Friend or foe? Mogamulizumab in allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia/lymphoma

Abstract

Adult T-cell leukemia/lymphoma (ATL/ATLL) is a peripheral T-cell neoplasm associated with human T-lymphotropic virus type-1 (HTLV-1). Even the currently most intensive chemotherapy regimen modified LSG15 (mLSG15, VCAP-AMP-VECP) results in a dismal clinical outcome, with a median overall survival of only around 1 year. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) may lead to long-term remission in a proportion of patients with aggressive ATL, the clinical outcome in patients with refractory or relapsed ATL is unsatisfactory. The anti-CCR4 antibody mogamulizumab (moga) has been recently approved for ATL in Japan, and it is effective in a significant proportion of patients with refractory or relapsed ATL. However, there are major concerns about the harmful influences of pretransplant moga on the immune reconstitution after allo-HSCT. Specifically, moga depletes regulatory T cells (Tregs) for at least a few months, which may increase the risk of graft-versus-host disease (GVHD) after allo-HSCT. A recent retrospective study from Japan clearly showed that pretransplant moga increased the risk of severe and steroid-refractory GVHD, which led to increases in non-relapse mortality and overall mortality. To improve the overall clinical outcome in patients with relapsed or refractory ATL, more studies are needed to incorporate moga without increasing adverse effects on the clinical outcome after allo-HSCT. In this review, we aim to provide an updated summary of the research related to moga and allo-HSCT.

Keywords: Mogamulizumab; adult T-cell leukemia/lymphoma (ATL/ATLL); graft-versus-host disease (GVHD); hematopoietic stem cell transplantation; regulatory T cells (Tregs).

Figure 1

Moga depletes not only ATL cells, but also Tregs. Moga depletes ATL cells through ADCC by NK cells, but also depletes Foxp3⁺ Tregs through ADCC. As a result, moga enhances anti-ATL immunity of anti-ATL NK cells and T cells.

Figure 2

Importance of the interval between the administration of moga and allo-HSCT. (A) With a short interval between moga administration and allo-HSCT, the concentration of moga at allo-HSCT might be high, which is sufficient to deplete donor-derived Tregs as well as recipient-derived Tregs; (B) with a long interval between moga administration and allo-HSCT, the concentration of moga at allo-HSCT might be low, which is no longer able to deplete donor-derived Tregs, although moga has depleted recipient-derived Tregs.