{"title":"滤泡性淋巴瘤转化：现实世界分析，包括利妥昔单抗/比单抗的效果","authors":"D. Shpitzer, C. Perry, I. Avivi","doi":"10.1002/hon.70094_226","DOIUrl":null,"url":null,"abstract":"<p><b>Background</b>: Follicular lymphoma (FL) carries a 2–3% annual risk of transformation to aggressive lymphoma. While most studies focus on transformed FL (T-FL) in previously treated patients (pts), limited data exist on transformation without prior therapy. Additionally, the impact of Obinutuzumab (O) versus Rituximab (R) on T-FL risk is not well documented.</p><p><b>Aims</b>: To provide real-world data (RWD) on FL pts with and without prior anti-FL therapy exposure who developed T-FL, investigating risk factors, treatment patterns, and outcomes.</p><p><b>Methods</b>: We retrospectively reviewed electronic medical records of 1145 FL pts, diagnosed between 2010–2023, age ≥ 18 years, and recorded within Maccabi Healthcare Services. T-FL was defined as a subsequent diagnosis of diffuse large B-cell lymphoma (DLCL) without prior DLCL history. We analyzed transformation risk factors, impact of comorbidities, treatment regimens, and overall survival (OS).</p><p><b>Results</b>: Of 1145 FL pts, 9% (<i>n</i> = 104) developed T-FL over a median follow-up of 71 months (m), reflecting a 1.43% annual transformation rate. Median time to transformation was 42 m. No significant differences were found in age (63 vs. 61 years, <i>p</i> = 0.1) or gender (males 48% vs. 47%, <i>p</i> = 0.8) between T-FL and non-T-FL pts. Charlson Comorbidity Index (CCI) was higher in T-FL pts (median 4 vs. 3, <i>p</i> = 0.005).</p><p>Among 103 T-FL cases, 47% (<i>n</i> = 49) were treatment-naïve, and 53% (<i>n</i> = 54) had prior therapy (26 at diagnosis, 28 after watch-and-wait or local radiotherapy). Median treatment lines among treated pts was 1 (range 1–3). First-line regimens included R-CHOP/CVP (33%, <i>n</i> = 213, predominantly CHOP), R-bendamustine (B) (28%, <i>n</i> = 181), R-monotherapy (11%, <i>n</i> = 71), OB (20%, <i>n</i> = 133), and O-CHOP/CVP (9%, <i>n</i> = 57).</p><p>Median time from initiation of first-line therapy to T-FL in previously treated pts was 23 m, with no significant difference between those treated at diagnosis and those initially managed with watch-and-wait (24 vs. 21 m, <i>p</i> = 0.08). Multivariate analysis revealed that O- vs. R-based regimens (HR 0.43, <i>p</i> = 0.025) and maintenance therapy (HR 0.41, <i>p</i> < 0.001) were associated with reduced transformation risk, whereas B-containing regimens were linked to an increased risk of T-FL (HR 1.52, <i>p</i> = 0.017).</p><p>Median OS from FL diagnosis was shorter in T-FL pts (154 m vs. not reached, <i>p</i> < 0.001), with a median OS since T-FL of 125 m. Previously treated T-FL pts had shorter OS than treatment-naïve pts (34.6 m vs. not reached, <i>p</i> = 0.001). Prior anti-FL therapy (HR 2.23, <i>p</i> < 0.001), male gender (HR 1.77, <i>p</i> = 0.006), and older age at transformation (HR 1.03, <i>p</i> = 0.02) were linked to shorter OS.</p><p><b>Conclusions</b>: Our RWD on T-FL demonstrates several key findings: O-based regimens significantly reduce transformation risk in FL; B-containing regimens are associated with increased T-FL incidence, and patients developing T-FL without prior anti-FL therapy have markedly improved OS. These findings highlight the need for tailored strategies to reduce transformation risk and optimize FL outcomes.</p><p><b>Keyword:</b> indolent non-Hodgkin lymphoma</p><p>No potential sources of conflict of interest.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_226","citationCount":"0","resultStr":"{\"title\":\"FOLLICULAR LYMPHOMA TRANSFORMATION: REAL-WORLD ANALYSIS INCLUDING EFFECT OF RITUXIMAB/OBINUTUZUMAB\",\"authors\":\"D. Shpitzer, C. Perry, I. Avivi\",\"doi\":\"10.1002/hon.70094_226\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><b>Background</b>: Follicular lymphoma (FL) carries a 2–3% annual risk of transformation to aggressive lymphoma. While most studies focus on transformed FL (T-FL) in previously treated patients (pts), limited data exist on transformation without prior therapy. Additionally, the impact of Obinutuzumab (O) versus Rituximab (R) on T-FL risk is not well documented.</p><p><b>Aims</b>: To provide real-world data (RWD) on FL pts with and without prior anti-FL therapy exposure who developed T-FL, investigating risk factors, treatment patterns, and outcomes.</p><p><b>Methods</b>: We retrospectively reviewed electronic medical records of 1145 FL pts, diagnosed between 2010–2023, age ≥ 18 years, and recorded within Maccabi Healthcare Services. T-FL was defined as a subsequent diagnosis of diffuse large B-cell lymphoma (DLCL) without prior DLCL history. We analyzed transformation risk factors, impact of comorbidities, treatment regimens, and overall survival (OS).</p><p><b>Results</b>: Of 1145 FL pts, 9% (<i>n</i> = 104) developed T-FL over a median follow-up of 71 months (m), reflecting a 1.43% annual transformation rate. Median time to transformation was 42 m. No significant differences were found in age (63 vs. 61 years, <i>p</i> = 0.1) or gender (males 48% vs. 47%, <i>p</i> = 0.8) between T-FL and non-T-FL pts. Charlson Comorbidity Index (CCI) was higher in T-FL pts (median 4 vs. 3, <i>p</i> = 0.005).</p><p>Among 103 T-FL cases, 47% (<i>n</i> = 49) were treatment-naïve, and 53% (<i>n</i> = 54) had prior therapy (26 at diagnosis, 28 after watch-and-wait or local radiotherapy). Median treatment lines among treated pts was 1 (range 1–3). First-line regimens included R-CHOP/CVP (33%, <i>n</i> = 213, predominantly CHOP), R-bendamustine (B) (28%, <i>n</i> = 181), R-monotherapy (11%, <i>n</i> = 71), OB (20%, <i>n</i> = 133), and O-CHOP/CVP (9%, <i>n</i> = 57).</p><p>Median time from initiation of first-line therapy to T-FL in previously treated pts was 23 m, with no significant difference between those treated at diagnosis and those initially managed with watch-and-wait (24 vs. 21 m, <i>p</i> = 0.08). Multivariate analysis revealed that O- vs. R-based regimens (HR 0.43, <i>p</i> = 0.025) and maintenance therapy (HR 0.41, <i>p</i> < 0.001) were associated with reduced transformation risk, whereas B-containing regimens were linked to an increased risk of T-FL (HR 1.52, <i>p</i> = 0.017).</p><p>Median OS from FL diagnosis was shorter in T-FL pts (154 m vs. not reached, <i>p</i> < 0.001), with a median OS since T-FL of 125 m. Previously treated T-FL pts had shorter OS than treatment-naïve pts (34.6 m vs. not reached, <i>p</i> = 0.001). Prior anti-FL therapy (HR 2.23, <i>p</i> < 0.001), male gender (HR 1.77, <i>p</i> = 0.006), and older age at transformation (HR 1.03, <i>p</i> = 0.02) were linked to shorter OS.</p><p><b>Conclusions</b>: Our RWD on T-FL demonstrates several key findings: O-based regimens significantly reduce transformation risk in FL; B-containing regimens are associated with increased T-FL incidence, and patients developing T-FL without prior anti-FL therapy have markedly improved OS. These findings highlight the need for tailored strategies to reduce transformation risk and optimize FL outcomes.</p><p><b>Keyword:</b> indolent non-Hodgkin lymphoma</p><p>No potential sources of conflict of interest.</p>\",\"PeriodicalId\":12882,\"journal\":{\"name\":\"Hematological Oncology\",\"volume\":\"43 S3\",\"pages\":\"\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2025-06-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_226\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Hematological Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/hon.70094_226\",\"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.70094_226","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
背景：滤泡性淋巴瘤（FL）每年有2-3%的风险转化为侵袭性淋巴瘤。虽然大多数研究集中在先前治疗过的患者（pts）中转化的FL (T-FL)，但没有先前治疗的转化数据有限。此外，Obinutuzumab (O)与利妥昔单抗(R)对T-FL风险的影响没有很好的文献记载。目的：提供有或没有抗FL治疗的FL患者发生T-FL的真实数据（RWD），调查危险因素、治疗模式和结果。方法：我们回顾性回顾了1145例FL患者的电子病历，这些患者在2010-2023年间诊断，年龄≥18岁，并在马卡比医疗服务中心记录。T-FL被定义为没有dcl病史的弥漫性大b细胞淋巴瘤（dcl）。我们分析了转化的危险因素、合并症的影响、治疗方案和总生存期（OS）。结果：在1145名FL患者中，9% （n = 104）在中位随访71个月(m)期间发展为T-FL，反映出1.43%的年转换率。平均转化时间为42 m。T-FL和非T-FL患者在年龄（63岁对61岁，p = 0.1）和性别（男性48%对47%，p = 0.8）方面没有显著差异。T-FL患者的Charlson共病指数（CCI）较高（中位数为4比3，p = 0.005）。103例T-FL病例中，47% （n = 49）为treatment-naïve， 53% （n = 54）有治疗史（26例诊断时，28例观察等待或局部放疗后）。治疗患者的中位治疗线为1（范围1 - 3）。一线方案包括R-CHOP/CVP （33%, n = 213，主要是CHOP）、r -苯达莫司汀（28%,n = 181）、r -单药治疗（11%,n = 71）、OB （20%, n = 133）和O-CHOP/CVP （9%, n = 57）。在之前接受过治疗的患者中，从开始一线治疗到T-FL的中位时间为23 m，在诊断时接受治疗的患者和最初接受观察和等待治疗的患者之间没有显著差异（24 m对21 m， p = 0.08）。多因素分析显示，0 - vs. r -为基础的方案（HR 0.43, p = 0.025）和维持治疗(HR 0.41, p <；0.001)与转化风险降低相关，而含b方案与T-FL风险增加相关（HR 1.52, p = 0.017）。T-FL患者诊断为FL后的中位OS较短（154 m vs.未达到），p <；0.001)， T-FL后的中位OS为125 m。先前治疗过的T-FL患者的OS短于treatment-naïve患者（34.6 m vs.未达到，p = 0.001）。既往抗fl治疗(HR 2.23, p <；0.001)、男性（HR 1.77, p = 0.006）和转化时年龄较大（HR 1.03, p = 0.02）与较短的生存期有关。结论：我们对T-FL的RWD显示了几个关键发现：基于基础的方案显著降低了FL的转化风险；含b方案与T-FL发病率增加相关，未接受过抗fl治疗的T-FL患者的OS明显改善。这些发现强调需要量身定制的策略来降低转化风险并优化FL结果。关键词：惰性非霍奇金淋巴瘤潜在利益冲突来源
FOLLICULAR LYMPHOMA TRANSFORMATION: REAL-WORLD ANALYSIS INCLUDING EFFECT OF RITUXIMAB/OBINUTUZUMAB
Background: Follicular lymphoma (FL) carries a 2–3% annual risk of transformation to aggressive lymphoma. While most studies focus on transformed FL (T-FL) in previously treated patients (pts), limited data exist on transformation without prior therapy. Additionally, the impact of Obinutuzumab (O) versus Rituximab (R) on T-FL risk is not well documented.
Aims: To provide real-world data (RWD) on FL pts with and without prior anti-FL therapy exposure who developed T-FL, investigating risk factors, treatment patterns, and outcomes.
Methods: We retrospectively reviewed electronic medical records of 1145 FL pts, diagnosed between 2010–2023, age ≥ 18 years, and recorded within Maccabi Healthcare Services. T-FL was defined as a subsequent diagnosis of diffuse large B-cell lymphoma (DLCL) without prior DLCL history. We analyzed transformation risk factors, impact of comorbidities, treatment regimens, and overall survival (OS).
Results: Of 1145 FL pts, 9% (n = 104) developed T-FL over a median follow-up of 71 months (m), reflecting a 1.43% annual transformation rate. Median time to transformation was 42 m. No significant differences were found in age (63 vs. 61 years, p = 0.1) or gender (males 48% vs. 47%, p = 0.8) between T-FL and non-T-FL pts. Charlson Comorbidity Index (CCI) was higher in T-FL pts (median 4 vs. 3, p = 0.005).
Among 103 T-FL cases, 47% (n = 49) were treatment-naïve, and 53% (n = 54) had prior therapy (26 at diagnosis, 28 after watch-and-wait or local radiotherapy). Median treatment lines among treated pts was 1 (range 1–3). First-line regimens included R-CHOP/CVP (33%, n = 213, predominantly CHOP), R-bendamustine (B) (28%, n = 181), R-monotherapy (11%, n = 71), OB (20%, n = 133), and O-CHOP/CVP (9%, n = 57).
Median time from initiation of first-line therapy to T-FL in previously treated pts was 23 m, with no significant difference between those treated at diagnosis and those initially managed with watch-and-wait (24 vs. 21 m, p = 0.08). Multivariate analysis revealed that O- vs. R-based regimens (HR 0.43, p = 0.025) and maintenance therapy (HR 0.41, p < 0.001) were associated with reduced transformation risk, whereas B-containing regimens were linked to an increased risk of T-FL (HR 1.52, p = 0.017).
Median OS from FL diagnosis was shorter in T-FL pts (154 m vs. not reached, p < 0.001), with a median OS since T-FL of 125 m. Previously treated T-FL pts had shorter OS than treatment-naïve pts (34.6 m vs. not reached, p = 0.001). Prior anti-FL therapy (HR 2.23, p < 0.001), male gender (HR 1.77, p = 0.006), and older age at transformation (HR 1.03, p = 0.02) were linked to shorter OS.
Conclusions: Our RWD on T-FL demonstrates several key findings: O-based regimens significantly reduce transformation risk in FL; B-containing regimens are associated with increased T-FL incidence, and patients developing T-FL without prior anti-FL therapy have markedly improved OS. These findings highlight the need for tailored strategies to reduce transformation risk and optimize FL outcomes.
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.
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