Pub Date : 2026-02-01DOI: 10.1016/j.clml.2025.10.021
Adolfo Jesús Sáez-Marín , Gema Hernandez-Ibarbu , Lucia Medina Alba , Reyes Mas Babio , Andrea Tamayo , Ana Cuervo Fonseca , Jose María Sanchez-Pina , Rafael Alberto Alonso-Fernández , Nieves Lopez-Muñoz , Alberto Blanco , Pablo Justo , Noelia Garcia-Barrio , Alberto Tato , Juan Luis Cruz , David Perez-Rey , Ana Jimenez-Ubieto , Javier de la Cruz , María Calbacho , Joaquín Martínez-López
Introduction
The role of autologous hematopoietic stem cell transplantation (auto-HCT) in multiple myeloma (MM) patients over 65 years remains unclear due to their underrepresentation in clinical trials. This study evaluates the safety and efficacy of auto-HCT in this population using real-world data from the TriNetX network.
Methods
A retrospective cohort study was conducted on MM patients treated at Hospital 12 de Octubre (2013-2023). Three cohorts were analyzed: patients > 65 years undergoing auto-HCT (n = 60), ≤ 65 years with auto-HCT (n = 235), and > 65 years without auto-HCT (n = 59). A validation cohort from TriNetX included 5087 patients > 65 and 10,667 ≤ 65 years receiving auto-HCT, along with 54,757 > 65 years without auto-HCT. Primary outcomes included progression-free survival (PFS), time to next treatment (TNT), overall survival (OS), and non-relapse mortality (NRM).
Conclusion
Auto-HCT improved PFS and OS in selected elderly patients. The 6-year PFS was 45.0% (> 65) versus 55.0% (≤ 65) (HR 1.25; P = .365), and the 6-year OS was 57.8% (> 65) versus 81.1% (≤ 65) (HR 2.11; P = .025). TNT rates were similar (64.4% vs. 63.6%; HR 0.93; P < .01). Toxicity and mortality were comparable. These findings support auto-HCT as a valuable consolidation therapy in selected elderly MM patients, emphasizing the need for personalized strategies to optimize outcomes.
导读：自体造血干细胞移植（auto-HCT）在65岁以上多发性骨髓瘤（MM）患者中的作用尚不清楚，因为它们在临床试验中的代表性不足。本研究使用来自TriNetX网络的真实数据评估了auto-HCT在该人群中的安全性和有效性。方法：对2013-2023年10月12日住院治疗的MM患者进行回顾性队列研究。分析了三个队列：> 65岁接受auto-HCT的患者（n = 60），≤65岁接受auto-HCT的患者（n = 235）， > 65岁未接受auto-HCT的患者（n = 59）。来自TriNetX的验证队列包括5087名65岁以下和10667名≤65岁接受auto-HCT的患者，以及54757名65岁未接受auto-HCT的患者。主要结局包括无进展生存期（PFS）、到下一次治疗的时间（TNT）、总生存期（OS）和非复发死亡率（NRM）。结论：Auto-HCT改善了部分老年患者的PFS和OS。6年PFS为45.0% (> 65)vs 55.0%(≤65)(HR 1.25, P = 0.365)， 6年OS为57.8% (> 65)vs 81.1%(≤65)（HR 2.11, P = 0.025）。TNT发生率相似（64.4% vs. 63.6%; HR 0.93; P < 0.01）。毒性和死亡率相当。这些发现支持auto-HCT作为一种有价值的巩固治疗在选定的老年MM患者，强调需要个性化的策略来优化结果。
{"title":"A Large-Scale Analysis of Autologous Stem Cell Transplantation for Multiple Myeloma Patients Older than 65 Years","authors":"Adolfo Jesús Sáez-Marín , Gema Hernandez-Ibarbu , Lucia Medina Alba , Reyes Mas Babio , Andrea Tamayo , Ana Cuervo Fonseca , Jose María Sanchez-Pina , Rafael Alberto Alonso-Fernández , Nieves Lopez-Muñoz , Alberto Blanco , Pablo Justo , Noelia Garcia-Barrio , Alberto Tato , Juan Luis Cruz , David Perez-Rey , Ana Jimenez-Ubieto , Javier de la Cruz , María Calbacho , Joaquín Martínez-López","doi":"10.1016/j.clml.2025.10.021","DOIUrl":"10.1016/j.clml.2025.10.021","url":null,"abstract":"<div><h3>Introduction</h3><div>The role of autologous hematopoietic stem cell transplantation (auto-HCT) in multiple myeloma (MM) patients over 65 years remains unclear due to their underrepresentation in clinical trials. This study evaluates the safety and efficacy of auto-HCT in this population using real-world data from the TriNetX network.</div></div><div><h3>Methods</h3><div>A retrospective cohort study was conducted on MM patients treated at Hospital 12 de Octubre (2013-2023). Three cohorts were analyzed: patients > 65 years undergoing auto-HCT (n = 60), ≤ 65 years with auto-HCT (n = 235), and > 65 years without auto-HCT (n = 59). A validation cohort from TriNetX included 5087 patients > 65 and 10,667 ≤ 65 years receiving auto-HCT, along with 54,757 > 65 years without auto-HCT. Primary outcomes included progression-free survival (PFS), time to next treatment (TNT), overall survival (OS), and non-relapse mortality (NRM).</div></div><div><h3>Conclusion</h3><div>Auto-HCT improved PFS and OS in selected elderly patients. The 6-year PFS was 45.0% (> 65) versus 55.0% (≤ 65) (HR 1.25; P = .365), and the 6-year OS was 57.8% (> 65) versus 81.1% (≤ 65) (HR 2.11; P = .025). TNT rates were similar (64.4% vs. 63.6%; HR 0.93; P < .01). Toxicity and mortality were comparable. These findings support auto-HCT as a valuable consolidation therapy in selected elderly MM patients, emphasizing the need for personalized strategies to optimize outcomes.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"26 2","pages":"Pages 106-114.e5"},"PeriodicalIF":2.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.clml.2025.10.011
Lukas L. Lauer, Craig A. Portell MD
Introduction
Follicular lymphoma typically affects patients in their fifth, sixth, and seventh decades of life and carries a median survival of 10 years. Rituximab induction followed by maintenance has been increasingly used in follicular lymphoma for patients with low tumor burden progression who wish to receive treatment but want to avoid the side effect profile of chemotherapy. Data on the efficacy of this course is limited for patients previously treated with rituximab as well as those with intermediate risk disease. Here we present data from a single center on the efficacy of induction and maintenance rituximab in a cohort with a mix of intermediate and low risk patients.
Patients and Methods
26 patients with FL underwent a course of induction rituximab followed by maintenance from 2007 to 2024. 15% were bulky by GELF, 27% were high risk by FLIPI, and 35% had received prior treatment with all but one of the previously treated patients having received rituximab.
Results
Estimated median 2 year PFS was 71%, TTNT was 68%, and OS was 88%. Median follow up time was 1.72 years. Eight patients deepened their response during maintenance to a CR.
Conclusion
In this study, intermediate and low risk FL patients responded well to induction rituximab followed by maintenance with survival comparable to past studies of higher risk patients. This study provides evidence that even those patients previously treated with rituximab can benefit from retreatment rituximab with maintenance.
{"title":"Maintenance Rituximab Following Rituximab Induction for Follicular Lymphoma: A Single-Center Experience","authors":"Lukas L. Lauer, Craig A. Portell MD","doi":"10.1016/j.clml.2025.10.011","DOIUrl":"10.1016/j.clml.2025.10.011","url":null,"abstract":"<div><h3>Introduction</h3><div>Follicular lymphoma typically affects patients in their fifth, sixth, and seventh decades of life and carries a median survival of 10 years. Rituximab induction followed by maintenance has been increasingly used in follicular lymphoma for patients with low tumor burden progression who wish to receive treatment but want to avoid the side effect profile of chemotherapy. Data on the efficacy of this course is limited for patients previously treated with rituximab as well as those with intermediate risk disease. Here we present data from a single center on the efficacy of induction and maintenance rituximab in a cohort with a mix of intermediate and low risk patients.</div></div><div><h3>Patients and Methods</h3><div>26 patients with FL underwent a course of induction rituximab followed by maintenance from 2007 to 2024. 15% were bulky by GELF, 27% were high risk by FLIPI, and 35% had received prior treatment with all but one of the previously treated patients having received rituximab.</div></div><div><h3>Results</h3><div>Estimated median 2 year PFS was 71%, TTNT was 68%, and OS was 88%. Median follow up time was 1.72 years. Eight patients deepened their response during maintenance to a CR.</div></div><div><h3>Conclusion</h3><div>In this study, intermediate and low risk FL patients responded well to induction rituximab followed by maintenance with survival comparable to past studies of higher risk patients. This study provides evidence that even those patients previously treated with rituximab can benefit from retreatment rituximab with maintenance.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"26 2","pages":"Pages e292-e297"},"PeriodicalIF":2.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145457859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.clml.2025.11.003
Giuseppe Bertuglia , Elisa Seneca , Timothy Corbett , James Croft , Pawel Kaczmarek , Lauren Ellis , Chin Neoh , Edward Renaudon-Smith , Lewis Vanhinsbergh , Jindriska Lindsay , Stefania Bonetto , Sigurdur Y Kristinsson , Dingle Spence , Guy Pratt , Graham Jackson , Mark Ethell , Emma Nicholson , Christina Messiou , Tommy Brown , Leonora Conneely , Martin F. Kaiser MD
Background
Daratumumab, bortezomib, thalidomide, and dexamethasone (Dara-VTd) is the current standard of care in Europe based on the CASSIOPEIA study, which demonstrated improved depth of response and progression-free survival when daratumumab is added to VTd.
Patients and Methods
We conducted a retrospective analysis of patients treated with VTd or Dara-VTd at the Royal Marsden Hospital (RMH). Post-transplant response was assessed by biochemical response and minimal residual disease (MRD) using flow cytometry (sensitivity 10⁻⁵), with additional stratification by cytogenetic risk.
Results
A total of 173 patients (103 Dara-VTd, 70 VTd) with balanced baseline characteristics were included; 150 patients (87%) had a full cytogenetic panel. Median follow-up was 18.6 months. Post-transplant overall response rate was higher with Dara-VTd than VTd (97.1% vs. 87.1%), as was MRD negativity (78.6% vs. 55.7%). While Dara-VTd consistently outperformed VTd, the benefit decreased in patients with multiple high-risk cytogenetic abnormalities. Twenty-four-month progression-free survival was 97.3%, 94.1%, and 63.9% for patients with 0, 1, and ≥ 2 abnormalities treated with Dara-VTd, compared with 82.6%, 61.9%, and 55.6% for VTd, respectively.
Conclusion
Adding daratumumab to VTd improves post-transplant response and MRD negativity in real-world practice. The magnitude of benefit diminishes with increasing numbers of high-risk cytogenetic abnormalities, supporting the value of risk-adapted strategies and real-world MRD assessment in treatment evaluation.
背景：基于CASSIOPEIA研究，达拉单抗、硼替佐米、沙利度胺和地塞米松（Dara-VTd）是欧洲目前的标准治疗方案，该研究表明，当达拉单抗加入VTd时，反应深度和无进展生存期得到改善。患者和方法：我们对在皇家马斯登医院（RMH）接受VTd或Dara-VTd治疗的患者进行了回顾性分析。移植后反应通过生化反应和流式细胞术最小残留病（MRD）进行评估（灵敏度10⁻- 5），并通过细胞遗传学风险进行额外分层。结果：共纳入基线特征平衡的173例患者（Dara-VTd 103例，VTd 70例）；150例患者（87%）有完整的细胞遗传学检查。中位随访时间为18.6个月。移植后Dara-VTd的总有效率高于VTd (97.1% vs. 87.1%)， MRD阴性（78.6% vs. 55.7%）。虽然Dara-VTd的疗效一直优于VTd，但在患有多种高危细胞遗传学异常的患者中，疗效有所下降。接受Dara-VTd治疗的0、1和≥2例异常患者的24个月无进展生存率分别为97.3%、94.1%和63.9%，而VTd患者的无进展生存率分别为82.6%、61.9%和55.6%。结论：在现实世界的实践中，在VTd中加入达拉单抗可改善移植后反应和MRD阴性反应。随着高风险细胞遗传学异常数量的增加，获益程度逐渐降低，这支持了风险适应策略和现实世界MRD评估在治疗评估中的价值。
{"title":"Evaluating the Real-World Value of Daratumumab Addition to Multiple Myeloma Induction Therapy by Real-World Minimal Residual Disease Assessment and Extended Genetic Profiling","authors":"Giuseppe Bertuglia , Elisa Seneca , Timothy Corbett , James Croft , Pawel Kaczmarek , Lauren Ellis , Chin Neoh , Edward Renaudon-Smith , Lewis Vanhinsbergh , Jindriska Lindsay , Stefania Bonetto , Sigurdur Y Kristinsson , Dingle Spence , Guy Pratt , Graham Jackson , Mark Ethell , Emma Nicholson , Christina Messiou , Tommy Brown , Leonora Conneely , Martin F. Kaiser MD","doi":"10.1016/j.clml.2025.11.003","DOIUrl":"10.1016/j.clml.2025.11.003","url":null,"abstract":"<div><h3>Background</h3><div>Daratumumab, bortezomib, thalidomide, and dexamethasone (Dara-VTd) is the current standard of care in Europe based on the CASSIOPEIA study, which demonstrated improved depth of response and progression-free survival when daratumumab is added to VTd.</div></div><div><h3>Patients and Methods</h3><div>We conducted a retrospective analysis of patients treated with VTd or Dara-VTd at the Royal Marsden Hospital (RMH). Post-transplant response was assessed by biochemical response and minimal residual disease (MRD) using flow cytometry (sensitivity 10⁻⁵), with additional stratification by cytogenetic risk.</div></div><div><h3>Results</h3><div>A total of 173 patients (103 Dara-VTd, 70 VTd) with balanced baseline characteristics were included; 150 patients (87%) had a full cytogenetic panel. Median follow-up was 18.6 months. Post-transplant overall response rate was higher with Dara-VTd than VTd (97.1% vs. 87.1%), as was MRD negativity (78.6% vs. 55.7%). While Dara-VTd consistently outperformed VTd, the benefit decreased in patients with multiple high-risk cytogenetic abnormalities. Twenty-four-month progression-free survival was 97.3%, 94.1%, and 63.9% for patients with 0, 1, and ≥ 2 abnormalities treated with Dara-VTd, compared with 82.6%, 61.9%, and 55.6% for VTd, respectively.</div></div><div><h3>Conclusion</h3><div>Adding daratumumab to VTd improves post-transplant response and MRD negativity in real-world practice. The magnitude of benefit diminishes with increasing numbers of high-risk cytogenetic abnormalities, supporting the value of risk-adapted strategies and real-world MRD assessment in treatment evaluation.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"26 2","pages":"Pages e188-e200.e5"},"PeriodicalIF":2.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145630941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Over the last 2 decades, progress in research, treatment approaches, and market dynamics have influenced our treatment of chronic myeloid leukemia in chronic phase (CML-CP). The choice of frontline therapy depends on the treatment goal (normalizing survival only or achieving a treatment-free remission [TFR]), the toxicity profile of each BCR::ABL1 tyrosine kinase inhibitor (TKI), the patient’s comorbidities, and the cost and affordability of the treatment. When overall survival is the aim of therapy, generics of imatinib and of second-generation BCR::ABL1 TKIs offer an excellent treatment value. For patients with high-risk CML-CP or those aiming for TFR, second-generation TKIs might be the optimal frontline strategy. Challenges persist in ensuring universal access to therapy, particularly for patients in poorer conditions or geographies. With cost-effective generics now accessible, all patients with CML-CP should have the opportunity to receive imatinib (price < $1000/year worldwide), and most can have access to safe and effective second-generation TKIs. This still may not be possible in the United States and in other nations where second-generation TKIs, even generics, are still too expensive and of poor “treatment value.” Strategies such as dose optimization can enhance the TKI affordability without compromising efficacy, particularly for elderly or low-risk patients. For a novel TKI to become established frontline therapy, it should improve the durable deep molecular response rate (BCR::ABL1 transcripts on the International Scale < 0.01% for ≥ 2 years), demonstrate a favorable safety profile, and provide a good treatment value (cost versus efficacy and safety benefits).
{"title":"SOHO State of the Art Updates and Next Questions | Choosing the Best Frontline BCR::ABL1 Tyrosine Kinase Inhibitor in Chronic Myeloid Leukemia—How to Define the Treatment Value?","authors":"Fadi G. Haddad , Elias Jabbour , Massimo Breccia , Rüdiger Hehlmann , Hemant Malhotra , Franck Emmanuel Nicolini , Leif Stenke , Hagop Kantarjian","doi":"10.1016/j.clml.2025.10.001","DOIUrl":"10.1016/j.clml.2025.10.001","url":null,"abstract":"<div><div>Over the last 2 decades, progress in research, treatment approaches, and market dynamics have influenced our treatment of chronic myeloid leukemia in chronic phase (CML-CP). The choice of frontline therapy depends on the treatment goal (normalizing survival only or achieving a treatment-free remission [TFR]), the toxicity profile of each BCR::ABL1 tyrosine kinase inhibitor (TKI), the patient’s comorbidities, and the cost and affordability of the treatment. When overall survival is the aim of therapy, generics of imatinib and of second-generation BCR::ABL1 TKIs offer an excellent treatment value. For patients with high-risk CML-CP or those aiming for TFR, second-generation TKIs might be the optimal frontline strategy. Challenges persist in ensuring universal access to therapy, particularly for patients in poorer conditions or geographies. With cost-effective generics now accessible, all patients with CML-CP should have the opportunity to receive imatinib (price < $1000/year worldwide), and most can have access to safe and effective second-generation TKIs. This still may not be possible in the United States and in other nations where second-generation TKIs, even generics, are still too expensive and of poor “treatment value.” Strategies such as dose optimization can enhance the TKI affordability without compromising efficacy, particularly for elderly or low-risk patients. For a novel TKI to become established frontline therapy, it should improve the durable deep molecular response rate (<em>BCR::ABL1</em> transcripts on the International Scale < 0.01% for ≥ 2 years), demonstrate a favorable safety profile, and provide a good treatment value (cost versus efficacy and safety benefits).</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"26 2","pages":"Pages 57-65"},"PeriodicalIF":2.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145371989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.clml.2025.10.010
Javier Munoz , Allison Rosenthal , Andrew Ip , Justin M. Darrah , Tongsheng Wang , Guihua Zhang , Alex Mutebi , Tychell Branchcomb , Zhijie Ding , Anindit Chhibber , Fernando Rivas Navarro , Malene Risum , Mohammad Atiya , Samantha Brodkin , Anthony Wang , Abualbishr Alshreef , Diala Harb , Mariana Sacchi , Daniela Hoehn , Yasmin H. Karimi
Background
This indirect treatment comparison evaluated epcoritamab plus gemcitabine and oxaliplatin (Epcor+GemOx) versus rituximab (R)-GemOx in patients with transplant-ineligible relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL).
Methods
Individual patient data (IPD) for Epcor+GemOx from EPCORE NHL-2 Arm 5 (NCT04663347) were compared with clinical practice data for patients treated with R-GemOx using 2 methodologies: a matching-adjusted indirect comparison (MAIC) using published aggregate data from clinical sites in France (Cazelles et al. Lymphoma. 2021;62:2161) and inverse probability of treatment weighting (IPTW) using IPD from the US-based COTA database (COTA Healthcare). Outcomes included objective response rate (ORR), complete response (CR) rate, progression-free survival (PFS), and overall survival (OS).
Results
In the MAIC, after adjustment, Epcor+GemOx versus R-GemOx had significantly higher ORR (86.8% vs 38.3%; relative risk [RR], 2.27 [95% confidence interval (CI), 1.76-2.93]; P < .0001) and CR rate (71.2% vs 32.7%; RR, 2.18 [95% CI, 1.61-2.96]; P < .0001). Median PFS was 26.7 versus 4.8 months (hazard ratio [HR], 0.38 [95% CI, 0.22-0.67]; P < .001); median OS was not reached with Epcor+GemOx versus 10.0 months with R-GemOx (HR, 0.54 [95% CI, 0.29-1.00]; P = .05). In the IPTW, Epcor+GemOx versus R-GemOx had significantly higher ORR (88.5% vs 35.6%; RR, 2.48 [95% CI, 1.80-3.43]; P < .0001), CR rate (63.9% vs 10.2%; RR, 6.25 [95% CI, 3.08-12.68]; P < .0001), median PFS (11.2 vs 2.4 months; HR, 0.23 [95% CI, 0.15-0.36]; P < .001), and median OS (21.6 vs 8.3 months; HR, 0.47 [95% CI, 0.30-0.74]; P = .002).
Conclusion
Epcor+GemOx provides significantly greater response rates and survival outcomes compared with R-GemOx in patients with transplant-ineligible R/R DLBCL.
背景：这项间接治疗比较评估了依可利他单抗联合吉西他滨和奥沙利铂（Epcor+GemOx）与利妥昔单抗(R)-GemOx对不适合移植的复发/难治性（R/R）弥漫性大b细胞淋巴瘤（DLBCL）患者的治疗效果。方法：EPCORE nll -2 Arm 5 （NCT04663347）的Epcor+GemOx的个体患者数据（IPD）与接受R-GemOx治疗的患者的临床实践数据使用两种方法进行比较：匹配调整间接比较（MAIC）使用来自法国临床站点的已发表的汇总数据（Cazelles等）；淋巴瘤。2021;62:2161)和使用来自美国COTA数据库（COTA Healthcare）的IPD的治疗加权逆概率（IPTW）。结果包括客观缓解率（ORR）、完全缓解率（CR）、无进展生存期（PFS）和总生存期（OS）。结果：在MAIC中，调整后Epcor+GemOx与R-GemOx的ORR显著高于前者（86.8% vs 38.3%），相对危险度[RR]为2.27[95%可信区间（CI）， 1.76 ~ 2.93]；P < 0.0001)和CR率（71.2% vs 32.7%； RR, 2.18 [95% CI, 1.61 ~ 2.96]; P < 0.0001）。中位PFS为26.7 vs 4.8个月（风险比[HR]， 0.38 [95% CI, 0.22-0.67]; P < .001）；Epcor+GemOx组未达到中位总生存期，而R-GemOx组为10.0个月（HR, 0.54 [95% CI, 0.29-1.00]; P = 0.05）。在IPTW中，Epcor+GemOx与R-GemOx的ORR （88.5% vs 35.6%； RR, 2.48 [95% CI, 1.80-3.43]; P < 0.0001）、CR率（63.9% vs 10.2%； RR, 6.25 [95% CI, 3.08-12.68]; P < 0.0001）、中位PFS （11.2 vs 2.4个月；HR, 0.23 [95% CI, 0.15-0.36]; P < 0.001）和中位OS （21.6 vs 8.3个月；HR, 0.47 [95% CI, 0.30-0.74]; P = 0.002）显著高于R-GemOx。结论：与R-GemOx相比，Epcor+GemOx在移植不合格的R/R DLBCL患者中提供了显着更高的缓解率和生存结果。
{"title":"Epcoritamab Plus Gemcitabine and Oxaliplatin Versus Rituximab Plus Gemcitabine and Oxaliplatin in Transplant-Ineligible Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Match-Adjusted Comparative Analysis","authors":"Javier Munoz , Allison Rosenthal , Andrew Ip , Justin M. Darrah , Tongsheng Wang , Guihua Zhang , Alex Mutebi , Tychell Branchcomb , Zhijie Ding , Anindit Chhibber , Fernando Rivas Navarro , Malene Risum , Mohammad Atiya , Samantha Brodkin , Anthony Wang , Abualbishr Alshreef , Diala Harb , Mariana Sacchi , Daniela Hoehn , Yasmin H. Karimi","doi":"10.1016/j.clml.2025.10.010","DOIUrl":"10.1016/j.clml.2025.10.010","url":null,"abstract":"<div><h3>Background</h3><div>This indirect treatment comparison evaluated epcoritamab plus gemcitabine and oxaliplatin (Epcor+GemOx) versus rituximab (R)-GemOx in patients with transplant-ineligible relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL).</div></div><div><h3>Methods</h3><div>Individual patient data (IPD) for Epcor+GemOx from EPCORE NHL-2 Arm 5 (NCT04663347) were compared with clinical practice data for patients treated with R-GemOx using 2 methodologies: a matching-adjusted indirect comparison (MAIC) using published aggregate data from clinical sites in France (Cazelles et al. <em>Lymphoma</em>. 2021;62:2161) and inverse probability of treatment weighting (IPTW) using IPD from the US-based COTA database (COTA Healthcare). Outcomes included objective response rate (ORR), complete response (CR) rate, progression-free survival (PFS), and overall survival (OS).</div></div><div><h3>Results</h3><div>In the MAIC, after adjustment, Epcor+GemOx versus R-GemOx had significantly higher ORR (86.8% vs 38.3%; relative risk [RR], 2.27 [95% confidence interval (CI), 1.76-2.93]; <em>P</em> < .0001) and CR rate (71.2% vs 32.7%; RR, 2.18 [95% CI, 1.61-2.96]; <em>P</em> < .0001). Median PFS was 26.7 versus 4.8 months (hazard ratio [HR], 0.38 [95% CI, 0.22-0.67]; <em>P</em> < .001); median OS was not reached with Epcor+GemOx versus 10.0 months with R-GemOx (HR, 0.54 [95% CI, 0.29-1.00]; <em>P</em> = .05). In the IPTW, Epcor+GemOx versus R-GemOx had significantly higher ORR (88.5% vs 35.6%; RR, 2.48 [95% CI, 1.80-3.43]; <em>P</em> < .0001), CR rate (63.9% vs 10.2%; RR, 6.25 [95% CI, 3.08-12.68]; <em>P</em> < .0001), median PFS (11.2 vs 2.4 months; HR, 0.23 [95% CI, 0.15-0.36]; <em>P</em> < .001), and median OS (21.6 vs 8.3 months; HR, 0.47 [95% CI, 0.30-0.74]; <em>P</em> = .002).</div></div><div><h3>Conclusion</h3><div>Epcor+GemOx provides significantly greater response rates and survival outcomes compared with R-GemOx in patients with transplant-ineligible R/R DLBCL.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"26 2","pages":"Pages e283-e291"},"PeriodicalIF":2.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145476795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.clml.2025.10.027
Joseph Brandwein, David Page, Elena Liew, Jennifer Croden, Peng Wang
Methods
The outcomes of all newly diagnosed acute myeloid leukemia (AML) patients treated with intensive chemotherapy (IC) at a single center between 2018 and 2024 were evaluated.
Results
The complete remission (CR) rates were not significantly different between ELN2022 favorable (fav) versus intermediate (int) risk patients. Of patients achieving CR, 81% of int risk and 85% of adverse (adv) risk patients intended for allogeneic stem cell transplant (HSCT) underwent HSCT in CR1. The overall survival (OS) and relapse-free survival (RFS) were not significantly different between ELN fav versus int risk patients. In contrast, OS was significantly worse in ELN adv risk patients, including those who underwent HSCT, due to both lower CR and higher relapse rates. Within the ELN adv group, patients with RUNX1 mutations had a superior OS compared with other myelodysplasia-related (MR) mutations or adv risk cytogenetics without RUNX1. TP53 mutated patients had the worst outcome. Based on these results, a transplant-adjusted prognostic scoring system was devised, incorporating HSCT into an integrated postremission strategy. In this model, ELN fav and int risk patients were considered good risk, RUNX1mut and KMT2Ar patients intermediate risk, other ELN adv non-TP53 mutated patients poor risk, and TP53 mutated patients very poor risk. The 5-year OS in these groups was 78%, 54%, 22% and 0%, respectively (P < .001).
Conclusions
This revised classification provides a better discrimination of prognostic groups as compared with ELN2022, likely due to the high rate of HSCT now achievable for ELN int risk patients. However, results in ELN adv risk patients remain suboptimal.
{"title":"Proposed Modifications to Prognostic Classification of AML Patients Treated With Intensive Chemotherapy Based on Recent Real-World Data","authors":"Joseph Brandwein, David Page, Elena Liew, Jennifer Croden, Peng Wang","doi":"10.1016/j.clml.2025.10.027","DOIUrl":"10.1016/j.clml.2025.10.027","url":null,"abstract":"<div><h3>Methods</h3><div>The outcomes of all newly diagnosed acute myeloid leukemia (AML) patients treated with intensive chemotherapy (IC) at a single center between 2018 and 2024 were evaluated.</div></div><div><h3>Results</h3><div>The complete remission (CR) rates were not significantly different between ELN2022 favorable (fav) versus intermediate (int) risk patients. Of patients achieving CR, 81% of int risk and 85% of adverse (adv) risk patients intended for allogeneic stem cell transplant (HSCT) underwent HSCT in CR1. The overall survival (OS) and relapse-free survival (RFS) were not significantly different between ELN fav versus int risk patients. In contrast, OS was significantly worse in ELN adv risk patients, including those who underwent HSCT, due to both lower CR and higher relapse rates. Within the ELN adv group, patients with <em>RUNX1</em> mutations had a superior OS compared with other myelodysplasia-related (MR) mutations or adv risk cytogenetics without <em>RUNX1. TP53</em> mutated patients had the worst outcome. Based on these results, a transplant-adjusted prognostic scoring system was devised, incorporating HSCT into an integrated postremission strategy. In this model, ELN fav and int risk patients were considered good risk, <em>RUNX1mut</em> and <em>KMT2Ar</em> patients intermediate risk, other ELN adv non-<em>TP53</em> mutated patients poor risk, and <em>TP53</em> mutated patients very poor risk. The 5-year OS in these groups was 78%, 54%, 22% and 0%, respectively (<em>P</em> < .001).</div></div><div><h3>Conclusions</h3><div>This revised classification provides a better discrimination of prognostic groups as compared with ELN2022, likely due to the high rate of HSCT now achievable for ELN int risk patients. However, results in ELN adv risk patients remain suboptimal.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"26 2","pages":"Pages e180-e187.e8"},"PeriodicalIF":2.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.clml.2025.10.004
Maria Gavriatopoulou , Sotirios Manganas , Ioannis Ntanasis-Stathopoulos , Meletios-Athanasios Dimopoulos
Multiple myeloma increasingly presents with multi-class drug resistance after frontline treatment. Although chimeric antigen receptor (CAR) T-cells have emerged as a highly effective treatment modality available at first relapse, their widespread adoption has been hindered by high costs and complicated logistics. We collected evidence from randomized phase III clinical trials, subgroup analyses, and recent guidelines to form an evidence-based, non CAR-T treatment framework. The main determinant of second-line therapy selection includes refractoriness, particularly to lenalidomide and anti-CD38 monoclonal antibodies, followed by cytogenetic risk, relapse aggressiveness, frailty, and patient preferences. In lenalidomide-sensitive or naive patients, regimens that combine an anti-CD38 monoclonal antibody with an immunomodulatory drug (IMiD) or a proteasome inhibitor provide the most consistent benefit. In lenalidomide-refractory patients, non-lenalidomide containing combinations are preferred. Moreover, anti-CD38 antibody refractory relapse excludes further anti-CD38 antibody use in second-line combinations. Due to anti-CD38 antibody incorporation in frontline regimens, refractoriness to this drug class is becoming increasingly prevalent, necessitating the use of novel approaches. Combinations based on belantamab mafadotin, an antibody drug conjugate targeting B cell maturation antigen (BCMA), are currently the leading non CAR-T options in this setting, while exportin-1 inhibitors, such as selinexor, and next-generation proteasome inhibitors offer additional options. Ongoing trials assessing T-cell redirecting bispecific antibodies targeting B cell maturation antigen or GPRC5D may further improve outcomes at first relapse as access and safety profiles evolve. In conclusion, early-relapse multiple myeloma care should be individualized in order to optimize patient outcomes and achieve long-term remissions with acceptable toxicity profile.
{"title":"SOHO State of the Art Updates and Next Questions | Treatment of Myeloma Early Relapse: Non-CAR T Cell","authors":"Maria Gavriatopoulou , Sotirios Manganas , Ioannis Ntanasis-Stathopoulos , Meletios-Athanasios Dimopoulos","doi":"10.1016/j.clml.2025.10.004","DOIUrl":"10.1016/j.clml.2025.10.004","url":null,"abstract":"<div><div>Multiple myeloma increasingly presents with multi-class drug resistance after frontline treatment. Although chimeric antigen receptor (CAR) T-cells have emerged as a highly effective treatment modality available at first relapse, their widespread adoption has been hindered by high costs and complicated logistics. We collected evidence from randomized phase III clinical trials, subgroup analyses, and recent guidelines to form an evidence-based, non CAR-T treatment framework. The main determinant of second-line therapy selection includes refractoriness, particularly to lenalidomide and anti-CD38 monoclonal antibodies, followed by cytogenetic risk, relapse aggressiveness, frailty, and patient preferences. In lenalidomide-sensitive or naive patients, regimens that combine an anti-CD38 monoclonal antibody with an immunomodulatory drug (IMiD) or a proteasome inhibitor provide the most consistent benefit. In lenalidomide-refractory patients, non-lenalidomide containing combinations are preferred. Moreover, anti-CD38 antibody refractory relapse excludes further anti-CD38 antibody use in second-line combinations. Due to anti-CD38 antibody incorporation in frontline regimens, refractoriness to this drug class is becoming increasingly prevalent, necessitating the use of novel approaches. Combinations based on belantamab mafadotin, an antibody drug conjugate targeting B cell maturation antigen (BCMA), are currently the leading non CAR-T options in this setting, while exportin-1 inhibitors, such as selinexor, and next-generation proteasome inhibitors offer additional options. Ongoing trials assessing T-cell redirecting bispecific antibodies targeting B cell maturation antigen or GPRC5D may further improve outcomes at first relapse as access and safety profiles evolve. In conclusion, early-relapse multiple myeloma care should be individualized in order to optimize patient outcomes and achieve long-term remissions with acceptable toxicity profile.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"26 2","pages":"Pages 66-72"},"PeriodicalIF":2.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145426760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.clml.2025.10.009
Amanda Caruso , Filomena Emanuela Laddaga , Alba Fiorentino , Angela Maria Moramarco , Flavia Carbone , Clorinda Maria Luisa Derosa , Stefano Martinotti , Francesco Gaudio
Secondary breast cancer (SBC) is emerging as the most frequent solid tumour in female survivors of Hodgkin lymphoma (HL) treated with chest radiotherapy (RT). Women irradiated with ≥10 Gy before the age of 30 accumulate risks that rival those carried by BRCA1/2 mutation carriers, with excess cases appearing ∼8 years after RT and persisting lifelong. This review weaves together epidemiological data, mechanistic evidence and clinical studies to elucidate how radiation dose and field, age at exposure, systemic regimens, host genomics and micro-environmental factors interact to drive SBC. Radiation-associated tumours display a distinctive profile—earlier onset, frequent bilaterality—posing unique therapeutic and prognostic challenges. We discuss current surveillance recommendations of annual mammography plus breast MRI from age 25 (or 8 years post-RT) and examine preventive strategies ranging from RT de-escalation and cardioprotective chemotherapy to lifestyle modification and selective chemoprevention. Finally, we highlight emerging imaging and molecular biomarkers—most notably MRI background parenchymal enhancement and polygenic risk scores—that may enable a shift from 1-size-fits-all follow-up to precision survivorship care.
{"title":"Breast Cancer Risk After Chest Radiotherapy in Hodgkin Lymphoma Survivors: A Comprehensive Overview","authors":"Amanda Caruso , Filomena Emanuela Laddaga , Alba Fiorentino , Angela Maria Moramarco , Flavia Carbone , Clorinda Maria Luisa Derosa , Stefano Martinotti , Francesco Gaudio","doi":"10.1016/j.clml.2025.10.009","DOIUrl":"10.1016/j.clml.2025.10.009","url":null,"abstract":"<div><div>Secondary breast cancer (SBC) is emerging as the most frequent solid tumour in female survivors of Hodgkin lymphoma (HL) treated with chest radiotherapy (RT). Women irradiated with ≥10 Gy before the age of 30 accumulate risks that rival those carried by BRCA1/2 mutation carriers, with excess cases appearing ∼8 years after RT and persisting lifelong. This review weaves together epidemiological data, mechanistic evidence and clinical studies to elucidate how radiation dose and field, age at exposure, systemic regimens, host genomics and micro-environmental factors interact to drive SBC. Radiation-associated tumours display a distinctive profile—earlier onset, frequent bilaterality—posing unique therapeutic and prognostic challenges. We discuss current surveillance recommendations of annual mammography plus breast MRI from age 25 (or 8 years post-RT) and examine preventive strategies ranging from RT de-escalation and cardioprotective chemotherapy to lifestyle modification and selective chemoprevention. Finally, we highlight emerging imaging and molecular biomarkers—most notably MRI background parenchymal enhancement and polygenic risk scores—that may enable a shift from 1-size-fits-all follow-up to precision survivorship care.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"26 2","pages":"Pages e270-e282"},"PeriodicalIF":2.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145457854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.clml.2025.10.005
Cinnie Soekojo , Shimin Jasmine Chung , Ming-Tao Tsai , Wenming Chen , Jeffrey Huang , Jin Seok Kim , Dong-Gun Lee , Chang Ki Min , Kazuhito Suzuki , Subramanian Swaminathan , Hiroyuki Takamatsu , Daryl Tan , Uday Yanamandra , Chandramouli Nagarajan , Wee Joo Chng
Background
The management of relapsed / refractory myeloma particularly those who are heavily pretreated and penta-refractory has experienced a paradigm change with the advent of bispecific antibodies targeting B-cell maturation antigen (BCMA), offering new hope for these patients. The diverse experiences in the use of bispecific antibodies across Asian countries/regions underscore the complexities of integrating these therapies into clinical practice. With limited availability and varying access through clinical trials, compassionate access programmes and early commercial use, these agents are demonstrating impressive efficacy, yet present unique challenges in widespread adoption of these agents.
Methods
A roundtable discussion among myeloma experts from Asia has highlighted consistent efficacy but also raised concerns about the durability of response and the management of associated toxicities and infections.
Results
These discussions emphasize the need for ongoing research to better understand the nuances of treatment sequencing and patient selection.
Conclusions
The insights gained will contribute to developing strategic frameworks and consensus guidelines that can effectively guide clinicians in optimizing outcomes for myeloma patients in diverse healthcare settings.
{"title":"Perspectives on Anti-BCMA Bispecific Antibodies use in Multiple Myeloma–Experience from Asian Countries","authors":"Cinnie Soekojo , Shimin Jasmine Chung , Ming-Tao Tsai , Wenming Chen , Jeffrey Huang , Jin Seok Kim , Dong-Gun Lee , Chang Ki Min , Kazuhito Suzuki , Subramanian Swaminathan , Hiroyuki Takamatsu , Daryl Tan , Uday Yanamandra , Chandramouli Nagarajan , Wee Joo Chng","doi":"10.1016/j.clml.2025.10.005","DOIUrl":"10.1016/j.clml.2025.10.005","url":null,"abstract":"<div><h3>Background</h3><div>The management of relapsed / refractory myeloma particularly those who are heavily pretreated and penta-refractory has experienced a paradigm change with the advent of bispecific antibodies targeting B-cell maturation antigen (BCMA), offering new hope for these patients. The diverse experiences in the use of bispecific antibodies across Asian countries/regions underscore the complexities of integrating these therapies into clinical practice. With limited availability and varying access through clinical trials, compassionate access programmes and early commercial use, these agents are demonstrating impressive efficacy, yet present unique challenges in widespread adoption of these agents.</div></div><div><h3>Methods</h3><div>A roundtable discussion among myeloma experts from Asia has highlighted consistent efficacy but also raised concerns about the durability of response and the management of associated toxicities and infections.</div></div><div><h3>Results</h3><div>These discussions emphasize the need for ongoing research to better understand the nuances of treatment sequencing and patient selection.</div></div><div><h3>Conclusions</h3><div>The insights gained will contribute to developing strategic frameworks and consensus guidelines that can effectively guide clinicians in optimizing outcomes for myeloma patients in diverse healthcare settings.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"26 2","pages":"Pages e241-e247"},"PeriodicalIF":2.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145476676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.clml.2025.10.017
Adam J. Olszewski
High-grade B-cell lymphomas (HGBL) represent a heterogeneous group of aggressive mature B-cell malignancies characterized by clinical, morphologic, and cytogenetic features that bridge diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma. Current classification frameworks define HGBL largely by morphology and MYC-based cytogenetics, yielding categories that are inconsistently applied and biologically incomplete. Recent gene expression profiling studies have identified a reproducible “dark-zone signature” (DZsig), present in most double-hit lymphomas and a subset of DLBCL, which portends poor outcomes and provides a more objective biological definition of HGBL. Genomic studies further demonstrate that HGBL can arise from diverse DLBCL subtypes, converging on MYC deregulation, genomic instability, and T-cell depleted immune microenvironment. Therapeutically, retrospective and phase 2 studies suggest improved outcomes with intensified regimens such as dose-adjusted EPOCH-R compared with R-CHOP, though randomized data remain limited. This review focuses on the application of DZsig and molecular classifications, applicability of the POLARIX trial data to HGBL of germinal center B cell and activated B cell subtypes, and the use of novel T-cell engaging therapies in HGBL. CAR T-cell therapy has transformed the relapsed/refractory setting, with comparable efficacy in HGBL and DLBCL. In contrast, responses to CD20xCD3 bispecific antibodies appear attenuated in HGBL-DH, though combination regimens with antibody-drug conjugates or chemotherapy show promise. Other options, including CD19-directed antibody-drug conjugates, offer some activity. Future progress will depend on replacing morphology-based criteria with biology-driven classification that incorporates DZsig and genomic subtyping, and on developing rational, mechanism-based therapies that address both tumor-intrinsic drivers and the hostile microenvironment.
{"title":"SOHO State of the Art Updates and Next Questions | Diagnosis and Management of High-Grade B-Cell Lymphomas","authors":"Adam J. Olszewski","doi":"10.1016/j.clml.2025.10.017","DOIUrl":"10.1016/j.clml.2025.10.017","url":null,"abstract":"<div><div>High-grade B-cell lymphomas (HGBL) represent a heterogeneous group of aggressive mature B-cell malignancies characterized by clinical, morphologic, and cytogenetic features that bridge diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma. Current classification frameworks define HGBL largely by morphology and <em>MYC</em>-based cytogenetics, yielding categories that are inconsistently applied and biologically incomplete. Recent gene expression profiling studies have identified a reproducible “dark-zone signature” (DZsig), present in most double-hit lymphomas and a subset of DLBCL, which portends poor outcomes and provides a more objective biological definition of HGBL. Genomic studies further demonstrate that HGBL can arise from diverse DLBCL subtypes, converging on MYC deregulation, genomic instability, and T-cell depleted immune microenvironment. Therapeutically, retrospective and phase 2 studies suggest improved outcomes with intensified regimens such as dose-adjusted EPOCH-R compared with R-CHOP, though randomized data remain limited. This review focuses on the application of DZsig and molecular classifications, applicability of the POLARIX trial data to HGBL of germinal center B cell and activated B cell subtypes, and the use of novel T-cell engaging therapies in HGBL. CAR T-cell therapy has transformed the relapsed/refractory setting, with comparable efficacy in HGBL and DLBCL. In contrast, responses to CD20xCD3 bispecific antibodies appear attenuated in HGBL-DH, though combination regimens with antibody-drug conjugates or chemotherapy show promise. Other options, including CD19-directed antibody-drug conjugates, offer some activity. Future progress will depend on replacing morphology-based criteria with biology-driven classification that incorporates DZsig and genomic subtyping, and on developing rational, mechanism-based therapies that address both tumor-intrinsic drivers and the hostile microenvironment.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"26 2","pages":"Pages e157-e163"},"PeriodicalIF":2.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145502489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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