{"title":"Exploratory Analysis of Practical Predictive Indices for the Efficacy of Mogamulizumab in Patients With Aggressive Adult T-Cell Leukemia-Lymphoma","authors":"Yutaka Shimazu, Kenta Murotani, Hiroki Kitabayashi, Yukihiro Nishio","doi":"10.1002/hon.70114","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <p>An exploratory analysis of past clinical trials was conducted to propose a predictive scoring system for the efficacy of mogamulizumab, an anti-CC chemokine receptor 4 (CCR4) antibody, based on easily measurable parameters. Factors affecting progression-free survival (PFS) were investigated using data from three clinical trials (NCT00920790, NCT01626664, and NCT01173887) and one clinical study (UMIN000013294) conducted in patients with relapsed/refractory (R/R) or untreated CCR4-positive aggressive adult T-cell leukemia-lymphoma (ATL) receiving mogamulizumab treatment. Twelve routinely measured clinical parameters and three calculated indices—lymphocyte-to-neutrophil count ratio, platelet-to-lymphocyte count ratio, and lymphocyte-to-monocyte count ratio (LMR)—were selected as variables. Univariate Cox proportional hazards analysis identified albumin level, disease type, lactate dehydrogenase (LDH), monocyte count, neutrophil count, and LMR as relevant factors in R/R ATL patients treated with mogamulizumab monotherapy (<i>p</i> < 0.05). A predictive model constructed from multivariate analysis results stratified the monotherapy group (<i>n</i> = 69) into three subgroups, with scores of 0 (<i>n</i> = 5), 1 (<i>n</i> = 25), and 2 (<i>n</i> = 39), based on LDH (0 for < 265 and 1 for ≥ 265) and LMR (0 for ≥ 3.571 and 1 for < 3.571). Median PFS values were 0.57, 0.46, and 0.07 years for scores 0, 1, and 2, respectively (log-rank test: <i>p</i> = 0.005 for score 0 vs. 2; <i>p</i> < 0.001 for score 1 vs. 2). The simple model combining LDH and LMR may predict PFS in patients with R/R aggressive ATL receiving mogamulizumab treatment. Since LDH and LMR are easily measurable in clinical practice, this model could help predict mogamulizumab efficacy and guide treatment decisions in this patient population.</p>\n </section>\n \n <section>\n \n <p><b>Trial Registration:</b> Registration number: UMIN000049135. Date of registration: October 17, 2022</p>\n </section>\n </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 4","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70114","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hematological Oncology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/hon.70114","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
An exploratory analysis of past clinical trials was conducted to propose a predictive scoring system for the efficacy of mogamulizumab, an anti-CC chemokine receptor 4 (CCR4) antibody, based on easily measurable parameters. Factors affecting progression-free survival (PFS) were investigated using data from three clinical trials (NCT00920790, NCT01626664, and NCT01173887) and one clinical study (UMIN000013294) conducted in patients with relapsed/refractory (R/R) or untreated CCR4-positive aggressive adult T-cell leukemia-lymphoma (ATL) receiving mogamulizumab treatment. Twelve routinely measured clinical parameters and three calculated indices—lymphocyte-to-neutrophil count ratio, platelet-to-lymphocyte count ratio, and lymphocyte-to-monocyte count ratio (LMR)—were selected as variables. Univariate Cox proportional hazards analysis identified albumin level, disease type, lactate dehydrogenase (LDH), monocyte count, neutrophil count, and LMR as relevant factors in R/R ATL patients treated with mogamulizumab monotherapy (p < 0.05). A predictive model constructed from multivariate analysis results stratified the monotherapy group (n = 69) into three subgroups, with scores of 0 (n = 5), 1 (n = 25), and 2 (n = 39), based on LDH (0 for < 265 and 1 for ≥ 265) and LMR (0 for ≥ 3.571 and 1 for < 3.571). Median PFS values were 0.57, 0.46, and 0.07 years for scores 0, 1, and 2, respectively (log-rank test: p = 0.005 for score 0 vs. 2; p < 0.001 for score 1 vs. 2). The simple model combining LDH and LMR may predict PFS in patients with R/R aggressive ATL receiving mogamulizumab treatment. Since LDH and LMR are easily measurable in clinical practice, this model could help predict mogamulizumab efficacy and guide treatment decisions in this patient population.
Trial Registration: Registration number: UMIN000049135. Date of registration: October 17, 2022
期刊介绍:
Hematological Oncology considers for publication articles dealing with experimental and clinical aspects of neoplastic diseases of the hemopoietic and lymphoid systems and relevant related matters. Translational studies applying basic science to clinical issues are particularly welcomed. Manuscripts dealing with the following areas are encouraged:
-Clinical practice and management of hematological neoplasia, including: acute and chronic leukemias, malignant lymphomas, myeloproliferative disorders
-Diagnostic investigations, including imaging and laboratory assays
-Epidemiology, pathology and pathobiology of hematological neoplasia of hematological diseases
-Therapeutic issues including Phase 1, 2 or 3 trials as well as allogeneic and autologous stem cell transplantation studies
-Aspects of the cell biology, molecular biology, molecular genetics and cytogenetics of normal or diseased hematopoeisis and lymphopoiesis, including stem cells and cytokines and other regulatory systems.
Concise, topical review material is welcomed, especially if it makes new concepts and ideas accessible to a wider community. Proposals for review material may be discussed with the Editor-in-Chief. Collections of case material and case reports will be considered only if they have broader scientific or clinical relevance.