Safety and efficacy of bexarotene for Japanese patients with cutaneous T‐cell lymphoma: Real‐world experience from post‐marketing surveillance

Abstract

To establish real‐world evidence about the safety and efficacy of bexarotene for Japanese patients with cutaneous T‐cell lymphoma, we conducted a nationwide cohort study using data from post‐marketing surveillance for bexarotene treatment. In total, 294 patients with cutaneous T‐cell lymphoma were identified between June 2016 and June 2018. Of these, 267 patients were included as the safety analysis set. Of the 267 patients, 175 were included in the efficacy analysis set. Of these, 139 patients had mycosis fungoides, including 46 with early stage disease and 93 with advanced stage disease. Among the 139 patients with mycosis fungoides, the objective response rate was 46.8%. A significant difference in objective response rate was detected between patients who started with bexarotene at 300 mg/m2 (61.6%) and patients who started with bexarotene at less than 300 mg/m2 (22.6%, p < 0.001). Of the 139 patients with mycosis fungoides, 92 were treated with a combination of bexarotene plus photo(chemo)therapy. A significant difference in objective response rate was seen between bexarotene with a combination of photo(chemo)therapy (57.6%) and bexarotene without a combination of photo(chemo)therapy (25.5%, p < 0.001). Starting bexarotene at 300 mg/m2 and combination with photo(chemo)therapy were detected as independent factors influencing response. Common treatment‐related adverse events included hypothyroidism (85.8%), hypertriglyceridemia (68.5%), hypercholesterolemia (43.8%), and neutropenia (21.3%). Hypertriglyceridemia, hypercholesterolemia, and neutropenia occurred more frequently in patients who started with bexarotene at 300 mg/m2 than patients who started with bexarotene at less than 300 mg/m2 (hypertriglyceridemia, 76.4% vs. 57.0%, p = 0.001; hypercholesterolemia, 49.0% vs. 36.4%, p = 0.045; neutropenia, 28.0% vs. 12.1%, p = 0.002; respectively). The present study indicates that starting bexarotene at 300 mg/m2 and combination of photo(chemo)therapy offer a promising efficacy for the treatment of patients with mycosis fungoides. Efficacy of low‐dose bexarotene plus photo(chemo)therapy should be evaluated in future.

Impact of body mass index on the severity of bexarotene‐associated hypertriglyceridemia: A post hoc analysis of an open‐labeled clinical study of combined bexarotene and phototherapy in Japanese patients with cutaneous T‐cell lymphoma

“…Our data indicated no difference in the incidence of overall hypertriglyceridemia between the two groups stratified by BMI category. This tendency was consistent with the findings from post‐marketing surveillance 10 . Interestingly, however, our data in this study shows that the occurrence of grade ≥3 hypertriglyceridemia was increased in overweight and obese patients as compared with normal and underweight patients.…”

“…However, due to adverse effects of bexarotene treatment, patients on bexarotene require careful monitoring for lipid, thyroid, liver, blood count, creatine kinase, glucose, and amylase abnormalities 6–9 . Among the adverse effects of bexarotene, hypertriglyceridemia is clinically problematic 6–10 . Despite lifestyle management and prophylactic use of lipid‐lowering agents, hypertriglyceridemia is often unavoidable in patients on bexarotene 9 .…”

“…Cabello et al 11 reported that genetic polymorphisms in the genes encoding apolipoprotein A5 (APOA5) and APOC3, which are associated with triglyceride (TG) levels in the general population, are associated with severe bexarotene‐associated hypertriglyceridemia. Screening for APOA5 and APOC3 genotypes might be useful for predicting bexarotene‐associated hypertriglyceridemia, but the predictive sensitivity of these polymorphisms remains unclear 10 …”

Quantitative Analysis of Immune-Reactive Cells among Leukocytes Is Useful for the Diagnosis of Drug Eruptions Caused by Bexarotene

“…Although flow cytometers are widely used for diagnosing CTCL subtypes, they are difficult to use if the number of infiltrating cells is limited, such as the early stage of MF and drug eruptions. Digital microscopic analysis is useful for quantitative analysis of immunohistochemical staining, especially to identify the profiles of lymphocytes such as TILs [9, 10]. For example, we previously evaluated TILs in metastatic melanoma, the profile of which is dramatically changed by the administration of nivolumab plus ipilimumab combined therapy [10].…”

“…Digital microscopic analysis is useful for quantitative analysis of immunohistochemical staining, especially to identify the profiles of lymphocytes such as TILs [9, 10]. For example, we previously evaluated TILs in metastatic melanoma, the profile of which is dramatically changed by the administration of nivolumab plus ipilimumab combined therapy [10]. These reports suggested that digital microscopic analysis is even useful for the analysis of profiles of CTCL instead of flow cytometry.…”