A case series of patients with cutaneous t‐cell lymphoma treated with combination mogamulizumab and other therapies after single agent mogamulizumab

Introduction: Mogamulizumab (moga) is an anti-CCR4, monoclonal antibody approved as monotherapy for the treatment of relapsed/refractory mycosis fungoides (MF) and Sezary syndrome (SS). Combination therapies are frequently utilized in cutaneous T-cell lymphoma (CTCL), in part due to the variation in response across blood, nodal, and skin compartments. Little is known about moga in combination with other therapies. Methods: We conducted a single institution retrospective analysis of MF/SS patients who were treated with moga in combination with other systemic therapies, including peginterferon alpha-2a (IFNα), bexarotene, extracorporeal photopheresis (ECP), and oral methotrexate between March 2019 and March 2023. Baseline characteristics and clinical outcomes were recorded and summarized. Responses were assessed by Olsen staging criteria (Olsen et al., 2022). Results: We identified 9 patients treated with moga combination therapy at our institution (Table 1). Six of 7 patients transitioned from mono to combination therapy due to progressive disease or stable disease with uncontrolled symptom burden. Median time to next treatment was 157.5 days (range 42-330) for moga monotherapy. The best response observed in the 8 patients to single agent moga was classified as: 4 (50%) partial responses (PR), 3 (37.5%) stable disease (SD), and 1 (12.5%) progressive disease (PD). We identified a total of 7 different treatment combinations in our 9 patients (6 systemic therapies and 2 skin-directed), which included IFNα (n = 4), bexarotene (2), ECP (2), total skin electron beam radiation (TSEB) (2), narrow band ultraviolet-B therapy (NBUVB) (1), IFNα + ECP (2), and oral methotrexate (1). Multiple patients received more than one combination treatment. Among the combination therapies, the median time to next treatment was 137 days (range 24-224 days) with 2 out of 6 patients having ongoing responses to moga + IFNα +/- ECP. The patient with PR on moga + IFNα received 7 prior therapies. His skin involvement improved from T4 to T1 but significant disease in the blood persisted (B2). He continues moga + IFNα now 846 days later. Conclusions: Mogamulizumab has improved outcomes for MF/SS patients, but global complete responses are rare with the best responses seen in blood. In our series, the addition of IFNα provided clinical benefits to patients with SD or PD on single agent moga. One patient achieved a lengthy partial response despite persistent disease seen in peripheral blood samples. We speculate the combination of moga + IFNα may augment antibody-dependent cellular cytotoxicity thereby improving efficacy of moga. Additionally, combinatorial approaches may improve responses in skin, nodes, and viscera where lower responses are observed to single agent moga. Further investigations of moga combinations are needed. Keywords: Combination Therapies, Cutaneous non-Hodgkin lymphoma No conflicts of interests pertinent to the abstract.