correspond to primary clinical morphologic findings. Immunohistochemistry and T-cell clonality ancillary testing were helpful to distinguish MAR from disease. Most patients with MAR (14 of 19) discontinued mogamulizumab treatment; however, no life-threatening severe cutaneous adverse drug reactions occurred, and the decision for drug therapy cessation was usually multifactorial. Four patients were treated again with mogamulizumab with no life-threatening drug-related events. Approaches to management of MAR include topical corticosteroids, systemic corticosteroids, and/or methotrexate.

Conclusions and relevance: This case series found that mogamulizumab-associated rash had a heterogeneous clinical presentation with variable and delayed onset in patients with MF or SS. Mogamulizumab-associated rash exhibited a predilection for the head and neck and was difficult to clinically distinguish from relapse or progression of disease. Recognition of the most common clinical presentations can help prevent unnecessary discontinuation of mogamulizumab treatment. The presence of MAR does not necessitate permanent discontinuation of or avoidance of retreatment with mogamulizumab.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Khodadoust reported receiving consultant fees from Kyowa Kirin outside the submitted work. Dr Rieger reported receiving drug advisory board fees and honoraria from Kyowa Kirin outside the submitted work. Dr Kim reported receiving drug advisory board fees from Kyowa Kirin during the conduct of the study and grants from Kyowa Kirin, advisory board fees from Galderma, advisory board fees from Regeneron, advisory board fees from Sanofi, advisory board fees from Mundipharma, grants from Corvus, grants from Innate, grants from Elorac, grants from Trillium, and grants from CRISPR outside the submitted work. Dr Kwong reported receiving personal fees from Oncoderm, Kyowa Kirin, and Genentech during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Clinical Characteristics of Patients With Mogamulizumab-Associated Rash (MAR)
Patients with MAR exhibit 4 predominant clinical presentations, including (1) folliculotropic mycosis fungoides (F-MF)–like plaques with alopecia on the head and neck, including the scalp (A-C); (2) papules and/or plaques, often with lichenoid or psoriasiform features (D); (3) photoaccentuated dermatitis (E); and (4) morbilliform or erythrodermic dermatitis (F).
Figure 2.
Figure 2.. Histopathologic Features of Mogamulizumab-Associated Rash (MAR)
Three major histopathologic reaction patterns of MAR were identified. The most common pattern showed overlapping features of psoriasis and a chronic spongiotic dermatitis (hematoxylin-eosin, original magnification ×20) (A). Other cases showed a lichenoid or interface pattern with dyskeratosis (hematoxylin-eosin, original magnification ×10) (B). A smaller subset of cases had a granulomatous reaction pattern with moderately to well-formed granulomas. Some granulomas were palisading in appearance, reminiscent of granuloma annulare (hematoxylin-eosin, original magnification ×20) (C).
See this image and copyright information in PMC

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