Role of anti-CCR4 antibody in the treatment of transplant-eligible patients with aggressive adult T-cell leukemia/lymphoma

Abstract

Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell lymphoma caused by the human T-cell lymphotropic virus type I. Patients with aggressive ATL show dismal prognoses, even with intensive dose-dense chemotherapy. Such patients often show chemo-refractoriness. Mogamulizumab (Moga) is a potent treatment option for patients with relapsed or refractory ATL. However, use of Moga before allo-HSCT could theoretically increase the risk of post-transplant complications like graft-versus-host disease (GVHD) as Moga depletes regulatory T-cells (Tregs). We retrospectively assessed the impact of Moga on post-transplant outcomes using data from a nationwide survey. Pre-transplant administration of Moga was associated with an increased risk of grade 3 to 4 acute GVHD and refractoriness to systemic corticosteroid for acute GVHD. The one-year cumulative incidence of non-relapse mortality was significantly higher in patients who were treated with Moga pre-transplant compared with those who were not (43.7% vs. 25.1%, P<0.01). The probability of one-year overall survival was also significantly lower in patients with pre-transplant Moga use compared to those without (32.3% vs. 49.4%, P<0.01). In summary, pre-transplant Moga was significantly associated with an increased risk of GVHD-related mortality, which supports the relevance of CCR4-expressing Tregs after allo-HSCT in humans.