Safety and Efficacy of Mogamulizumab in Patients With Adult T‐cell Leukemia‐lymphoma in Japan: Interim Results of Postmarketing All‐case Surveillance

Abstract

that is uniquely farnesylated. Tipifarnib has been shown to be well tolerated and to have a 41% response rate (7 responses out of 17 patients) in patients (pts) with T-cell non-Hodgkin Lymphoma, including 4 objective responses in 8 pts with peripheral T-cell lymphoma (PTCL) (Witzig et al., 2011). Building on this prior experience, we report herein the preliminary efficacy, safety, and biomarker data from our ongoing Phase 2 study in PTCL.Methods: This Phase 2 study is a multi-institutional, single-arm, openlabel, two-stage (11 + 7) study designed to determine the efficacy and safety of tipifarnib in pts with relapsed/refractory (R/R) PTCL. Pts with R/R PTCL after prior cytotoxic systemic therapy, aged ≥18 years old, and with a performance status of 0-2 were eligible. The primary endpoint of the study is overall response rate. Based on activity observed in the first 18 pts in the study, the protocol has been amended and enrollment is ongoing to an expansion cohort in AITL (N = 12). Enrolled pts are treated with tipifarnib 600 mg administered orally twice daily on days 1-7 and 15-21 of 28-day treatment cycles until progression of disease or unacceptable toxicity. Clinical trial information: NCT02464228. Conclusions: Although this study is ongoing, these preliminary data indicate that tipifarnib is generally well tolerated and has antitumor activity, particularly in pts with AITL histology, absence of 3'UTR CXCL12 SNV, and high levels of CXCL12 gene expression.

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

“…The safety profile reported in this surveillance study was similar to that reported in our preliminary report 12 and in previous clinical trials. 10,11,15 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.…”

“…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. 12 However, it should be paid attention to be led by a small number of patients who have many background factors. According to our multivariate analysis, poor PS of 2-4, low serum albumin <3.5 g/dL, high corrected serum calcium ≥2.75 mmol/L, and high LDH >240 IU/L were associated with poor prognosis, with P < 0.05 or of borderline significance.…”

“…As previously reported, 12 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.…”

“…Survival curves from the first dosing of mogamulizumab estimated by Kaplan-Meier method. (A) Overall survival curve with a median survival of 5.5 mo, (B) Survival curves stratified by ages <70 and ≥70 y with a median survival of 5.5 mo in both populations 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,12 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.…”

“…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, 12 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.…”