Use of Mogamulizumab Cautioned in Patients With T-Cell Leukemia and Lymphoma due to Increased Mortality Risk

Adult patients with T-cell lymphoma and leukemia (ATLL) who were treated with mogamulizumab prior to allogeneic hematopoietic cell transplantation (alloHCT) experienced significantly more grade 3/4 graft-versus-host disease (GVHD; 30.9%) compared with patients who did not receive mogamulizumab (17.2%; p<0.01), according to a study published in the Journal of Clinical Oncology.

Shigeo Fuji, MD, of the National Cancer Center Hospital in Tokyo, Japan, and authors assessed 996 patients ≤70 years old with aggressive ATLL who were diagnosed between 2000 and 2013 and who received first-line intensive chemotherapy prior to alloHCT. A total of 82 patients received mogamulizumab a median of 45 days prior to alloHCT.

Treatment with mogamulizumab was associated with higher cumulative incidence of non-relapse mortality at one year (43.7% vs. 25.1%; p<0.01) and lower rates of one-year overall survival (OS; 32.3% vs. 49.4%; p<0.01). In addition, when mogamulizumab was administered within 50 days prior to alloHCT, the one-year OS was lower than when mogamulizumab was administered ≥50 days before alloHCT (20.2% vs. 44.1%; p value not provided).

The authors calculated that treatment with mogamulizumab prior to alloHCT was associated with an 80 percent increased risk of grade 3/4 acute GVHD (relative risk [RR] = 1.80) and twice the risk of becoming refractory to systemic corticosteroids for acute GVHD (RR=2.09; p<0.01).

“The possible mechanism why the interval between mogamulizumab and alloHCT is important should be clarified,” the authors concluded. “When mogamulizumab is administered before alloHCT, it depletes host-derived Tregs at first. When alloHCT 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.”

Source: Fuji S, Inoue Y, Utsunomiya A, et al. Pretransplantation anti-CCR4 antibody mogamulizumab against adult T-cell leukemia/lymphoma is associated with significantly increased risks of severe and corticosteroid-refractory graft-versus-host disease, nonrelapse mortality, and overall mortality. J Clin Oncol. 2016 August 9. [Epub ahead of print]