Mogamulizumab Treatment Prior to Allogeneic Hematopoietic Stem Cell Transplantation Induces Severe Acute Graft-versus-Host Disease

Abstract

Mogamulizumab (MOG), a humanized anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, has recently played an important role in the treatment of adult T cell leukemia/lymphoma (ATLL). Because CCR4 is expressed on normal regulatory T cells as well as on ATLL cells, MOG may accelerate graft-versus-host disease (GVHD) by eradicating regulatory T cells in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, there is limited information about its safety and efficacy in patients treated with MOG before allo-HSCT. In the present study, 25 patients with ATLL were treated with MOG before allo-HSCT, after which 18 patients (72%) achieved remission. The overall survival and progression-free survival at 1 year post-transplantation were 20.2% (95% CI, 6.0% to 40.3%) and 15.0% (95% CI, 4.3% to 32.0%), respectively. The cumulative incidence of acute GVHD was 64.0% (95% CI, 40.7% to 80.1%) for grade II-IV and 34.7% (95% CI, 15.8% to 54.4%) for grade III-IV. The cumulative incidence of transplantation-related mortality (TRM) was 49.0% (95% CI, 27.0% to 67.8%). Six of 7 patients with acute GVHD grade III-IV died from GVHD, which was the leading cause of death. In particular, a shorter interval from the last administration of MOG to allo-HSCT was associated with more severe GVHD. MOG use before allo-HSCT may decrease the ATLL burden; however, it is associated with an increase in TRM due to severe GVHD. Because MOG is a potent anti-ATLL agent, new treatment protocols should be developed to integrate MOG at suitable doses and timing of administration to minimize unwanted GVHD development.

Pre- and posttransplant use of mogamulizumab in patients with aggressive adult T-cell leukemia-lymphoma: A statement from key opinion leaders in Japan

“…The Fukuoka BMT group retrospectively compared the clinical outcome of patients who did or did not receive Moga before allo‐HSCT (n = 25 and 105, respectively) . In this cohort, the use of Moga significantly improved the disease status before allo‐HSCT, but the incidence of NRM at 1 year after allo‐HSCT was higher, although not significantly so, in patients who received Moga than in those who did not (49.0% vs 27.9%, P = .06).…”

“…In a retrospective analysis of a database from the Fukuoka BMT group, an interval shorter than 80 days between the last Moga dose and allo‐HSCT was associated with a higher incidence of grade III‐IV acute GVHD than an interval of 80 days or longer …”

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

“…Recently, several groups reported the clinical outcomes of cases that received moga before allo-HSCT. These studies consistently reported that the use of moga before allo-HSCT was associated with an increased risk of severe acute GVHD (43)(44)(45)(46), although a case report showed the successful management of acute GVHD (45). However, these studies were rather small to conduct multivariate analyses to adjust for the other risk factors of acute GVHD and other clinical events.…”

“…Using 50 days as a cut-off, a shorter interval between the last moga administration and allo-HSCT was significantly associated with an increased risk of non-relapse mortality and overall mortality. Sugio et al suggested that an interval of <3 months between the last moga administration and allo-HSCT might be associated with an inferior clinical outcome (46). According to some previous reports, the concentration of moga remains more than 10 μg/mL for weeks even after the last administration of 1.0 mg/kg (25).…”

HLA-haploidentical hematopoietic stem cell transplantation with low-dose thymoglobulin GVHD prophylaxis for an adult T cell leukemia/lymphoma patient treated with pretransplant mogamulizumab

“…Anti-CCR4 monoclonal antibody mogamulizumab (Mog) is the first immunotherapeutic agent targeting ATLL. Since CCR4 is expressed on regulatory T cells (Treg), there is growing concern regarding increased risk of severe and refractory acute graft-versus-host disease (aGVHD) in ATLL patients treated with Mog before allo-HSCT (pretransplant Mog) [3–6]. …”