Mogamulizumab for adult T-cell leukemia/lymphoma: a literature review.

BACKGROUND AND OBJECTIVE: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive T-cell malignancy secondary to human T-cell leukemia virus type 1 (HTLV-1) infection. Due to its rapid disease progression and resistance to conventional treatment, the outcome of ATLL remains poor. Approximately 25% of ATLL patients harbor a gain-of-function mutation in the C-C chemokine receptor 4 (CCR4). Mogamulizumab, a humanized anti-CCR4 monoclonal IgG antibody, has emerged as a novel treatment option for both newly diagnosed ATLL and relapsed/refractory ATLL. Despite the presence of several clinical trials and retrospective analyses addressing the combination of mogamulizumab with chemotherapy, there is no clear understanding of the totality of the evidence in this space. We sought to review the literature published on this topic.

METHODS: In this literature review, we retrospectively analyzed clinical trials and retrospective analysis to further evaluate the clinical efficacy of mogamulizumab, its impact on survival outcomes, and the associated toxicity profile in ATLL patients.

KEY CONTENT AND FINDINGS: Our findings suggest that mogamulizumab may offer clinical benefit in ATLL patients in both frontline and relapsed/refractory settings. Combination approaches may further enhance the depth of response. Gain-of-function CCR4 mutations and mogamulizumab-associated cutaneous adverse events have been correlated with improved survival outcomes. However, clinicians should be aware of potential adverse effects, including infusion-related reactions, rashes, infections, as well as the increased risk of steroids-refractory acute graft-versus-host disease (GVHD), when mogamulizumab is used before allogeneic stem cell transplant (allo-SCT).

CONCLUSIONS: Larger, prospective, randomized trials are needed to validate the current findings.