{"title":"分析利妥昔单抗联合环磷酰胺、多柔比星、长春新碱和泼尼松一线治疗患者两年内疾病进展和组织学转化的风险因素:对 JCOG0203 中晚期滤泡性淋巴瘤患者的 15 年随访","authors":"Takashi Watanabe, Yoshihiro Matsuno, Masashi Wakabayashi, Dai Maruyama, Kazuhito Yamamoto, Nobuko Kubota, Kazuyuki Shimada, Kohsuke Asagoe, Motoko Yamaguchi, Kiyoshi Ando, Michinori Ogura, Junya Kuroda, Youko Suehiro, Kunihiro Tsukasaki, Kensei Tobinai, Hirokazu Nagai","doi":"10.1002/hon.3272","DOIUrl":null,"url":null,"abstract":"<p>Follicular lymphoma (FL) is an indolent lymphoma that becomes aggressive due to histological transformation (HT), leading to reduced survival. Patients with FL have different clinical courses and various treatment options. Some patients exhibit shorter survival and experience disease progression within 24 months of diagnosis/treatment (POD24); the optimal treatment remains an unmet needs. Thus, identifying factors that predict shorter survival is essential to stratify treatment and prolong the survival of patients with FL. To analyze risk factors for POD24 and HT in patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as first-line treatment, we performed this post-hoc analysis of patients with advanced indolent B-cell lymphoma in a randomized clinical trial wherein six cycles of R-CHOP were administered every 2–3 weeks. The primary analysis showed no differences in outcomes, which enabled the analysis of 248 patients with FL, assigned to two arms. All histopathological specimens from the 300 enrolled patients were reviewed by three expert hematopathologists. Multivariable analysis implicated Follicular Lymphoma International Prognostic Index (FLIPI) intermediate (odds ratio [OR] 2.531, 95% confidence interval [CI] 0.676–9.466) and high- (OR 2.236, 95% CI 0.160–31.226) risks, B symptoms (OR 2.091, 95% CI 0.747–5.851), and grade 3A (G3A) (OR 1.833, 95% CI 0.634–5.299) as risk factors for POD24. Furthermore, multivariable analysis through a median follow-up of 15.9 years implicated G3A (OR 2.628, 95% CI 0.806–8.575) and high-risk FLIPI (OR 4.401, 95% CI 0.186–104.377) as risk factors for HT. However, an analysis limited to the first 10 years revealed that the prognostic factors elucidated from the longer-term analysis had a greater impact on HT. G3A and high-risk FLIPI may independently predict POD24 and HT, thereby informing treatment stratification of patients with untreated advanced-stage FL in future trials, particularly to address the unmet needs of patients with POD24.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 3","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3272","citationCount":"0","resultStr":"{\"title\":\"Analyzing the risk factors for disease progression within 2 years and histological transformation in patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone as first-line treatment: A 15-year follow-up of patients with advanced follicular lymphoma in JCOG0203\",\"authors\":\"Takashi Watanabe, Yoshihiro Matsuno, Masashi Wakabayashi, Dai Maruyama, Kazuhito Yamamoto, Nobuko Kubota, Kazuyuki Shimada, Kohsuke Asagoe, Motoko Yamaguchi, Kiyoshi Ando, Michinori Ogura, Junya Kuroda, Youko Suehiro, Kunihiro Tsukasaki, Kensei Tobinai, Hirokazu Nagai\",\"doi\":\"10.1002/hon.3272\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Follicular lymphoma (FL) is an indolent lymphoma that becomes aggressive due to histological transformation (HT), leading to reduced survival. Patients with FL have different clinical courses and various treatment options. Some patients exhibit shorter survival and experience disease progression within 24 months of diagnosis/treatment (POD24); the optimal treatment remains an unmet needs. Thus, identifying factors that predict shorter survival is essential to stratify treatment and prolong the survival of patients with FL. To analyze risk factors for POD24 and HT in patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as first-line treatment, we performed this post-hoc analysis of patients with advanced indolent B-cell lymphoma in a randomized clinical trial wherein six cycles of R-CHOP were administered every 2–3 weeks. The primary analysis showed no differences in outcomes, which enabled the analysis of 248 patients with FL, assigned to two arms. All histopathological specimens from the 300 enrolled patients were reviewed by three expert hematopathologists. Multivariable analysis implicated Follicular Lymphoma International Prognostic Index (FLIPI) intermediate (odds ratio [OR] 2.531, 95% confidence interval [CI] 0.676–9.466) and high- (OR 2.236, 95% CI 0.160–31.226) risks, B symptoms (OR 2.091, 95% CI 0.747–5.851), and grade 3A (G3A) (OR 1.833, 95% CI 0.634–5.299) as risk factors for POD24. Furthermore, multivariable analysis through a median follow-up of 15.9 years implicated G3A (OR 2.628, 95% CI 0.806–8.575) and high-risk FLIPI (OR 4.401, 95% CI 0.186–104.377) as risk factors for HT. However, an analysis limited to the first 10 years revealed that the prognostic factors elucidated from the longer-term analysis had a greater impact on HT. G3A and high-risk FLIPI may independently predict POD24 and HT, thereby informing treatment stratification of patients with untreated advanced-stage FL in future trials, particularly to address the unmet needs of patients with POD24.</p>\",\"PeriodicalId\":12882,\"journal\":{\"name\":\"Hematological Oncology\",\"volume\":\"42 3\",\"pages\":\"\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-04-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3272\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Hematological Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/hon.3272\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hematological Oncology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/hon.3272","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
摘要
滤泡性淋巴瘤(FL)是一种惰性淋巴瘤,由于组织学转化(HT)而变得具有侵袭性,导致生存率降低。FL患者的临床病程和治疗方案各不相同。一些患者的生存期较短,并在诊断/治疗后 24 个月内(POD24)出现疾病进展;最佳治疗方法仍是一个未满足的需求。因此,确定预测生存期缩短的因素对于分层治疗和延长 FL 患者的生存期至关重要。为了分析利妥昔单抗加环磷酰胺、多柔比星、长春新碱和泼尼松(R-CHOP)一线治疗患者POD24和HT的风险因素,我们对一项随机临床试验中的晚期惰性B细胞淋巴瘤患者进行了这项事后分析,该试验每2-3周进行6个周期的R-CHOP治疗。主要分析结果显示疗效无差异,因此我们对分配到两组的248名FL患者进行了分析。300 名入选患者的所有组织病理学标本均由三位血液病理学专家进行了审查。多变量分析显示,滤泡性淋巴瘤国际预后指数(FLIPI)中级(几率比[OR] 2.531,95% 置信区间[CI] 0.676-9.466)和高级(OR 2.236,95% CI 0.160-31.226)风险、B 症状(OR 2.091,95% CI 0.747-5.851)和 3A 级(G3A)(OR 1.833,95% CI 0.634-5.299)是 POD24 的风险因素。此外,中位随访 15.9 年的多变量分析显示,G3A(OR 2.628,95% CI 0.806-8.575)和高风险 FLIPI(OR 4.401,95% CI 0.186-104.377)是 HT 的风险因素。然而,仅限于前10年的分析显示,长期分析中阐明的预后因素对高血压的影响更大。G3A和高风险FLIPI可独立预测POD24和HT,从而在未来的试验中为未经治疗的晚期FL患者的治疗分层提供信息,特别是为了满足POD24患者尚未得到满足的需求。
Analyzing the risk factors for disease progression within 2 years and histological transformation in patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone as first-line treatment: A 15-year follow-up of patients with advanced follicular lymphoma in JCOG0203
Follicular lymphoma (FL) is an indolent lymphoma that becomes aggressive due to histological transformation (HT), leading to reduced survival. Patients with FL have different clinical courses and various treatment options. Some patients exhibit shorter survival and experience disease progression within 24 months of diagnosis/treatment (POD24); the optimal treatment remains an unmet needs. Thus, identifying factors that predict shorter survival is essential to stratify treatment and prolong the survival of patients with FL. To analyze risk factors for POD24 and HT in patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as first-line treatment, we performed this post-hoc analysis of patients with advanced indolent B-cell lymphoma in a randomized clinical trial wherein six cycles of R-CHOP were administered every 2–3 weeks. The primary analysis showed no differences in outcomes, which enabled the analysis of 248 patients with FL, assigned to two arms. All histopathological specimens from the 300 enrolled patients were reviewed by three expert hematopathologists. Multivariable analysis implicated Follicular Lymphoma International Prognostic Index (FLIPI) intermediate (odds ratio [OR] 2.531, 95% confidence interval [CI] 0.676–9.466) and high- (OR 2.236, 95% CI 0.160–31.226) risks, B symptoms (OR 2.091, 95% CI 0.747–5.851), and grade 3A (G3A) (OR 1.833, 95% CI 0.634–5.299) as risk factors for POD24. Furthermore, multivariable analysis through a median follow-up of 15.9 years implicated G3A (OR 2.628, 95% CI 0.806–8.575) and high-risk FLIPI (OR 4.401, 95% CI 0.186–104.377) as risk factors for HT. However, an analysis limited to the first 10 years revealed that the prognostic factors elucidated from the longer-term analysis had a greater impact on HT. G3A and high-risk FLIPI may independently predict POD24 and HT, thereby informing treatment stratification of patients with untreated advanced-stage FL in future trials, particularly to address the unmet needs of patients with POD24.
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.