Mogamulizumab for Adult T-Cell Leukemia/Lymphoma Associated With Increased Mortality

Patients with adult T-cell leukemia/lymphoma (ATLL) treated with the anti-CCR4 monoclonal antibody mogamulizumab prior to undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) were at significantly greater risk for graft-vs-host disease (GVHD)-related mortality, according to the results of a study published in the Journal of Clinical Oncology.

Mogamulizumab was approved as a treatment for ATLL in Japan; however, according to the study, there have been concerns about the drug’s use pretransplantation because of its effects on regulatory T cells (Tregs).

“This study suggests that the use of mogamulizumab before allo-HSCT significantly worsens clinical outcome mainly because of an increased risk of severe/corticosteroid-refractory acute GVHD,” wrote researchers led by Shigeo Fuji, MD, of the National Cancer Center Hospital in Tokyo. “The results strongly support the clinical relevance of Tregs after allo-HSCT in humans, which is consistent with that in animal models. At present, it seems reasonable to pay careful attention to the use of mogamulizumab for patients with ATLL or other diseases who are eligible for allo-HSCT.”

The researchers studied 996 patients aged 70 or younger who underwent allo-HSCT. All patients were diagnosed with ATLL from 2000 to 2013 and received intensive chemotherapy with multiple drugs at first-line therapy. Prior to transplant, 82 patients underwent treatment with mogamulizumab at a median of 45 days from transplant.

At follow-up, patients who took mogamulizumab experienced significantly more grade 3 or 4 GVHD compared with patients who did not receive mogamulizumab (30.9% vs 17.2%; P < .01). In addition, almost three-quarters of patients (73.4%) in the mogamulizumab group required systemic corticosteroids for acute GVHD compared with 59.8% for the no mogamulizumab group (P = .03).

The researchers calculated that pretransplantation mogamulizumab was associated with an 80% increased risk for grade 3 or 4 acute GVHD (relative risk [RR], 1.80) and twice the risk of refractoriness to systemic corticosteroids for acute GVHD (RR, 2.09; P < .01).

The 1-year cumulative incidence of non-relapse mortality was significantly higher in patients who took mogamulizumab; it was 25.1% in the no mogamulizumab group compared with 43.7% in the mogamulizumab group (P < .01). The estimated probability of 1-year overall survival was 49.4% for the no mogamulizumab group compared with 32.3% in the mogamulizumab group (P < .01).

The researchers evaluated the interval of time between mogamulizumab use and transplantation and found that patients with intervals of less than 50 days had a “dismal clinical outcome,” with an estimated 1-year overall survival rate of 20.2% compared with 44.1% in those patients with an interval of 50 days or greater (P < .01).

“The possible mechanism why the interval between mogamulizumab and allo-HSCT is important should be clarified,” the researchers wrote. “When mogamulizumab is administered before allo-HSCT, it depletes host-derived Tregs at first. When allo-HSCT is conducted soon after mogamulizumab is administered, the concentration of mogamulizumab is high enough to deplete donor-derived Tregs as well, which increases the risk of acute GVHD.”