Mogamulizumab, a humanized monoclonal antibody targeting the CCR4 chemokine receptor, has recently been approved for the treatment of cutaneous epidermotropic T lymphomas. Rash has been reported as one of the side effects. We report six original cases of granulomatous mogamulizumab-associated rash on photo exposed areas clinically mimicking disease progression, which poses a challenge for clinicians.

Material and methods

We retrospectively reviewed the patients treated in Saint-Louis hospital with mogamulizumab for mycosis fungoides (MF) or Sezary syndrome (SS) between 2013 and 2021. Six patients presented with a novel granulomatous erythematous rash during treatment. We hereby analyzed their clinical, histological, and molecular characteristics.

Results

Three women and 3 men with a mean age of 52.8 [37- 64] years were included in this study. The diagnoses were made up of 1 erythrodermic MF at stage IIIB and 5 SS at stage IVA, including 2 transformed forms. Patients had received 1.7 treatments on average before mogamulizumab. A complete blood response to mogamulizumab was obtained in all patients with a complete or partial cutaneous response, whereas an infiltrated granulomatous erythematous rash appeared 9.8 [2- 17] months after the initiation of the treatment, predominantly on the photo-exposed areas (cheeks, scalp, and neck).
Ten skin biopsies were performed in total, with a granulomatous aspect with abundant lympho-histiocytes, polynuclear eosinophils, and sometimes giant cells. Spongiosis phenomena in the epidermis (70%), mild lymphocytic exocytosis (20%), and interface dermatitis (10%) were also observed.
Given the pathological aspect and the absence of a beta lymphocyte clone by high-throughput sequencing of T cell receptor genes in the skin, the diagnose of drug reaction was finally made.
The treatment of topical corticosteroids was not sufficient in most (83.3%) cases. For 5 patients, we decided on spacing out treatments every three or four weeks or even discontinuing the treatment. Methotrexate was added in 3 patients with persistent lesions, with a significant clinical improvement.

Discussion

We present 6 patients treated with mogamulizumab for MF / SS, who developed a granulomatous rash with a predilection for the photo-exposed area. The emergence of this rash, which is difficult to distinguish from plaques of MF, was however associated with a good response to the treatment. Recognition of this granulomatous rash during the treatment with mogamulizumab, which appears to be fairly typical, is essential to avoid unintentional discontinuation of mogamulizumab.