Safety and effectiveness of mogamulizumab in relapsed or refractory adult T‐cell leukemia‐lymphoma

Abstract

ObjectiveThis prospective, observational, postmarketing surveillance was conducted to evaluate the safety and effectiveness of mogamulizumab, an anti‐CC chemokine receptor 4 (CCR4) monoclonal antibody, in patients with CCR4‐positive, relapsed or refractory (r/r) adult T‐cell leukemia‐lymphoma (ATL) in Japan.MethodAll patients were scheduled to receive intravenous infusions of mogamulizumab 1.0 mg/kg once weekly for 8 weeks, alone or in combination with other modalities.ResultsIn the safety analysis population comprising 572 patients, mogamulizumab therapy was started between May 29, 2012, and April 30, 2013, and adverse drug reactions (ADRs) were reported in 73.4% (38.6% serious cases) of patients. The most common ADRs were skin disorders (33.2% [10.8% serious cases]), infusion‐related reactions (30.1% [4.7% serious cases]), and infections (22.0% [14.7% serious cases]). In the effectiveness analysis population comprising 523 patients, the best overall response rate and the response rate at the end of therapy were 57.9% and 42.0%, respectively. The median overall survival was 5.5 months. Safety and effectiveness results were similar between patients aged ≥70 and <70 years.ConclusionThis postmarketing surveillance confirmed the safety and effectiveness of mogamulizumab for the treatment of patients with r/r ATL, including elderly patients, in clinical practice.

Systematic review of survival outcomes for relapsed or refractory adult T‐cell leukemia‐lymphoma

“…Eight studies included a mogamulizumab treatment arm: five were single‐arm studies, and three were two‐arm studies. One mogamulizumab single‐arm study reported a subgroup analysis of mogamulizumab treatment prior to allo‐HSCT 30 . In each two‐arm study, mogamulizumab treatment was compared with chemotherapy without mogamulizumab.…”

“…Time to salvage therapy from diagnosis of r/r disease was not explicitly reported in any study. Two studies reported the study regimen as the first salvage therapy after r/r diagnosis, 31,35 and another two studies reported the proportion of patients with only one prior regimen (60–82%) 30,36 . However, four studies reported the median time to study regimen initiation from initial diagnosis, which ranged from 6.0 to 25.2 months 26,33,37,38 .…”

“…The median OS varied across studies that included mogamulizumab treatment arms (2.2–17.6 months), mogamulizumab treatment prior to allo‐HSCT arms (4.5–7.4 months), allo‐HSCT arms (3.8–6.2 months), and other chemotherapy arms (4.1–20.3 months) (Figure 2). One study reported in their subgroup analysis that the median OS for patients who received mogamulizumab treatment prior to allo‐HSCT was longer than patients who received mogamulizumab treatment without transplant (7.4 months [95% CI: 5.2–9.9] vs. 5.5 months [95% CI: 4.8–6.4]) 30 . In another study, the OS for mogamulizumab treatment prior to transplantation and the OS for patients who did not receive mogamulizumab treatment prior to their transplantation were similar (4.5 months [95% CI: 1.3‐NA] vs. 4.9 months [95% CI: 3.7–6.7]) 31 …”

“…Similar heterogeneity was found among survival outcomes for allo‐HSCT following mogamulizumab. Ishitsuka et al described slightly longer survival among patients receiving allo‐HSCT following mogamulizumab compared with mogamulizumab alone, although the groups were not directly compared 30 . Another small Japanese study suggested that mogamulizumab may be good as a second‐line salvage therapy in cases of relapse after allo‐HSCT 41 .…”

A review of antibody-based therapeutics targeting G protein-coupled receptors: an update

“…Kyowa Hakko Kirin continues to further evaluate the efficacy of this mAb in other cancer indications, such as other lymphomas and leukemias, gastric cancer, and triple-negative breast cancer (TNBC). Although certain rare autoimmune side effects (usually affecting the skin) have been observed in a number of patients, these are treatable [58] and mogamulizumab is generally considered to be safe and efficacious [59]. A Phase 1 trial assessing mogamulizumab in combination with nivolumab in both advanced and metastatic cancer indicated an acceptable safety profile and efficacy, thus this could present another potential option in cancer therapy [60].…”