医学
蕈样真菌病
内科学
淋巴瘤
人口
分配量
皮肤T细胞淋巴瘤
肿瘤科
成人T细胞白血病/淋巴瘤
免疫学
胃肠病学
药代动力学
T细胞白血病
环境卫生
作者
Mayumi Mukai,Hiroshi Maeda,Kazuya Narushima,Diane R. Mould,Douglas S. Greene
摘要
Abstract Cutaneous T‐cell lymphoma (CTCL) and adult T‐cell leukemia/lymphoma (ATL) are rare non‐Hodgkin lymphomas commonly expressing C‐C chemokine receptor 4 (CCR4). Mogamulizumab is a humanized monoclonal antibody against CCR4 approved in the United States for the treatment of patients with relapsed/refractory mycosis fungoides or Sézary syndrome, the most common forms of CTCL. Pharmacokinetic (PK) and clinical study data from 444 adult patients with ATL or CTCL collected during 6 clinical trials of mogamulizumab were used to construct a population PK model, which was best described by a 2‐compartment model with linear clearance. Albumin, aspartate aminotransferase, mild‐to‐moderate hepatic impairment, and sex were statistically significant predictors of clearance; albumin was also a statistically significant predictor of peripheral volume of distribution; and body surface area was a statistically significant predictor for central volume of distribution. None of the other covariates—for example, age, body weight, body mass index, bilirubin, creatinine clearance, disease type (ATL and CTCL), ATL subtype (acute, lymphoma, and chronic), CTCL subtype (mycosis fungoides and Sézary syndrome), CCR4 expression (status or degree), race (Japanese and non‐Japanese), renal impairment (normal, mild, moderate, and severe), or performance status—had a statistically significant impact. Performance of the final population PK model was acceptable. This model will be valuable for guiding further studies of mogamulizumab.
科研通智能强力驱动
Strongly Powered by AbleSci AI