Toxic epidermal necrolysis in adult T cell leukemia/lymphoma treated with mogamulizumab

Abstract

Dear Editor, Herein, we report a case of adult T cell leukemia/lymphoma (ATLL) accompanied by toxic epidermal necrolysis (TEN) due to mogamulizumab, a monoclonal antibody targeting the CC chemokine receptor 4. A 74-year-old female with lymphoma-type ATLL was initially treated with CHOP therapy; however, the disease progressed after four cycles of CHOP. She then underwent salvage combinatory chemotherapy with vindesine, etoposide, carboplatin, prednisolone (PSL) (VECP) in combination with a single-dose administration of mogamulizumab (1 mg/kg/cycle) on the first day of each cycle. The initial dose of mogamulizumab was safely administered with no adverse events (AEs), along with conventional methyl-PSL 40 mg, acetaminophen, and dexchlorpheniramine maleate. Thereafter, mogamulizumab was safely administered until the fourth cycle. On day 4 of the fifth cycle of VECP with mogamulizumab, the patient was affected by high-grade fever over 38°C, followed by a focal skin rash on the extremities. Skin biopsy on the next day revealed the pathologic changes consistent with erythema multiforme (EM), which could be an early lesion of TEN or Stevens-Johnson syndrome (Fig. 1a) [1]. Despite the temporal improvement by topical steroid and oral antihistamine, the patient then reported blisters on her soles and oral mucosal erosions on day 10. Then, the dermatitis composed of erythemas, plaques, vesicles, and blisters expanded systemically over 50 % of the body (Fig. 1b, c); the lips and all fingers became swollen (Fig. 1d, e); and her conjunctiva became eros i v e . We d i ag n o s e d he r a s h a v i n g T E N du e t o mogamulizumab treatment and initiated corticosteroid pulse therapy with methyl-PSL 1 g/day from day 11. While the TEN-associated symptoms did not resolve with methyl-PSL pulse therapy alone, the addition of intravenous immunoglobulin (IVIg) led to the improvement of TEN and reepithelialization was observed after 2 weeks. Although mogamulizumab-incorporated immunochemotherapy induced transient stable disease, the patient eventually died of disease progression 4 months after the initiation of mogamulizumab.Sjs has been reported as a life-threatening mucocutaneous AEs during the use of mogamulizumab [2], while the complication of TEN has been rarely reported. The precise etiology underlying TEN has not been fully clarified. However, the association of the deregulated immune reaction, including the impaired Treg function, reactive drug metabolites, and the interaction between the two have been suggested as being causative for TEN [3][4][5]. Although we have unfortunately no data on Treg during mogamulizumab treatment, the impaired Treg function by mogamulizumab could be one of the causatives for TEN in our case [2]. Only a single case of late-onset TEN with mogamulizumab has been reported by Shiratori et al. [6]. Although the duration from the last dose of mogamulizumab to the onset of TEN was different between the case reported by Shirotani and the present case, the clinical course and necessary treatments were similar...

The diverse landscape of dermatologic toxicities of non‐immune checkpoint inhibitor monoclonal antibody‐based cancer therapy

“…In addition to targeting malignant CCR4 + T‐cells, mogamulizumab depletes CCD4 + regulatory T‐cells in patients with CTCL 292 . Authors have reported several cases of SJS/TEN with mogamulizumab use, with biopsies showing epidermal necrosis, CD8 + perivascular infiltration, and absence of FOXP3 + regulatory T‐cells 191–195 . Similarly, CTCL patients who had phototoxic interface eruptions because of mogamulizumab also had decreased numbers of FOXP3 + cells upon immunohistochemical analysis 137,175 .…”

“…292 Authors have reported several cases of SJS/TEN with mogamulizumab use, with biopsies showing epidermal necrosis, CD8 + perivascular infiltration, and absence of FOXP3 + regulatory T-cells. [191][192][193][194][195] Similarly, CTCL patients who had phototoxic interface eruptions because of mogamulizumab also had decreased numbers of FOXP3 + cells upon immunohistochemical analysis. 137,175 In a patient with erythema multiforme associated with mogamulizumab, immunofluorescence of biopsy specimens showed deposition of skin-directed IgG and IgM auto-antibodies colocalizing with complement factor C1q in the epidermis.…”

Toxic epidermal necrolysis possibly associated with mogamulizumab in a patient with Sézary syndrome

“…2 Skin rashes are one of the most common side effects of mogamulizumab and are usually associated with a good prognosis. [1][2][3][4] Although previous reports have associated mogamulizumab with the development of TEN in patients with ATLL, [5][6][7][8] to our knowledge, there is no reported case of mogamulizumab-associated TEN in SS.…”

Current Pharmacogenetic Perspective on Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

“…Some rare cases are caused by less commonly seen drugs like albuterol (Maggini et al, 2015;Shariff et al, 2017), taurine-containing energy drink (Begolli Gerqari et al, 2016), radiotherapy for cancers (Rouyer et al, 2018;Esaa et al, 2020), fertility treatment (Hashimoto et al, 2019), vaccines (Oda et al, 2017;Chahal et al, 2018;Flora et al, 2018;Su et al, 2020), commercial cannabinoid oil (Yin et al, 2020), herbs (Bonhomme et al, 2017;Lim et al, 2018), teriflunomide (treating multiple sclerosis) (Gerschenfeld et al, 2015), methotrimeprazine (Moubayed et al, 2017), diuretic drug metolazone (Kumar et al, 2016), etoricoxib (Roy et al, 2018), Dalbergia cochinchinensis (a tree) (Yang et al, 2015), etc. Anticancer drugs like protein kinase inhibitors ribociclib (Lopez-Gomez et al, 2019), palbociclib (Karagounis et al, 2018), afatinib (Doesch et al, 2016), and vemurafenib (Arenbergerova et al, 2017), immune checkpoint inhibitors (ICIs) (including cytotoxic T lymphocyte associated antigen-4 [CTLA-4: monoclonal antibody ipilimumab (Dika et al, 2017)], programmed cell death protein [PD-1: monoclonal antibody nivolumab (Nayar et al, 2016;Salati et al, 2018;Dasanu, 2019), pembrolizumab (Lomax et al, 2019)], programmed cell death ligand 1 [PD-L1: monoclonal antibody atezolizumab (Chirasuthat and Chayavichitsilp, 2018)], and CC chemokine receptor 4 targeting antibody mogamulizumab (Tanba et al, 2016) are also reported to cause SJS/TEN. Cancer patients are at a higher risk to develop SJS/TEN not only due to consequence of the nature of neoplastic diseases, but also exposure to a line of anticancer drugs and disruption of immune system.…”