Safety and efficacy of mogamulizumab in patients with adult T-cell leukemia–lymphoma in Japan: interim results of postmarketing all-case surveillance

Abstract

We present the interim results of a postmarketing all-case surveillance study in patients with C-C chemokine receptor 4 (CCR4)-positive, relapsed or refractory adult T-cell leukemia-lymphoma (ATL) treated with the anti-CCR4 monoclonal antibody mogamulizumab since its 2012 launch in Japan. The safety and efficacy analysis populations comprised 484 and 442 patients, respectively. The ATL subtype was acute in 58.9% and lymphoma in 34.2% of patients. All patients were scheduled to receive intravenous infusions of mogamulizumab (1.0 mg/kg) once weekly for eight weeks, alone or in combination with other modalities. Adverse drug reactions (ADRs) were reported in 74.0% of patients, of which 35.7% were serious and 6.2% were fatal. The priority survey items of infusion-related reaction, skin disorder, infection, immune disorder, and tumor lysis syndrome were reported in 29.3, 34.3, 22.1, 3.5, and 2.5% of patients, respectively. Graft-versus-host disease was reported in 25/42 patients who received mogamulizumab before allogeneic hematopoietic stem cell transplantation. The best overall response rate was 57.7% overall, 57.5% in patients treated with mogamulizumab alone, and 58.2% in patients treated with combination therapy. This surveillance indicates that mogamulizumab shows acceptable tolerability in practice; however, because of the risk of serious/fatal ADRs, patients administered mogamulizumab should be carefully monitored.

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

“…In fact, we observed that 7 patients died of GVHD among 49 patients who received mogamulizumab before allogeneic HSCT. Our previous result had demonstrated that the rate of grade III‐IV acute GVHD was 28.6% and might be higher compared with that of HSCT not preceded by mogamulizumab, suggesting the risk of severe GVHD is increased by administering mogamulizumab before allogeneic HSCT in patients with ATL . However, it should be paid attention to be led by a small number of patients who have many background factors.…”

“…The safety profile reported in this surveillance study was similar to that reported in our preliminary report and in previous clinical trials . IRRs, skin disorders, and infections which were collected as mandatory items were the most common ADRs, and the frequencies for the first two events were less than those reported in the clinical study of patients with relapsed ATL using the same administration schedule of mogamulizumab as used in this surveillance .…”

“…An exploratory analysis to determine factors inducing skin disorders was performed for various backgrounds, and body mass index, ATL subtype, PS, concomitant use of non‐anticancer products, and the number of mogamulizumab infusion were statistically associated with the incidence of skin disorders (data not shown). However, except for the number of mogamulizumab infusion described in the previous report, the other factors were not reliable predictors of skin disorders. Skin disorders were late‐onset toxicities with a median time to onset of 35.5 days and a maximum time to onset of 230 days.…”

“…As previously reported, due to the nature of surveillance, data collection for safety was considered to be less frequent and response assessment less objective since they were assessed by an attending physician during clinical practice. Additionally, our observation period, at the longest of 31 weeks from the first dosing of mogamulizumab, might not be sufficiently long to evaluate OS and analyze prognostic factors even though the events occurred in 55% of patients during this period.…”

“…The surveillance was mandated by the Pharmaceuticals and Medical Devices Agency in Japan, and data were collected prospectively from all patients who started mogamulizumab therapy during 1‐year period after the launch. Preliminary safety information from the surveillance has been published in a previous report, and the surveillance was completed in 2018, enrolling more than 500 patients with r/r ATL who were treated with mogamulizumab. Here, we report response rates, survival, and prognostic factors results from the postmarketing surveillance, together with the subset data of elderly patients with ATL in addition to updated safety information.…”