Introduction

Mogamulizumab (moga), an anti-CCR4 monoclonal antibody, is approved in cutaneous T-cell lymphomas (CTCL). Moga immune-related adverse events (IrAE) have been described, and we report the first case series of alopecia areata (AA) following the administration of moga.

Material and method

We retrospectively investigated the occurrence of AA during moga therapy in patients treated for CTCL between jan-2015 and jan-2021. Data were collected by the 31 hospital centers of the French Group for the Study of Cutaneous Lymphomas.

Results

Of 157 patients treated with moga (47 in the MAVORIC trial and 110 in "real life"), 4 developed AA: 3 alopecia totalis and 1 ophiasis. The patients were 3 women and 1 man with a median age of 59 years (35-81), all treated for stage IVA1 Sézary syndrome (SS). They had no history of autoimmunity and no other IrAE. The median time to onset of AA after moga introduction was 12 months (6-16). Upon the occurrence of AA, 2 patients had complete response (CR) of their SS, and 2 had good partial response (PR). Skin biopsies were performed in 2 patients, revealing a peribulbar CD8+ T-cells infiltration with no evidence of a specific localization of SS.

With a median follow-up of 49 months (18-76) since the introduction of moga, the AA was stable in 2 patients, for whom SS was still in CR or PR. In one patient, discontinuation of moga because of the pandemic was followed, 8 months later, by hair regrowth and relapse of SS. Restarting moga resulted in SS complete response with stabilization of the AA in an ophiasis type. Finally, one patient had a recurrence of SS at 18 months, leading to the discontinuation of moga, and her hair grew back completely. This patient is still alive in PR after an allogenic bone marrow transplantation.

Discussion

CCR4 is expressed by Sézary cells and regulatory T-cells (Tregs). In SS, moga depletes CCR4+ Tregs, thus augmenting cytotoxic T-cells anti-tumor immunity. The loss of homeostasis between Tregs and effector T-cells would be at the root of IrAEs.
In patients with alopecia totalis, it has been shown that the level of circulating and perifollicular Tregs is significantly low compared to healthy subjects. Indeed, patients 1 and 2 had very low blood Treg counts (data not available for the others).
The frequency of moga-induced IrAEs is not exactly established. To our knowledge, only one patient with AA has been reported. This patient had a patchy AA, and simultaneously presented 3 other IrAEs (hepatitis, thyroiditis, vitiligo). Patients with long-term CR after the occurrence of moga-induced IrAE have been described, although the relationship between IrAE and moga efficacy warrants further evaluation.

Conclusion

AA can arise without additional moga-induced IrAE. It seems to be associated with a good efficacy of moga, and its evolution seems to be correlated with that of the SS, but its predictive value on the long term has yet to be determined.