Dermatologic Events Associated with the Anti-CCR4 Antibody Mogamulizumab: Characterization and Management

Musiek, Amy; Rieger, Kerri E.; Bagot, M.; Choi, Jennifer N.; Fisher, David C.; Guitart, Joan; Haun, Paul; Horwitz, Steven M.; Huen, Auris; Kwong, Bernice Y.; Lacouture, Mario E.; Noor, Sarah; Rook, Alain H.; Seminario‐Vidal, Lucia; Vermeer, Maarten H.; Kim, Youn H

doi:10.1007/s13555-021-00624-7

Cited by 23 publications

(49 citation statements)

References 37 publications

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“…The clinical recognition and pathological confirmation of mogamulizumab‐associated rash (MAR) are important to enable differentiation from cutaneous T‐cell lymphoma (CTCL) progression 6,7 . Here, we report a retrospective case series of patients seen at our centres since 2013, who had granulomatous rash mimicking MF on photoexposed skin.…”

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confidence: 99%

“…[2][3][4][5] The clinical recognition and pathological confirmation of mogamulizumab-associated rash (MAR) are important to enable differentiation from cutaneous T-cell lymphoma (CTCL) progression. 6,7 Here, we report a retrospective case series of patients seen at our centres since 2013, who had granulomatous rash mimicking MF on photoexposed skin. The incidence of this type of rash in the total cohort of patients with CTCL treated with mogamulizumab at our centres was 6%, and the incidence of MAR, as previously reported, was 32%.…”

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Head and neck granulomatous rash associated with mogamulizumab mimicking mycosis fungoides

et al. 2022

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definition of publication was publication of results either in peer-reviewed journals or on ClinicalTrials.gov; our secondary definition was publication in peer-reviewed journals. Variables included in our model (Table 1) were determined a priori.Overall, 141 RCTs met our inclusion criteria. Sixteen RCTs (11%), with 4904 participants, were discontinued prematurely. Reasons included business or sponsor decision (n = 7), insufficient patient recruitment (n = 4) and administration or conduct problems (n = 1). Four RCTs did not provide a reason for discontinuation. Unblinded RCTs (vs. RCTs with blinding of any sort) were significantly more likely to be discontinued (OR 16Á7, 95% CI 2Á22-125) (Table 1).In total, 104 RCTs (74%) met our primary definition of publication, including 93 published in peer-reviewed journals. RCTs investigating topical treatments were significantly more likely to result in nonpublication of results in the multivariable analysis using our primary definition of publication (OR 24Á2, 95% CI 1.14-516) (Table 1), as well as our secondary definition of publication (OR 14Á7, 95% CI 1Á17-185). Discontinued RCTs were associated with nonpublication in the univariable analysis, but this association was attenuated when adjusted for additional factors (OR 4Á50, 95% CI 0Á74-27Á4).In this study of phase III RCTs of psoriasis treatments, 11% of the RCTs were discontinued prematurely, a rate lower than reported in other areas of medicine. [2][3][4] Half of the discontinued RCTs did not cite a reason for discontinuation, and for those that did, the lack of semantic standardization for reasons for discontinuation listed on ClinicalTrials.gov leads to ambiguity and predisposes to misinterpretation. Over a quarter of psoriasis RCTs did not publish their results in peer-reviewed journals or on ClinicalTrials.gov, which is consistent with RCTs in other areas of medicine. 2,3 Topical intervention was the only factor significantly associated with increased nonpublication following adjustment for additional variables. A report on ClinicalTrials.gov for Janus kinase inhibitor therapy suggested that the nonpublication of trials for topical interventions may be related to a lack of efficacy, as many were discontinued due to inefficacy or futility. 5 These findings may also be explained by the increased emphasis in the literature on the evolving systemic treatment landscape.Our study limitations include potential inaccuracies or missing data in trial registry entries, although trial data undergo quality control via automated checks and manual review by ClinicalTrials.gov staff. Our statistical analyses were also limited by the small number of events for certain variables, with inadequate statistical power to assess associations thus limiting interpretation of results.The nonpublication of RCTs of psoriasis remains prevalent. Insight into challenges that prevent RCTs from reaching completion is limited by the lack of reporting of reasons for discontinuation on trial registries. Reporting of reasons for discontinuation on t...

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Head and neck granulomatous rash associated with mogamulizumab mimicking mycosis fungoides

et al. 2022

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“…The development of a mogamulizumab-associated rash can occur up to 24% of patients, with a median onset of 15 weeks. 22 In this patient, the event was a progressively extensive, pruritic, lichenoid rash which required oral steroid therapy and treatment suspension until resolution. It is essential to correctly identify and differentiate a mogamulizumab-associated rash from the disease progression to avoid a premature discontinuation of the treatment, also considering that they seem to occur more frequently in responders.…”

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confidence: 90%

“…Treatment based on daily applications of tretinoin lotion was started to reduce sebaceous hyperplasia growth, while mogamulizumab was continued. Mogamulizumab associated rash have been described recently in MF/SS patients: [22][23][24][25][26][27] they are clinically heterogeneous, and currently, four distinct patterns have been reported: folliculotropic MF-like scalp with alopecia, papules and/or plaques, photo-accentuated dermatitis and morbilliform or erythrodermic dermatitis. It has been hypothesized that mogamulizumab associated rashes may be related to a better clinical outcome in analogy to skin rashes associated with epidermal growth factor receptor inhibitors.…”

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Italian Real-Life Experience on the Use of Mogamulizumab in Patients with Cutaneous T-Cell Lymphomas

Caruso¹,

Castellino²,

Dessì³

et al. 2022

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Mycosis fungoides and Sèzary syndrome are the most studied subtypes common cutaneous T-cell lymphomas. The current treatment objective is to improve the clinical manifestations of the disease in the affected areas, to relieve symptoms and to halt disease progression. Patients with early-stage mycosis fungoides are usually managed with skin-directed therapies, whereas patients with resistant or advanced-stage mycosis fungoides or Sèzary syndrome often require systemic drugs. Over the last decade, new drugs have been developed, increasing the breadth of treatment options for cutaneous T-cell lymphomas patients. Mogamulizumab is a first-in-class defucosylated humanized IgG1 κ monoclonal antibody, which exerts its anti-tumour action by selectively binding to C-C chemokine receptor 4 and increasing antibody-dependent cellular cytotoxicity activity against malignant T-cells. Several clinical trials showed that mogamulizumab is able to effectively control the cutaneous T-cell lymphomas in each site (skin, blood, lymph nodes and viscera), improving patients’ symptoms, function and overall quality of life with a manageable safety profile. In this report, we discuss 12 cases of patients with mycosis fungoides or Sèzary syndrome successfully treated with mogamulizumab in real-life clinical practice in Italy.

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“…5 Accordingly, longlasting complete remissions have been associated with autoimmune manifestations in patients with SS treated with MOGA. [6][7][8] Skin rashes are frequent events, [9][10][11][12] associated with long-term remission. 13 Therefore, MOGA may activate antitumour immunity, while leading to autoimmunity.…”

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Mogamulizumab induces long‐term immune restoration and reshapes tumour heterogeneity in Sézary syndrome*

et al. 2022

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Summary Background Mogamulizumab, an anti‐CCR4 monoclonal antibody, has been shown to increase progression‐free survival in cutaneous T‐cell lymphoma. Objectives We hypothesized that besides the targeted depletion of Sézary cells (SCs), mogamulizumab may reshape the immune tumour microenvironment. Methods Both malignant and benign compartments from 26 patients with B2 stage Sézary syndrome before mogamulizumab initiation were prospectively analysed using KIR3DL2 and TCRVβ markers, serological markers and molecular assessments of clonality. Results Prior to mogamulizumab, the benign subset of CD4+ T cells displayed exhausted phenotypes, with an increased gradient in programmed death‐1, TIGIT, DNAM‐1, CD27, CD28 and CD70 expression from age‐matched controls to patients’ benign CD4+ T cells and to SCs. All patients presented SCs with heterogeneous phenotypes, and differential expression of individual markers was found within distinct malignant subsets. Early complete blood response was observed in 17 of 26 patients and was associated with higher baseline CCR4 expression. A drastic decrease in benign T cells and activated regulatory T‐cell counts was observed during the first 4 weeks. Long‐term follow‐up revealed the emergence of an immune restoration involving CD8+ and naive and stem memory CD4+ T cells, with almost complete disappearance of exhausted lymphocytes. Development of resistance or tumour escape to mogamulizumab was associated with the emergence of CCR4− SCs in blood and skin, displaying significant changes in their heterogeneity patterns, and not explained only by mutations within CCR4 coding regions. Conclusions Mogamulizumab likely contributes to the restoration of efficient immunity and reshapes not only the malignant lymphocyte subset but also the benign subset. These results have potential implications for optimal therapeutic sequences and/or combinations. What is already known about this topic? Management of Sézary syndrome (SS) involves successive therapies that participate as cause and consequence in the emergence of resistant clones, on a background of immunodeficiency. We and others have reported the complex and dynamic heterogeneity of Sézary cells (SCs) during disease progression. Mogamulizumab therapy, by targeting the skin‐homing receptor CCR4, mainly expressed by SCs, has been shown to increase progression‐free survival in patients with SS. What does this study add? Using multicolour flow cytometry, we provide quantification of CCR4 and immune checkpoint molecules on malignant SCs and benign CD4+ T cells from patients with SS, separated using KIR3DL2 and TCRVβ expression. Mogamulizumab is not only aimed at eradicating malignant SCs but potentially contributes to the restoration of efficient immunity. Tumour escape is associated with the emergence of CCR4− SCs, not explained only by mutations within CCR4 coding regions.

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Dermatologic Events Associated with the Anti-CCR4 Antibody Mogamulizumab: Characterization and Management

Cited by 23 publications

References 37 publications

Head and neck granulomatous rash associated with mogamulizumab mimicking mycosis fungoides

Head and neck granulomatous rash associated with mogamulizumab mimicking mycosis fungoides

Italian Real-Life Experience on the Use of Mogamulizumab in Patients with Cutaneous T-Cell Lymphomas

Mogamulizumab induces long‐term immune restoration and reshapes tumour heterogeneity in Sézary syndrome*

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