Pub Date : 2026-03-10DOI: 10.1038/s41408-026-01459-1
Qihua Zou, Yi Cao, Liang Wang, Wuping Li, Qingsong Yin, Yudan Wu, Hongmei Jing, Zhigang Peng, Xiuhua Sun, Jun Rao, Ying Chen, Hongyu Zhang, Dongfeng Zeng, Bingzong Li, Ying Zhao, Xudong Zhang, Yuchen Zhang, Yan Gao, Bing Bai, Yi Xia, Yu Fang, Zouxiang Chen, Man Nie, Xiaojie Fang, Shenrui Bai, Huiqiang Huang, Qingqing Cai, Jun Cai
We evaluated the effectiveness of adding anti-PD-1 antibody to P-GEMOX regimen in previously untreated advanced-stage natural killer/T-cell lymphoma (NKTCL) compared to P-GEMOX alone or with autologous stem cell transplantation (ASCT). 418 patients (135 and 283 in the immunochemotherapy and chemotherapy groups, respectively) were analyzed from 15 Chinese centers (2014–2023). The median follow-up was 40.7 months. The immunochemotherapy group had a higher objective response rate (ORR) (89.6% versus 77.0%), complete response (CR) rate (77.0% versus 50.5%), 3-year progression-free survival (PFS) rate (64.1% versus 40.7%), and 3-year overall survival (OS) rate (79.5% versus 60.8%) compared to the chemotherapy group. Grade 3–4 neutropenia was more common in the immunochemotherapy group (40.0% versus 20.8% in the chemotherapy group, p < 0.001). Grade 3–4 hematologic toxicities were prevalent during ASCT, whereas anti-PD-1 maintenance was well tolerated. Grade ≥3 non-hematologic adverse events during anti-PD-1 maintenance were rare. In propensity score-matched (PSM) analysis of patients achieving CR after induction (n = 41 per group), the 3-year disease-free survival (DFS) rate was 72.6% for immunochemotherapy plus anti-PD-1 maintenance versus 50.9% for chemotherapy plus ASCT (p = 0.032), and the 3-year OS rate was 91.5% versus 72.9% (p = 0.029). First-line anti-PD-1 antibody plus P-GEMOX followed by anti-PD-1 maintenance shows better response and survival over P-GEMOX chemotherapy alone and P-GEMOX with ASCT, while maintaining acceptable toxicity.
{"title":"Anti-PD-1 antibody combined with P-GEMOX chemotherapy versus P-GEMOX chemotherapy with or without autologous stem-cell transplantation for previously untreated advanced natural killer/T cell lymphoma: a retrospective cohort study","authors":"Qihua Zou, Yi Cao, Liang Wang, Wuping Li, Qingsong Yin, Yudan Wu, Hongmei Jing, Zhigang Peng, Xiuhua Sun, Jun Rao, Ying Chen, Hongyu Zhang, Dongfeng Zeng, Bingzong Li, Ying Zhao, Xudong Zhang, Yuchen Zhang, Yan Gao, Bing Bai, Yi Xia, Yu Fang, Zouxiang Chen, Man Nie, Xiaojie Fang, Shenrui Bai, Huiqiang Huang, Qingqing Cai, Jun Cai","doi":"10.1038/s41408-026-01459-1","DOIUrl":"https://doi.org/10.1038/s41408-026-01459-1","url":null,"abstract":"We evaluated the effectiveness of adding anti-PD-1 antibody to P-GEMOX regimen in previously untreated advanced-stage natural killer/T-cell lymphoma (NKTCL) compared to P-GEMOX alone or with autologous stem cell transplantation (ASCT). 418 patients (135 and 283 in the immunochemotherapy and chemotherapy groups, respectively) were analyzed from 15 Chinese centers (2014–2023). The median follow-up was 40.7 months. The immunochemotherapy group had a higher objective response rate (ORR) (89.6% versus 77.0%), complete response (CR) rate (77.0% versus 50.5%), 3-year progression-free survival (PFS) rate (64.1% versus 40.7%), and 3-year overall survival (OS) rate (79.5% versus 60.8%) compared to the chemotherapy group. Grade 3–4 neutropenia was more common in the immunochemotherapy group (40.0% versus 20.8% in the chemotherapy group, p < 0.001). Grade 3–4 hematologic toxicities were prevalent during ASCT, whereas anti-PD-1 maintenance was well tolerated. Grade ≥3 non-hematologic adverse events during anti-PD-1 maintenance were rare. In propensity score-matched (PSM) analysis of patients achieving CR after induction (n = 41 per group), the 3-year disease-free survival (DFS) rate was 72.6% for immunochemotherapy plus anti-PD-1 maintenance versus 50.9% for chemotherapy plus ASCT (p = 0.032), and the 3-year OS rate was 91.5% versus 72.9% (p = 0.029). First-line anti-PD-1 antibody plus P-GEMOX followed by anti-PD-1 maintenance shows better response and survival over P-GEMOX chemotherapy alone and P-GEMOX with ASCT, while maintaining acceptable toxicity.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"6 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147381706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-10DOI: 10.1038/s41408-026-01458-2
Stephen M Ansell,Grzegorz S Nowakowski
Diffuse large B-cell lymphoma (DLBCL) is an aggressive B-cell malignancy and is the most common subtype of lymphoma. Treatment is administered with curative intent and approximately two thirds of patients are expected to have durable long-term survival. To achieve this, anthracycline-based chemotherapy in combination with rituximab is typically administered as initial therapy. Management is optimized based on the disease stage, prognostic clinical features, and histological or molecular subclassification. In patients with the activated B-cell subtype of DLBCL, polatuzumab vedotin is commonly included in the combination. For those with Myc and BCL-2 rearrangements, a more treatment intense approach is used. Despite this risk-adapted approach, at least one third of patients relapse. Those who relapse within 1 year, or are resistant to initial therapy typically receive chimeric antigen receptor (CAR) T-cell therapy. For those relapsing more than a year post initial treatment, salvage chemotherapy followed by an autologous stem cell transplant is offered. In patients ineligible for cellular therapy, or those who progress after CAR T-cell treatment, management is palliative and includes administration of bispecific antibodies or antibody drug conjugate combinations. To further improve the outcome of DLBCL patients, incorporation of cellular and bispecific therapies into front-line treatment is currently being tested.
{"title":"Current treatment algorithm: diffuse large B cell lymphoma.","authors":"Stephen M Ansell,Grzegorz S Nowakowski","doi":"10.1038/s41408-026-01458-2","DOIUrl":"https://doi.org/10.1038/s41408-026-01458-2","url":null,"abstract":"Diffuse large B-cell lymphoma (DLBCL) is an aggressive B-cell malignancy and is the most common subtype of lymphoma. Treatment is administered with curative intent and approximately two thirds of patients are expected to have durable long-term survival. To achieve this, anthracycline-based chemotherapy in combination with rituximab is typically administered as initial therapy. Management is optimized based on the disease stage, prognostic clinical features, and histological or molecular subclassification. In patients with the activated B-cell subtype of DLBCL, polatuzumab vedotin is commonly included in the combination. For those with Myc and BCL-2 rearrangements, a more treatment intense approach is used. Despite this risk-adapted approach, at least one third of patients relapse. Those who relapse within 1 year, or are resistant to initial therapy typically receive chimeric antigen receptor (CAR) T-cell therapy. For those relapsing more than a year post initial treatment, salvage chemotherapy followed by an autologous stem cell transplant is offered. In patients ineligible for cellular therapy, or those who progress after CAR T-cell treatment, management is palliative and includes administration of bispecific antibodies or antibody drug conjugate combinations. To further improve the outcome of DLBCL patients, incorporation of cellular and bispecific therapies into front-line treatment is currently being tested.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"299 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147381237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Multiple myeloma (MM), long viewed as incurable, is entering a transformative era marked by deeper remissions, prolonged survival, and the realistic prospect of cure. The greatest opportunity lies at diagnosis, before genomic heterogeneity and immune escape limit therapeutic impact. High-risk smoldering MM provides a preclinical window where early intervention with targeted antibodies or combinations can delay progression and, as in some trials, improve survival. Refining the threshold for treatment-entry requires integrated risk models that combine genomics, microenvironmental and immune profiling, and artificial intelligence. The therapeutic goal is sustained minimal residual disease (MRD) negativity at a sensitivity of 10⁻⁶, validated with functional imaging to exclude focal disease. Achieving two years of sustained MRD negativity in standard-risk and three years or longer in high-risk disease strongly predicts long-term progression-free survival; five years off therapy may approximate operational cure. Quadruplet induction, consolidation, and tailored maintenance regimens maximize depth and durability of response. To advance this vision, priorities include standardized MRD and imaging assays, MRD-adapted clinical trials, strategies balancing treatment toxicity with quality of life, and equitable global access. With decisive and risk-adapted strategies, achieving cure in MM within the next decade is no longer aspirational but increasingly within reach.
{"title":"Toward a cure for multiple myeloma within a decade.","authors":"Mohamad Mohty,Florent Malard,Thierry Facon,Jean-Luc Harousseau","doi":"10.1038/s41408-026-01461-7","DOIUrl":"https://doi.org/10.1038/s41408-026-01461-7","url":null,"abstract":"Multiple myeloma (MM), long viewed as incurable, is entering a transformative era marked by deeper remissions, prolonged survival, and the realistic prospect of cure. The greatest opportunity lies at diagnosis, before genomic heterogeneity and immune escape limit therapeutic impact. High-risk smoldering MM provides a preclinical window where early intervention with targeted antibodies or combinations can delay progression and, as in some trials, improve survival. Refining the threshold for treatment-entry requires integrated risk models that combine genomics, microenvironmental and immune profiling, and artificial intelligence. The therapeutic goal is sustained minimal residual disease (MRD) negativity at a sensitivity of 10⁻⁶, validated with functional imaging to exclude focal disease. Achieving two years of sustained MRD negativity in standard-risk and three years or longer in high-risk disease strongly predicts long-term progression-free survival; five years off therapy may approximate operational cure. Quadruplet induction, consolidation, and tailored maintenance regimens maximize depth and durability of response. To advance this vision, priorities include standardized MRD and imaging assays, MRD-adapted clinical trials, strategies balancing treatment toxicity with quality of life, and equitable global access. With decisive and risk-adapted strategies, achieving cure in MM within the next decade is no longer aspirational but increasingly within reach.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"54 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147383533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Long-term outcomes of autologous stem cell transplantation for AL amyloidosis: a 15-year experience from a Chinese referral center and a comparison of different eras.","authors":"Mengnan Liu,Jinzhou Guo,Wencui Chen,Xiaomei Wu,Weiwei Xu,Xianghua Huang","doi":"10.1038/s41408-026-01464-4","DOIUrl":"https://doi.org/10.1038/s41408-026-01464-4","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"226 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147381242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cytogenetic and genomic profiling of acute myeloid leukemia (AML) guides personalized treatment according to ELN2022 recommendations. However, marked outcome variability persists among cytogenetically normal (CN-) patients, representing an unmet clinical need. We used long-read whole-genome sequencing to interrogate the prognostic significance of structural variations (SVs) in a prospective cohort of 162 intensively treated CN-AML patients. After stringent filtering, we identified 5 somatic SVs associated with shorter overall survival (OS) (HR:4.18, p < 0.001) and event-free survival (EFS) (HR:3.59, p < 0.001) in 13% of the patients. Results were validated in a real-world cohort of 149 CN-AML, using target assays. These high-risk SVs (HRVs) operationally defined a "very high-risk" category in the framework of ELN2022, overall resulting in more accurate OS prediction. HRVs were independent of most frequent mutations, particularly FLT3ITD and NPM1mut. Among the latter patients, HRVs independently predicted shorter OS (8.2 months versus not-reached; p < 0.001), EFS (3.5 versus 25.7 months; p < 0.001), and lower complete response rates (66.7% versus 90.1%; p < 0.005). Finally, we provided evidence of transcriptional deregulation of SV-related genes in primary samples and engineered cell models. Current findings support the value of SVs for refining risk stratification in CN-AML, by identifying patients at exceedingly dismal outcome who might benefit from personalized approaches.
根据ELN2022的建议，急性髓性白血病（AML）的细胞遗传学和基因组图谱指导个性化治疗。然而，在细胞遗传学正常（CN-）患者中，显著的结果变异性仍然存在，这代表了未满足的临床需求。我们使用长读全基因组测序在162名密集治疗的CN-AML患者的前瞻性队列中询问结构变异（SVs）的预后意义。经过严格的筛选，我们在13%的患者中确定了5个与较短的总生存期（OS） （HR:4.18, p < 0.001）和无事件生存期（EFS） （HR:3.59, p < 0.001）相关的体细胞SVs。结果在149例CN-AML的现实世界队列中得到验证，使用靶标测定。在ELN2022框架中，这些高风险svv （hrv）在操作上定义了一个“非常高风险”的类别，总体上导致更准确的OS预测。hrv独立于最常见的突变，特别是FLT3ITD和NPM1mut。在后者患者中，hrv独立预测更短的OS(8.2个月vs未达到，p < 0.001)， EFS（3.5个月vs 25.7个月，p < 0.001）和更低的完全缓解率（66.7% vs 90.1%, p < 0.005）。最后，我们在原代样品和工程细胞模型中提供了svv相关基因转录失调的证据。目前的研究结果支持SVs在CN-AML中细化风险分层的价值，通过识别可能从个性化方法中获益的预后非常糟糕的患者。
{"title":"Genomic structural variations contribute to inform prognosis in patients with cytogenetically normal acute myeloid leukemia.","authors":"Niccolò Bartalucci,Francesco Mannelli,Danilo Tarantino,Alessio Enderti,Simone Romagnoli,Daniele Colazzo,Barbara Scappini,Giacomo Gianfaldoni,Matteo Piccini,Leonardo Signori,Fiorenza Irushani,Silvia Salmoiraghi,Tiziana Ottone,Alfonso Piciocchi,Margherita Vannucchi,Maria Chiara Siciliano,Roberto Boccacci,Silvia Orsi,Alessia Civini,Paola Fazi,Raffaella Santi,Marco Vignetti,Stefania Bortoluzzi,Alberto Bosi,Adriano Venditti,Alessandro Rambaldi,Maria Teresa Voso,Paola Guglielmelli,Alessandro M Vannucchi","doi":"10.1038/s41408-026-01465-3","DOIUrl":"https://doi.org/10.1038/s41408-026-01465-3","url":null,"abstract":"Cytogenetic and genomic profiling of acute myeloid leukemia (AML) guides personalized treatment according to ELN2022 recommendations. However, marked outcome variability persists among cytogenetically normal (CN-) patients, representing an unmet clinical need. We used long-read whole-genome sequencing to interrogate the prognostic significance of structural variations (SVs) in a prospective cohort of 162 intensively treated CN-AML patients. After stringent filtering, we identified 5 somatic SVs associated with shorter overall survival (OS) (HR:4.18, p < 0.001) and event-free survival (EFS) (HR:3.59, p < 0.001) in 13% of the patients. Results were validated in a real-world cohort of 149 CN-AML, using target assays. These high-risk SVs (HRVs) operationally defined a \"very high-risk\" category in the framework of ELN2022, overall resulting in more accurate OS prediction. HRVs were independent of most frequent mutations, particularly FLT3ITD and NPM1mut. Among the latter patients, HRVs independently predicted shorter OS (8.2 months versus not-reached; p < 0.001), EFS (3.5 versus 25.7 months; p < 0.001), and lower complete response rates (66.7% versus 90.1%; p < 0.005). Finally, we provided evidence of transcriptional deregulation of SV-related genes in primary samples and engineered cell models. Current findings support the value of SVs for refining risk stratification in CN-AML, by identifying patients at exceedingly dismal outcome who might benefit from personalized approaches.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"4 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147368371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-21DOI: 10.1038/s41408-026-01451-9
Febe Smits, Kaz Groen, Charlotte L B M Korst, Kris A Frerichs, Ilse Kuipers, Sandy Kruyswijk, Maaike E M de Ruijter, Kazem Nasserinejad, Sonja Zweegman, Niels W C J van de Donk
Patients with relapsed/refractory multiple myeloma (RRMM) who are treated with BCMA-directed bispecific antibodies (BsAbs) are at an increased risk for infections. Previous studies have shown that treatment with intravenous immunoglobulin (IVIG) reduced the risk for severe infections. However, whether IVIG also reduces all-grade infections and whether there is an impact of longer dosing intervals on infection risk remains unknown. To address this, we retrospectively investigated 80 patients with RRMM who were treated with teclistamab in a single center. After a median follow-up of 21 months, in total 390 infections were reported, of which 48 were severe. Treatment with IVIG resulted in significantly lower rates of both severe infections (0.33 vs. 0.93 per patient-year) as well as of all-grade infections (3.15 vs. 4.41 per patient-year). Multivariable analyses revealed that older age and higher beta-2-microglobulin levels were associated with an increased risk of severe breakthrough infections during IVIG supplementation. Importantly, longer dosing intervals reduced infection rates for all-grade infections (from 6.08 infections per patient-year during weekly dosing to 2.25 infections per patient-year during bimonthly dosing) and for severe infections (from 0.81 infections per patient-year during weekly dosing to 0.1 per patient-year during bimonthly dosing). These results underline the importance of the assessment of annualized infection rates to reflect the true infectious burden in patients who were treated with BCMA-directed BsAbs.
接受bcma定向双特异性抗体（BsAbs）治疗的复发/难治性多发性骨髓瘤（RRMM）患者感染风险增加。先前的研究表明，静脉注射免疫球蛋白（IVIG）治疗降低了严重感染的风险。然而，IVIG是否也能减少所有级别的感染，以及较长的给药间隔是否对感染风险有影响仍然未知。为了解决这个问题，我们回顾性调查了80例在单中心接受teclistamab治疗的RRMM患者。在中位随访21个月后，总共报告了390例感染，其中48例为严重感染。IVIG治疗导致严重感染（0.33 vs 0.93 /患者-年）和所有级别感染（3.15 vs 4.41 /患者-年）的发生率显著降低。多变量分析显示，年龄越大和β -2微球蛋白水平越高与补充IVIG期间严重突破性感染的风险增加有关。重要的是，较长的给药间隔降低了所有级别感染的感染率（从每周给药期间的6.08例感染/患者年降至双月给药期间的2.25例感染/患者年）和严重感染（从每周给药期间的0.81例感染/患者年降至双月给药期间的0.1例感染/患者年）。这些结果强调了评估年化感染率的重要性，以反映接受bcma定向bsab治疗的患者的真实感染负担。
{"title":"Immunoglobulin supplementation and longer dosing intervals reduce risk of infections in patients with RRMM treated with teclistamab.","authors":"Febe Smits, Kaz Groen, Charlotte L B M Korst, Kris A Frerichs, Ilse Kuipers, Sandy Kruyswijk, Maaike E M de Ruijter, Kazem Nasserinejad, Sonja Zweegman, Niels W C J van de Donk","doi":"10.1038/s41408-026-01451-9","DOIUrl":"10.1038/s41408-026-01451-9","url":null,"abstract":"<p><p>Patients with relapsed/refractory multiple myeloma (RRMM) who are treated with BCMA-directed bispecific antibodies (BsAbs) are at an increased risk for infections. Previous studies have shown that treatment with intravenous immunoglobulin (IVIG) reduced the risk for severe infections. However, whether IVIG also reduces all-grade infections and whether there is an impact of longer dosing intervals on infection risk remains unknown. To address this, we retrospectively investigated 80 patients with RRMM who were treated with teclistamab in a single center. After a median follow-up of 21 months, in total 390 infections were reported, of which 48 were severe. Treatment with IVIG resulted in significantly lower rates of both severe infections (0.33 vs. 0.93 per patient-year) as well as of all-grade infections (3.15 vs. 4.41 per patient-year). Multivariable analyses revealed that older age and higher beta-2-microglobulin levels were associated with an increased risk of severe breakthrough infections during IVIG supplementation. Importantly, longer dosing intervals reduced infection rates for all-grade infections (from 6.08 infections per patient-year during weekly dosing to 2.25 infections per patient-year during bimonthly dosing) and for severe infections (from 0.81 infections per patient-year during weekly dosing to 0.1 per patient-year during bimonthly dosing). These results underline the importance of the assessment of annualized infection rates to reflect the true infectious burden in patients who were treated with BCMA-directed BsAbs.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12960722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146257383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This clinical trial (NCT05347641) evaluated efficacy and safety of penpulimab combined with rituximab, high-dose methotrexate, and cytarabine (Pen-RMA) in patients with newly diagnosed (ND) primary central nervous system lymphoma (PCNSL). Patients received an induction treatment of six cycles of Pen-RMA every 3 weeks. Patients younger than 60 years who achieved at least partial remission (PR) underwent autologous stem cell transplantation (ASCT), followed by 8 cycles of penpulimab as maintenance therapy. For patients over 60 years or not eligible for ASCT who achieved complete remission (CR) after induction therapy received 8 cycles of penpulimab as maintenance treatment, and those who achieved PR were treated with whole brain radiotherapy (WBRT) combined with 8 cycles of penpulimab. Patients who achieved stable disease (SD) or progressive disease (PD) were withdrawn from this study. The primary endpoint was 2-year progression-free survival (PFS). Between April 2022 and December 2023, twenty-six ND-PCNSL patients were enrolled, and 23 patients were included in the intention-to-treat analysis. The median age was 65 (38‒74) yr. The overall response rate (ORR) and CR rate after the induction therapy were 95.7% and 91.3%, respectively. At a median follow-up of 29.4 months, the median PFS and overall survival (OS) were not reached. 2-year PFS and OS were 70.7% and 75.0%, respectively. The most frequent treatment-related adverse events were leukopenia, anemia, neutropenia, and thrombocytopenia. Grade 3 or worse treatment-related adverse events occurred in 7 (30.4%) of 23 patients. Cerebrospinal fluid (CSF) circulating-tumor DNA (ctDNA) monitoring was performed in 13 patients with imaging CR and 1 with PR after induction treatment. Among them, 8 had CSF ctDNA clearance while 6 were positive. Overall, Pen-RMA regimen demonstrated encouraging antitumor activity with a manageable toxicity in PCNSL.
{"title":"Penpulimab combined with rituximab, high-dose methotrexate, and cytarabine (Pen-RMA) in newly diagnosed primary central nervous system lymphoma (PCNSL): a phase 2 trial","authors":"Hao-Rui Shen, Jia-Zhu Wu, Hua Yin, Kai-Xin Du, Luthuli Sibusiso, Yi-Fan Wu, Wei Hua, Yue Li, Yi-Lin Kong, Xin-Yu Zhang, Rui Gao, Jian-Yong Li, Li Wang, Jin-Hua Liang, Wei Xu","doi":"10.1038/s41408-026-01450-w","DOIUrl":"https://doi.org/10.1038/s41408-026-01450-w","url":null,"abstract":"This clinical trial (NCT05347641) evaluated efficacy and safety of penpulimab combined with rituximab, high-dose methotrexate, and cytarabine (Pen-RMA) in patients with newly diagnosed (ND) primary central nervous system lymphoma (PCNSL). Patients received an induction treatment of six cycles of Pen-RMA every 3 weeks. Patients younger than 60 years who achieved at least partial remission (PR) underwent autologous stem cell transplantation (ASCT), followed by 8 cycles of penpulimab as maintenance therapy. For patients over 60 years or not eligible for ASCT who achieved complete remission (CR) after induction therapy received 8 cycles of penpulimab as maintenance treatment, and those who achieved PR were treated with whole brain radiotherapy (WBRT) combined with 8 cycles of penpulimab. Patients who achieved stable disease (SD) or progressive disease (PD) were withdrawn from this study. The primary endpoint was 2-year progression-free survival (PFS). Between April 2022 and December 2023, twenty-six ND-PCNSL patients were enrolled, and 23 patients were included in the intention-to-treat analysis. The median age was 65 (38‒74) yr. The overall response rate (ORR) and CR rate after the induction therapy were 95.7% and 91.3%, respectively. At a median follow-up of 29.4 months, the median PFS and overall survival (OS) were not reached. 2-year PFS and OS were 70.7% and 75.0%, respectively. The most frequent treatment-related adverse events were leukopenia, anemia, neutropenia, and thrombocytopenia. Grade 3 or worse treatment-related adverse events occurred in 7 (30.4%) of 23 patients. Cerebrospinal fluid (CSF) circulating-tumor DNA (ctDNA) monitoring was performed in 13 patients with imaging CR and 1 with PR after induction treatment. Among them, 8 had CSF ctDNA clearance while 6 were positive. Overall, Pen-RMA regimen demonstrated encouraging antitumor activity with a manageable toxicity in PCNSL.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"46 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146152301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-28DOI: 10.1038/s41408-025-01432-4
Eva Domingo-Domènech, Barbara Pro, Tim Illidge, Steven Horwitz, Lorenz Trumper, Swami Iyer, Ranjana Advani, Nancy L. Bartlett, Jacob Haaber Christensen, Won-Seog Kim, Tatyana Feldman, Ilseung Choi, Giuseppe Gritti, David Belada, Andrei Shustov, Arpad Illes, Pier Luigi Zinzani, Andreas Hüttmann, Marek Trneny, Steven Le Gouill, Deepa Jagadeesh, Jonathan W. Friedberg, Meredith Little, Cassie Dong, Michelle Fanale, Keenan Fenton, Kerry J. Savage
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