Despite allo-HSCT being the primary curative treatment for high-risk AML, relapse-free survival (RFS) remains suboptimal due to high relapse incidence. Our research focuses on optimizing the conditioning regimen by incorporating Mitoxantrone Hydrochloride Liposome (Lipo-MIT), a novel nano-formulation with enhanced pharmacokinetic properties and demonstrated anti-leukemic efficacy. Preclinical studies have shown that Lipo-MIT significantly improves survival outcomes compared to conventional mitoxantrone, and our study aims to translate these findings into clinical practice. In this study, we present the results of a Lipo-MIT as part of the conditioning regimen for high-risk AML patients undergoing allo-HSCT. Our findings highlight the potential of Lipo-MIT to improve RFS, while also providing insights into patient selection and the refinement of Lipo-MIT-based conditioning strategies. We believe this work contributes valuable knowledge to the field and has the potential to impact clinical practice.
{"title":"The Efficacy and Safety of the Addition of Mitoxantrone Hydrochloride Liposome in Conditioning Regimen for High-Risk Acute Myeloid Leukemia","authors":"Xiaoyu Zhang, Donglin Yang, Aiming Pang, Sizhou Feng, Mingzhe Han, Yi He, Erlie Jiang","doi":"10.1002/hon.70116","DOIUrl":"https://doi.org/10.1002/hon.70116","url":null,"abstract":"<p>Despite allo-HSCT being the primary curative treatment for high-risk AML, relapse-free survival (RFS) remains suboptimal due to high relapse incidence. Our research focuses on optimizing the conditioning regimen by incorporating Mitoxantrone Hydrochloride Liposome (Lipo-MIT), a novel nano-formulation with enhanced pharmacokinetic properties and demonstrated anti-leukemic efficacy. Preclinical studies have shown that Lipo-MIT significantly improves survival outcomes compared to conventional mitoxantrone, and our study aims to translate these findings into clinical practice. In this study, we present the results of a Lipo-MIT as part of the conditioning regimen for high-risk AML patients undergoing allo-HSCT. Our findings highlight the potential of Lipo-MIT to improve RFS, while also providing insights into patient selection and the refinement of Lipo-MIT-based conditioning strategies. We believe this work contributes valuable knowledge to the field and has the potential to impact clinical practice.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144550835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
An exploratory analysis of past clinical trials was conducted to propose a predictive scoring system for the efficacy of mogamulizumab, an anti-CC chemokine receptor 4 (CCR4) antibody, based on easily measurable parameters. Factors affecting progression-free survival (PFS) were investigated using data from three clinical trials (NCT00920790, NCT01626664, and NCT01173887) and one clinical study (UMIN000013294) conducted in patients with relapsed/refractory (R/R) or untreated CCR4-positive aggressive adult T-cell leukemia-lymphoma (ATL) receiving mogamulizumab treatment. Twelve routinely measured clinical parameters and three calculated indices—lymphocyte-to-neutrophil count ratio, platelet-to-lymphocyte count ratio, and lymphocyte-to-monocyte count ratio (LMR)—were selected as variables. Univariate Cox proportional hazards analysis identified albumin level, disease type, lactate dehydrogenase (LDH), monocyte count, neutrophil count, and LMR as relevant factors in R/R ATL patients treated with mogamulizumab monotherapy (p < 0.05). A predictive model constructed from multivariate analysis results stratified the monotherapy group (n = 69) into three subgroups, with scores of 0 (n = 5), 1 (n = 25), and 2 (n = 39), based on LDH (0 for < 265 and 1 for ≥ 265) and LMR (0 for ≥ 3.571 and 1 for < 3.571). Median PFS values were 0.57, 0.46, and 0.07 years for scores 0, 1, and 2, respectively (log-rank test: p = 0.005 for score 0 vs. 2; p < 0.001 for score 1 vs. 2). The simple model combining LDH and LMR may predict PFS in patients with R/R aggressive ATL receiving mogamulizumab treatment. Since LDH and LMR are easily measurable in clinical practice, this model could help predict mogamulizumab efficacy and guide treatment decisions in this patient population.
Trial Registration: Registration number: UMIN000049135. Date of registration: October 17, 2022
{"title":"Exploratory Analysis of Practical Predictive Indices for the Efficacy of Mogamulizumab in Patients With Aggressive Adult T-Cell Leukemia-Lymphoma","authors":"Yutaka Shimazu, Kenta Murotani, Hiroki Kitabayashi, Yukihiro Nishio","doi":"10.1002/hon.70114","DOIUrl":"https://doi.org/10.1002/hon.70114","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>An exploratory analysis of past clinical trials was conducted to propose a predictive scoring system for the efficacy of mogamulizumab, an anti-CC chemokine receptor 4 (CCR4) antibody, based on easily measurable parameters. Factors affecting progression-free survival (PFS) were investigated using data from three clinical trials (NCT00920790, NCT01626664, and NCT01173887) and one clinical study (UMIN000013294) conducted in patients with relapsed/refractory (R/R) or untreated CCR4-positive aggressive adult T-cell leukemia-lymphoma (ATL) receiving mogamulizumab treatment. Twelve routinely measured clinical parameters and three calculated indices—lymphocyte-to-neutrophil count ratio, platelet-to-lymphocyte count ratio, and lymphocyte-to-monocyte count ratio (LMR)—were selected as variables. Univariate Cox proportional hazards analysis identified albumin level, disease type, lactate dehydrogenase (LDH), monocyte count, neutrophil count, and LMR as relevant factors in R/R ATL patients treated with mogamulizumab monotherapy (<i>p</i> < 0.05). A predictive model constructed from multivariate analysis results stratified the monotherapy group (<i>n</i> = 69) into three subgroups, with scores of 0 (<i>n</i> = 5), 1 (<i>n</i> = 25), and 2 (<i>n</i> = 39), based on LDH (0 for < 265 and 1 for ≥ 265) and LMR (0 for ≥ 3.571 and 1 for < 3.571). Median PFS values were 0.57, 0.46, and 0.07 years for scores 0, 1, and 2, respectively (log-rank test: <i>p</i> = 0.005 for score 0 vs. 2; <i>p</i> < 0.001 for score 1 vs. 2). The simple model combining LDH and LMR may predict PFS in patients with R/R aggressive ATL receiving mogamulizumab treatment. Since LDH and LMR are easily measurable in clinical practice, this model could help predict mogamulizumab efficacy and guide treatment decisions in this patient population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <p><b>Trial Registration:</b> Registration number: UMIN000049135. Date of registration: October 17, 2022</p>\u0000 </section>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xinyao Liu, Danchen Meng, Yuxin Li, Min Ruan, Zhenqi Huang, Wei Wu, Jian Ge, Jichun Yang, Zhangbiao Long
Low-dose venetoclax plus strong CYP3A4 inhibitor voriconazole were commonly used for acute myeloid leukemia (AML) patients who were unfit for intensive chemotherapy in China. However, the efficacy and safety of this schedule have not been well investigated. We analyzed clinical data from 54 patients with a median age of 67 years. Thirty patients received a standard dose of venetoclax plus azacitidine (cohort 1), whereas another 24 patients received low-dose venetoclax plus voriconazole plus azacitidine (cohort 2). The composite complete remission (complete remission or complete remission with incomplete hematologic recovery; CR/CRi) rate was 76.7% (23/30) in cohort 1 and 87.5% (21/24) in cohort 2 (p = 0.483). At a median follow-up of 16 months, the median progression-free survival was 12 months in cohort 1 and 18 months in cohort 2 (p = 0.241). The median overall survival was 14 months in cohort 1 and 19 months in cohort 2 (p = 0.453). Key adverse events included cytopenia and infections. Grade 3 or higher infections occurred in 36.7% of the patients in cohort 1 and 20.8% of those in cohort 2. In conclusion, this study demonstrated the safety and effectiveness of the combination of low-dose venetoclax and voriconazole in unfit AML.
{"title":"Safety and Efficacy of Low-Dose Venetoclax Plus Voriconazole in Patients With Acute Myeloid Leukemia Unfit for Intensive Chemotherapy","authors":"Xinyao Liu, Danchen Meng, Yuxin Li, Min Ruan, Zhenqi Huang, Wei Wu, Jian Ge, Jichun Yang, Zhangbiao Long","doi":"10.1002/hon.70113","DOIUrl":"https://doi.org/10.1002/hon.70113","url":null,"abstract":"<div>\u0000 \u0000 <p>Low-dose venetoclax plus strong CYP3A4 inhibitor voriconazole were commonly used for acute myeloid leukemia (AML) patients who were unfit for intensive chemotherapy in China. However, the efficacy and safety of this schedule have not been well investigated. We analyzed clinical data from 54 patients with a median age of 67 years. Thirty patients received a standard dose of venetoclax plus azacitidine (cohort 1), whereas another 24 patients received low-dose venetoclax plus voriconazole plus azacitidine (cohort 2). The composite complete remission (complete remission or complete remission with incomplete hematologic recovery; CR/CRi) rate was 76.7% (23/30) in cohort 1 and 87.5% (21/24) in cohort 2 (<i>p</i> = 0.483). At a median follow-up of 16 months, the median progression-free survival was 12 months in cohort 1 and 18 months in cohort 2 (<i>p</i> = 0.241). The median overall survival was 14 months in cohort 1 and 19 months in cohort 2 (<i>p</i> = 0.453). Key adverse events included cytopenia and infections. Grade 3 or higher infections occurred in 36.7% of the patients in cohort 1 and 20.8% of those in cohort 2. In conclusion, this study demonstrated the safety and effectiveness of the combination of low-dose venetoclax and voriconazole in unfit AML.</p>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503281","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}
Dong Liang, Yurong Yan, Qiaoli Wang, Shenrui Bai, Weiling Xu, Demei Feng, Yuying Bu, Min Zeng, Xiaomiao Nie, Yuan Feng, Xiaoqin Chen, Zhongjun Xia, Yang Liang, Fengyan Jin, Hua Wang
This study aimed to discuss the clinical outcomes of extramedullary multiple myeloma in the era of novel agents, based on the largest dataset regarding extramedullary multiple myeloma in China. This study included 597 patients without extramedullary disease (EMD) (non-EMD), 324 with extramedullary bone-related disease (EMB) and 138 with de novo extramedullary extraosseous disease (EME). There were no significant differences in overall survival (OS, p = 0.638) or progression-free survival (PFS, p = 0.195) between non-EMD and EMB patients. However, de novo EME patients exhibited significantly worse OS (p < 0.01) and PFS (p < 0.01) compared to both EMB and non-EMD groups. Among non-EMD and EMB patients, those with ≥ 2 high-risk cytogenetic abnormalities (HRA) experienced extremely poor prognoses, categorizing them as ultra-high-risk multiple myeloma. Similarly, de novo EME patients with ≥ 1 HRA demonstrated very poor outcomes and should also be considered ultra-high risk. Notably, single transplantation was shown to mitigate the adverse prognosis of de novo EME patients. Furthermore, the daratumumab bortezomib lenalidomide dexamethasone (DVRD) quadruplet regimen showed potential as effective frontline therapies for de novo EME patients, offering hope for improved treatment outcomes in this challenging subgroup. These findings suggest that de novo EME represents an extremely poor prognosis and should be treated as a distinct entity within the multiple myeloma population. Furthermore, the results indicate that EMB may need to be excluded from the current EMD definition to better delineate these subgroups and guide therapeutic strategies.
本研究基于国内最大的髓外多发性骨髓瘤数据集，旨在探讨新型药物时代髓外多发性骨髓瘤的临床结局。本研究纳入597例无髓外疾病（EMD）（非EMD）， 324例髓外骨相关疾病（EMB）和138例新发髓外骨外疾病（EME）患者。非emd和EMB患者的总生存期（OS, p = 0.638）和无进展生存期（PFS, p = 0.195）无显著差异。然而，新发EME患者的OS明显较差(p <；0.01)和PFS (p <；0.01)，与EMB组和非emd组比较。在非emd和EMB患者中，≥2例高危细胞遗传学异常（HRA）的患者预后极差，归类为超高危多发性骨髓瘤。同样，HRA≥1的新发EME患者表现出非常差的预后，也应考虑为超高风险。值得注意的是，单次移植被证明可以减轻新发EME患者的不良预后。此外，达拉单抗硼替佐米来那度胺地塞米松（DVRD）四组方案显示出作为新发EME患者有效一线治疗的潜力，为改善这一具有挑战性的亚组的治疗结果提供了希望。这些研究结果表明，新生EME预后极差，应作为多发性骨髓瘤人群中的一个独特实体来治疗。此外，研究结果表明，EMB可能需要从当前的EMD定义中排除，以更好地描述这些亚组并指导治疗策略。
{"title":"Clinical Outcome of Extramedullary Multiple Myeloma in the Era of Novel Agents: Insights From a Multicenter Study","authors":"Dong Liang, Yurong Yan, Qiaoli Wang, Shenrui Bai, Weiling Xu, Demei Feng, Yuying Bu, Min Zeng, Xiaomiao Nie, Yuan Feng, Xiaoqin Chen, Zhongjun Xia, Yang Liang, Fengyan Jin, Hua Wang","doi":"10.1002/hon.70112","DOIUrl":"https://doi.org/10.1002/hon.70112","url":null,"abstract":"<div>\u0000 \u0000 <p>This study aimed to discuss the clinical outcomes of extramedullary multiple myeloma in the era of novel agents, based on the largest dataset regarding extramedullary multiple myeloma in China. This study included 597 patients without extramedullary disease (EMD) (non-EMD), 324 with extramedullary bone-related disease (EMB) and 138 with de novo extramedullary extraosseous disease (EME). There were no significant differences in overall survival (OS, <i>p</i> = 0.638) or progression-free survival (PFS, <i>p</i> = 0.195) between non-EMD and EMB patients. However, de novo EME patients exhibited significantly worse OS (<i>p</i> < 0.01) and PFS (<i>p</i> < 0.01) compared to both EMB and non-EMD groups. Among non-EMD and EMB patients, those with ≥ 2 high-risk cytogenetic abnormalities (HRA) experienced extremely poor prognoses, categorizing them as ultra-high-risk multiple myeloma. Similarly, de novo EME patients with ≥ 1 HRA demonstrated very poor outcomes and should also be considered ultra-high risk. Notably, single transplantation was shown to mitigate the adverse prognosis of de novo EME patients. Furthermore, the daratumumab bortezomib lenalidomide dexamethasone (DVRD) quadruplet regimen showed potential as effective frontline therapies for de novo EME patients, offering hope for improved treatment outcomes in this challenging subgroup. These findings suggest that de novo EME represents an extremely poor prognosis and should be treated as a distinct entity within the multiple myeloma population. Furthermore, the results indicate that EMB may need to be excluded from the current EMD definition to better delineate these subgroups and guide therapeutic strategies.</p>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339313","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}
Annarita Conconi, Andrea Janikova, Barbara Vannata, Ana Florencia Ramírez-Ibarguen, Chiara Lobetti-Bodoni, David Belada, Maria Cristina Pirosa, Michael Mian, Andrés J. M. Ferreri, Gail Ryan, Gerassimos Pangalis, Maria Elena Cabrera, Stefano Luminari, Silvia Montoto, Richard Tsang, Igor Aurer, Carlo Visco, Gloria Margiotta Casaluci, Vit Prochazka, Samuel Hricko, Anastasios Stathis, Luca Mazzucchelli, Maurilio Ponzoni, Massimo Federico, Gianluca Gaidano, Armando Lopez-Guillermo, Barbara Pro, Davide Rossi, Luciano Cascione, Grzegorz Nowakowsky, Marek Trneny, Emanuele Zucca
The characteristics at diagnosis and clinical course of primary extranodal follicular lymphoma (EFL) have not been extensively described. The International Extranodal Lymphoma Study Group (IELSG) conducted an international retrospective survey aimed to describe the clinical features at diagnosis and the outcomes of FL cases with a clinically dominant extranodal component. The dataset included 605 pathologically reviewed cases from 19 different countries, and their outcomes were compared to those of nodal follicular lymphomas. The two most common presentation sites for EFL were the skin (n = 334) and the gastrointestinal tract (n = 72), with 22 cases having primary duodenal localization. These subsets exhibited unique features at diagnosis and significantly different overall survival (OS) patterns. After a median follow-up of 5.5 years, primary cutaneous lymphomas showed a superior outcome [10-year OS: 89% (95% CI, 83%–93%)], while primary gastrointestinal lymphomas had an intermediate outcome [10-year OS: 79% (95% CI, 59%–90%)]. Among the gastrointestinal lymphomas, primary duodenal lymphomas tended toward the best outcome [10-year OS: 95% (95% CI, 69%–99%)]. Other primary extranodal sites had inferior outcomes [10-year OS: 59% (95% CI, 48%–68%)], similar to primary nodal lymphomas [10-year OS: 57% (95% CI, 49%–64%)]. These findings support the identification of specific primary FL localizations as distinct entities with particular clinical and biological characteristics.
{"title":"Primary Extranodal Follicular Lymphoma: A Retrospective Survey of the International Extranodal Lymphoma Study Group (IELSG)","authors":"Annarita Conconi, Andrea Janikova, Barbara Vannata, Ana Florencia Ramírez-Ibarguen, Chiara Lobetti-Bodoni, David Belada, Maria Cristina Pirosa, Michael Mian, Andrés J. M. Ferreri, Gail Ryan, Gerassimos Pangalis, Maria Elena Cabrera, Stefano Luminari, Silvia Montoto, Richard Tsang, Igor Aurer, Carlo Visco, Gloria Margiotta Casaluci, Vit Prochazka, Samuel Hricko, Anastasios Stathis, Luca Mazzucchelli, Maurilio Ponzoni, Massimo Federico, Gianluca Gaidano, Armando Lopez-Guillermo, Barbara Pro, Davide Rossi, Luciano Cascione, Grzegorz Nowakowsky, Marek Trneny, Emanuele Zucca","doi":"10.1002/hon.70111","DOIUrl":"https://doi.org/10.1002/hon.70111","url":null,"abstract":"<div>\u0000 \u0000 <p>The characteristics at diagnosis and clinical course of primary extranodal follicular lymphoma (EFL) have not been extensively described. The International Extranodal Lymphoma Study Group (IELSG) conducted an international retrospective survey aimed to describe the clinical features at diagnosis and the outcomes of FL cases with a clinically dominant extranodal component. The dataset included 605 pathologically reviewed cases from 19 different countries, and their outcomes were compared to those of nodal follicular lymphomas. The two most common presentation sites for EFL were the skin (<i>n</i> = 334) and the gastrointestinal tract (<i>n</i> = 72), with 22 cases having primary duodenal localization. These subsets exhibited unique features at diagnosis and significantly different overall survival (OS) patterns. After a median follow-up of 5.5 years, primary cutaneous lymphomas showed a superior outcome [10-year OS: 89% (95% CI, 83%–93%)], while primary gastrointestinal lymphomas had an intermediate outcome [10-year OS: 79% (95% CI, 59%–90%)]. Among the gastrointestinal lymphomas, primary duodenal lymphomas tended toward the best outcome [10-year OS: 95% (95% CI, 69%–99%)]. Other primary extranodal sites had inferior outcomes [10-year OS: 59% (95% CI, 48%–68%)], similar to primary nodal lymphomas [10-year OS: 57% (95% CI, 49%–64%)]. These findings support the identification of specific primary FL localizations as distinct entities with particular clinical and biological characteristics.</p>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339133","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}
P. Barr, P. Ghia, D. Rossi, E. Ferrant, F. De la Cruz Vicente, D. Maruyama, V. Banerji, P. Cobb, S. Namburi, R. Greil, A. Loubert, K. Creel, L. M. Hess, N. Payakachat, A. S. Ruppert, D. Wang, P. Abada, C. C. Leow, M. Hill, C. C. Coombs, J. P. Sharman
<p><b>Introduction:</b> The phase 3, randomized trial BRUIN CLL-321 assessed the safety and efficacy of pirtobrutinib compared to investigators choice (IC) of idelalisib plus rituximab (IdelaR) or bendamustine + rituximab (BR) in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) previously treated with a covalent BTK inhibitor (cBTKi). BRUIN CLL-321 showed significantly improved progression-free survival and longer time to next treatment or death with pirtobrutinib compared to IdealR/BR. Exploratory endpoints of the trial assessed changes from baseline in patient reported outcomes (PROs) through week 25 for patients treated with pirtobrutinib compared to IdelaR/BR.</p><p><b>Methods:</b> Patients with relapsed/refractory CLL/SLL, who received at least one prior cBTKi, were enrolled in BRUIN CLL-321. Endpoints included the evaluation of PROs between groups, as measured by three tools: the EORTC QLQ-C30 physical function (PF) scale, a CLL/SLL-related symptoms scale, and a fatigue scale expanded from the QLQ-C30 fatigue scale. PROs were collected every 4 weeks during study treatment. A positive least square means difference (LSM<sub>d</sub>) PF score reflected PF improvement from baseline in the pirtobrutinib group, while a negative change in symptoms or fatigue LSM<sub>d</sub> reflected improvement in the pirtobrutinib group from baseline compared to IdelaR/BR. Longitudinal analyses used mixed model for repeated measures adjusted for baseline PRO scores. Thresholds for clinically meaningful between-group differences were defined a priori from Cocks et al. (<i>JCO</i> 29 (1):89–96, 2011). The statistical testing of PRO endpoints was not type-1 error controlled and thus descriptive in nature.</p><p><b>Results:</b> A total of 119 patients were randomized to each treatment arm (<i>N</i> = 238). PRO completion rate was 82.1% at baseline and remained above 80% at each subsequent assessment through Week 25. CLL/SLL-related symptoms were clinically meaningfully lower in the pirtobrutinib group versus IdelaR/BR at Week 9 (LSM<sub>d</sub>, −7.3 [standard error (SE), 2.2]), Week 13 (LSM<sub>d</sub>, −6.7 [SE, 2.3]), Week 17 (LSM<sub>d</sub>, −4.6 [SE, 2.3]), and Week 21 (LSM<sub>d</sub>, −7.0 [SE, 2.3]). Patients in the pirtobrutinib group reported lower fatigue scores versus those receiving IdelaR/BR at Week 9 (LSM<sub>d</sub>, −9.0 [SE, 2.9]), Week 13 (LSM<sub>d</sub>, −6.7 [SE, 3.0]), and Week 21 (LSM<sub>d</sub>, −6.9 [SE, 3.1]). Patients in the pirtobrutinib group also reported better PF versus IdelaR/BR at Weeks 13 (LSM<sub>d</sub>, 5.6 [SE, 2.4]) and 21 (LSM<sub>d</sub>, 5.9 [SE, 2.5]).</p><p><b>Conclusions:</b> These analyses suggest a meaningful and clinically relevant improvement in CLL/SLL-related symptoms, physical functioning, and fatigue at most assessments between baseline and Week 25 in the pirtobrutinib group compared to IdelaR/BR. Most PRO assessments met clinically meaningful thresholds, and for those that did n
{"title":"PATIENT REPORTED OUTCOMES FROM BRUIN CLL-321: PHASE 3 TRIAL COMPARING PIRTOBRUTINIB TO IDELALISIB/RITUXIMAB OR BENDAMUSTINE/RITUXIMAB IN COVALENT BTKi PRETREATED CLL/SLL","authors":"P. Barr, P. Ghia, D. Rossi, E. Ferrant, F. De la Cruz Vicente, D. Maruyama, V. Banerji, P. Cobb, S. Namburi, R. Greil, A. Loubert, K. Creel, L. M. Hess, N. Payakachat, A. S. Ruppert, D. Wang, P. Abada, C. C. Leow, M. Hill, C. C. Coombs, J. P. Sharman","doi":"10.1002/hon.70094_219","DOIUrl":"https://doi.org/10.1002/hon.70094_219","url":null,"abstract":"<p><b>Introduction:</b> The phase 3, randomized trial BRUIN CLL-321 assessed the safety and efficacy of pirtobrutinib compared to investigators choice (IC) of idelalisib plus rituximab (IdelaR) or bendamustine + rituximab (BR) in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) previously treated with a covalent BTK inhibitor (cBTKi). BRUIN CLL-321 showed significantly improved progression-free survival and longer time to next treatment or death with pirtobrutinib compared to IdealR/BR. Exploratory endpoints of the trial assessed changes from baseline in patient reported outcomes (PROs) through week 25 for patients treated with pirtobrutinib compared to IdelaR/BR.</p><p><b>Methods:</b> Patients with relapsed/refractory CLL/SLL, who received at least one prior cBTKi, were enrolled in BRUIN CLL-321. Endpoints included the evaluation of PROs between groups, as measured by three tools: the EORTC QLQ-C30 physical function (PF) scale, a CLL/SLL-related symptoms scale, and a fatigue scale expanded from the QLQ-C30 fatigue scale. PROs were collected every 4 weeks during study treatment. A positive least square means difference (LSM<sub>d</sub>) PF score reflected PF improvement from baseline in the pirtobrutinib group, while a negative change in symptoms or fatigue LSM<sub>d</sub> reflected improvement in the pirtobrutinib group from baseline compared to IdelaR/BR. Longitudinal analyses used mixed model for repeated measures adjusted for baseline PRO scores. Thresholds for clinically meaningful between-group differences were defined a priori from Cocks et al. (<i>JCO</i> 29 (1):89–96, 2011). The statistical testing of PRO endpoints was not type-1 error controlled and thus descriptive in nature.</p><p><b>Results:</b> A total of 119 patients were randomized to each treatment arm (<i>N</i> = 238). PRO completion rate was 82.1% at baseline and remained above 80% at each subsequent assessment through Week 25. CLL/SLL-related symptoms were clinically meaningfully lower in the pirtobrutinib group versus IdelaR/BR at Week 9 (LSM<sub>d</sub>, −7.3 [standard error (SE), 2.2]), Week 13 (LSM<sub>d</sub>, −6.7 [SE, 2.3]), Week 17 (LSM<sub>d</sub>, −4.6 [SE, 2.3]), and Week 21 (LSM<sub>d</sub>, −7.0 [SE, 2.3]). Patients in the pirtobrutinib group reported lower fatigue scores versus those receiving IdelaR/BR at Week 9 (LSM<sub>d</sub>, −9.0 [SE, 2.9]), Week 13 (LSM<sub>d</sub>, −6.7 [SE, 3.0]), and Week 21 (LSM<sub>d</sub>, −6.9 [SE, 3.1]). Patients in the pirtobrutinib group also reported better PF versus IdelaR/BR at Weeks 13 (LSM<sub>d</sub>, 5.6 [SE, 2.4]) and 21 (LSM<sub>d</sub>, 5.9 [SE, 2.5]).</p><p><b>Conclusions:</b> These analyses suggest a meaningful and clinically relevant improvement in CLL/SLL-related symptoms, physical functioning, and fatigue at most assessments between baseline and Week 25 in the pirtobrutinib group compared to IdelaR/BR. Most PRO assessments met clinically meaningful thresholds, and for those that did n","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_219","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Ahmed, J. L. Reguera Ortega, F. Morschhauser, G. Cartron, A. P. Rapoport, K. Izutsu, H. Ghesquieres, M. L. Palomba, H. Goto, J. Kuruvilla, J. S. Abramson, P. Borchmann, U. Jäger, M. Kamdar, M. Bar, M. Strocchia, M. Raggi, R. Nishii, A. M. García-Sancho
<p><b>Introduction:</b> In the TRANSCEND FL primary analysis, lisocabtagene maraleucel (liso-cel) showed an ORR of 97%, CR rate of 94%, and favorable safety in patients (pts) with second-line (2L) and third-line or later (3L+) R/R FL. In pts with R/R FL, increasing lines of therapy (LOT), progression of disease ≤ 24 mo from initial immunochemotherapy (POD24), and recent exposure to bendamustine (benda) before CAR T cell therapy may impact pt outcomes. We report results in these pt subgroups with R/R FL from TRANSCEND FL.</p><p><b>Methods:</b> Pts had 3L+ R/R FL or 2L R/R FL after prior treatment (tx) with an anti-CD20 antibody and alkylator. All pts with 2L R/R FL had PD ≤ 24 mo of diagnosis (dx) and tx ≤ 6 mo of FL dx, and/or modified GELF criteria. Post hoc subgroup analyses were performed by number of prior LOTs (4L+, 3L, 2L), POD24 (yes, no), and benda exposure (< 12 mo, 12–24 mo, or > 24 mo before leukapheresis or no benda). Outcomes included ORR, CR rate, duration of response (DOR), and PFS (all by IRC), OS, time to next tx (TTNT), and safety. In the benda subgroups, cellular kinetics were assessed.</p><p><b>Results:</b> Of 130 liso-cel–treated pts, 59 (45%) received liso-cel as 4L+ tx, 48 (37%) as 3L tx, and 23 (18%) as 2L tx; 73 (56%) had POD24 and 56 (43%) did not; 11 (8%) had prior benda < 12 mo, 11 (8%) within 12–24 mo, 49 (38%) > 24 mo, and 59 (45%) had no benda. Median on-study follow-up was 29.7 mo (range, 0.3–39.6). There were no major differences in demographics or baseline characteristics among subgroups.</p><p>ORR was ≥ 96% across subgroups (Table). CR rate was similar across prior LOTs and POD24 subgroups, but lower in pts with prior benda < 12 mo (75%) versus other benda subgroups (≥ 95%), though pt numbers were small in the < 12-mo group (<i>n</i> = 8). Median DOR was not reached (NR) in all but 4L+ and POD24 subgroups (30.9 mo each); median PFS was NR in all but 4L+, POD24, and no benda subgroups (31.8 mo each); and median OS was NR for all subgroups. A trend toward better 24-mo DOR, PFS, and OS was observed with liso-cel in earlier versus later LOTs. Median DOR, median PFS, and 24-mo DOR, PFS, and OS were slightly better in pts without POD24, though still clinically meaningful in pts with POD24. Rates of 24-mo DOR, PFS, and OS were high for all benda subgroups (≥ 72%) except for the 8 pts with prior benda < 12 mo where a trend for worse outcomes was observed (24-mo PFS, 50%). Median TTNT was NR for all subgroups; 24-mo rates were numerically lower for pts with 4L+ versus 3L and versus 2L FL, POD24 versus no POD24, and prior benda < 12 mo versus other benda subgroups. Cellular kinetics were similar among benda subgroups. Safety was consistent across subgroups with low rates of grade ≥ 3 cytokine release syndrome and neurological events, and no new signals observed (Table).</p><p><b>Conclusion:</b> These data support the sustained clinical benefit and manageable safety profile of liso-cel in pts with R
{"title":"LISOCABTAGENE MARALEUCEL IN R/R FL (TRANSCEND FL): IMPACT OF PRIOR LINES OF THERAPY, BENDAMUSTINE EXPOSURE, AND DISEASE PROGRESSION ≤ 24 MONTHS OF INITIAL SYSTEMIC THERAPY","authors":"S. Ahmed, J. L. Reguera Ortega, F. Morschhauser, G. Cartron, A. P. Rapoport, K. Izutsu, H. Ghesquieres, M. L. Palomba, H. Goto, J. Kuruvilla, J. S. Abramson, P. Borchmann, U. Jäger, M. Kamdar, M. Bar, M. Strocchia, M. Raggi, R. Nishii, A. M. García-Sancho","doi":"10.1002/hon.70093_142","DOIUrl":"https://doi.org/10.1002/hon.70093_142","url":null,"abstract":"<p><b>Introduction:</b> In the TRANSCEND FL primary analysis, lisocabtagene maraleucel (liso-cel) showed an ORR of 97%, CR rate of 94%, and favorable safety in patients (pts) with second-line (2L) and third-line or later (3L+) R/R FL. In pts with R/R FL, increasing lines of therapy (LOT), progression of disease ≤ 24 mo from initial immunochemotherapy (POD24), and recent exposure to bendamustine (benda) before CAR T cell therapy may impact pt outcomes. We report results in these pt subgroups with R/R FL from TRANSCEND FL.</p><p><b>Methods:</b> Pts had 3L+ R/R FL or 2L R/R FL after prior treatment (tx) with an anti-CD20 antibody and alkylator. All pts with 2L R/R FL had PD ≤ 24 mo of diagnosis (dx) and tx ≤ 6 mo of FL dx, and/or modified GELF criteria. Post hoc subgroup analyses were performed by number of prior LOTs (4L+, 3L, 2L), POD24 (yes, no), and benda exposure (< 12 mo, 12–24 mo, or > 24 mo before leukapheresis or no benda). Outcomes included ORR, CR rate, duration of response (DOR), and PFS (all by IRC), OS, time to next tx (TTNT), and safety. In the benda subgroups, cellular kinetics were assessed.</p><p><b>Results:</b> Of 130 liso-cel–treated pts, 59 (45%) received liso-cel as 4L+ tx, 48 (37%) as 3L tx, and 23 (18%) as 2L tx; 73 (56%) had POD24 and 56 (43%) did not; 11 (8%) had prior benda < 12 mo, 11 (8%) within 12–24 mo, 49 (38%) > 24 mo, and 59 (45%) had no benda. Median on-study follow-up was 29.7 mo (range, 0.3–39.6). There were no major differences in demographics or baseline characteristics among subgroups.</p><p>ORR was ≥ 96% across subgroups (Table). CR rate was similar across prior LOTs and POD24 subgroups, but lower in pts with prior benda < 12 mo (75%) versus other benda subgroups (≥ 95%), though pt numbers were small in the < 12-mo group (<i>n</i> = 8). Median DOR was not reached (NR) in all but 4L+ and POD24 subgroups (30.9 mo each); median PFS was NR in all but 4L+, POD24, and no benda subgroups (31.8 mo each); and median OS was NR for all subgroups. A trend toward better 24-mo DOR, PFS, and OS was observed with liso-cel in earlier versus later LOTs. Median DOR, median PFS, and 24-mo DOR, PFS, and OS were slightly better in pts without POD24, though still clinically meaningful in pts with POD24. Rates of 24-mo DOR, PFS, and OS were high for all benda subgroups (≥ 72%) except for the 8 pts with prior benda < 12 mo where a trend for worse outcomes was observed (24-mo PFS, 50%). Median TTNT was NR for all subgroups; 24-mo rates were numerically lower for pts with 4L+ versus 3L and versus 2L FL, POD24 versus no POD24, and prior benda < 12 mo versus other benda subgroups. Cellular kinetics were similar among benda subgroups. Safety was consistent across subgroups with low rates of grade ≥ 3 cytokine release syndrome and neurological events, and no new signals observed (Table).</p><p><b>Conclusion:</b> These data support the sustained clinical benefit and manageable safety profile of liso-cel in pts with R","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_142","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. M. Linton, I. Karpha, Y. Lim, M. Bishton, L. Jeffers, T. Erinfolami, N. Akter, H. Liu, B. Johnston, N. Kalakonda, C. Tudur Smith, M. Clancy, A. Pettitt
Introduction: UNCOVER is a blood cancer health data research programme that utilises the National Cancer Registration Dataset (NCRD). NCRD includes information on all patients diagnosed with all types of cancer in all NHS institutions in England (Int J Epidemiol 2020; 49(1):16–16h).
Methods: NCRD data was obtained for all patients in England diagnosed with any type of blood cancer between Jan 2014 and Dec 2021. Patients with newly diagnosed follicular lymphoma (FL) were identified using ICD-O-3 codes 96953, 96913, 96983, and 96903. Crude and adjusted incidence rate ratios (IRR) were estimated and compared between groups using multivariable Poisson regression, and calendar time trends were assessed. Overall survival (OS), cause-specific and relative survival was assessed using K-M methods and multivariable Cox regression, Fine-Gray and Pohar-Perme models, respectively. All models were adjusted for age, gender, index of multiple deprivation (IMD) quintile and government region, while Cox and Fine-Gray models were also adjusted for ethnicity and Charlson co-morbidity index (CCI).
Results: 17561 patients with FL aged 18–99 were identified (demographics in Table 1). Gender (p < 0.001), age (p < 0.001), ethnicity (p < 0.001), region (p < 0.001) and year of diagnosis (p < 0.001) were independently associated with incidence. The adjusted IRR increased with age and was lower in females (0.90), in mixed-race (0.20), Asian (0.43) and black (0.28) people compared to white people, and in all 8 provincial regions compared to London (IRR for North West 0.81). The adjusted IRR for successive calendar years was generally stable but dipped in the first year of the COVID-19 pandemic [2020 vs. 2014; 0.94 (95% CI: 0.89–1.01)]. Survival data were available until July 2023 [median follow-up 4.4 years (IQR: 2.4–6.6)]. 4709 (26.8%) patients died, with 5-year OS 74% (95% CI: 74%–75%) and relative survival 85% (84%–86%). Gender (p < 0.001), age (p < 0.001), ethnicity (p = 0.044), CCI (p < 0.001), IMD (p < 0.001) and year of diagnosis (p = 0.008) were independently associated with OS. The adjusted hazard ratio (HR) increased with age [15.4 (95% CI: 11.6–20.6) for 75–99 vs. 18–44], deprivation [1.47 (1.33–1.61) for IMD1 vs. IMD5] and comorbidity [2.35 (2.09–2.64) for CCI ≥ 4 vs. 0] but was lower in females [0.78 (0.73–0.82)], in black versus white people [0.60 (0.38–0.93)], and in patients diagnosed in 2015 versus 2014 [0.86 (0.78–0.96)].
Conclusion: Our findings shed new light on FL epidemiology and outcomes in England during the period 2014–2021. Even when other variables such as age and comorbidity were taken into account, reported incidence was lower and survival shorter in people living in more deprived areas, identifying a group with significant unmet needs. A significant proportion of patients died of unrelated
{"title":"FOLLICULAR LYMPHOMA EPIDEMIOLOGY AND OUTCOMES IN ENGLAND 2014–2021: PRELIMINARY ANALYSIS FROM THE UNCOVER STUDY GROUP","authors":"K. M. Linton, I. Karpha, Y. Lim, M. Bishton, L. Jeffers, T. Erinfolami, N. Akter, H. Liu, B. Johnston, N. Kalakonda, C. Tudur Smith, M. Clancy, A. Pettitt","doi":"10.1002/hon.70093_96","DOIUrl":"https://doi.org/10.1002/hon.70093_96","url":null,"abstract":"<p><b>Introduction</b>: UNCOVER is a blood cancer health data research programme that utilises the National Cancer Registration Dataset (NCRD). NCRD includes information on all patients diagnosed with all types of cancer in all NHS institutions in England (<i>Int J Epidemiol</i> 2020; 49(1):16–16h).</p><p><b>Methods</b>: NCRD data was obtained for all patients in England diagnosed with any type of blood cancer between Jan 2014 and Dec 2021. Patients with newly diagnosed follicular lymphoma (FL) were identified using ICD-O-3 codes 96953, 96913, 96983, and 96903. Crude and adjusted incidence rate ratios (IRR) were estimated and compared between groups using multivariable Poisson regression, and calendar time trends were assessed. Overall survival (OS), cause-specific and relative survival was assessed using K-M methods and multivariable Cox regression, Fine-Gray and Pohar-Perme models, respectively. All models were adjusted for age, gender, index of multiple deprivation (IMD) quintile and government region, while Cox and Fine-Gray models were also adjusted for ethnicity and Charlson co-morbidity index (CCI).</p><p><b>Results</b>: 17561 patients with FL aged 18–99 were identified (demographics in Table 1). Gender (<i>p</i> < 0.001), age (<i>p</i> < 0.001), ethnicity (<i>p</i> < 0.001), region (<i>p</i> < 0.001) and year of diagnosis (<i>p</i> < 0.001) were independently associated with incidence. The adjusted IRR increased with age and was lower in females (0.90), in mixed-race (0.20), Asian (0.43) and black (0.28) people compared to white people, and in all 8 provincial regions compared to London (IRR for North West 0.81). The adjusted IRR for successive calendar years was generally stable but dipped in the first year of the COVID-19 pandemic [2020 vs. 2014; 0.94 (95% CI: 0.89–1.01)]. Survival data were available until July 2023 [median follow-up 4.4 years (IQR: 2.4–6.6)]. 4709 (26.8%) patients died, with 5-year OS 74% (95% CI: 74%–75%) and relative survival 85% (84%–86%). Gender (<i>p</i> < 0.001), age (<i>p</i> < 0.001), ethnicity (<i>p</i> = 0.044), CCI (<i>p</i> < 0.001), IMD (<i>p</i> < 0.001) and year of diagnosis (<i>p</i> = 0.008) were independently associated with OS. The adjusted hazard ratio (HR) increased with age [15.4 (95% CI: 11.6–20.6) for 75–99 vs. 18–44], deprivation [1.47 (1.33–1.61) for IMD1 vs. IMD5] and comorbidity [2.35 (2.09–2.64) for CCI ≥ 4 vs. 0] but was lower in females [0.78 (0.73–0.82)], in black versus white people [0.60 (0.38–0.93)], and in patients diagnosed in 2015 versus 2014 [0.86 (0.78–0.96)].</p><p><b>Conclusion</b>: Our findings shed new light on FL epidemiology and outcomes in England during the period 2014–2021. Even when other variables such as age and comorbidity were taken into account, reported incidence was lower and survival shorter in people living in more deprived areas, identifying a group with significant unmet needs. A significant proportion of patients died of unrelated","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_96","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R. Tao, C. Liu, W. Zhang, J. Wan, Y. Ma, Y. Zhu, L. Ma, S. Tian, H. Ding
<p><b>Introduction:</b> Stage IV Natural killer/T-cell lymphoma (NKTCL) has a poor prognosis. Asparaginase is the backbone drug for the treatment of NKTCL. Anti-PD-1 antibody is effective for relapsed/refractory NKTCL. Our previous study found that angiogenesis inhibitor anlotinib was active in relapsed/refractory NKTCL. This study is aimed to investigate the efficacy and safety of Sintilimab, a PD-1 antibody approved in China, in combination with Pegaspargase and anlotinib (LEAP regimen) in the treatment of stage IV NKTCL patients unfit for high-dose induction chemotherapy.</p><p><b>Methods:</b> Eligible patients met the following criteria: (1) Histologically confirmed NKTCL with stage IV classification per Lugano 2014 criteria; (2) Age > 65 years or ≤ 65 years with protocol-defined contraindications to high-dose methotrexate/dexamethasone. The LEAP regimen comprised 3-week cycles (maximum 8 cycles): Sintilimab 200 mg IV day 1; Pegaspargase 2500 IU/m<sup>2</sup> IM day 1; Anlotinib 8 mg PO days 1–14. Complete responders could receive consolidative autologous hematopoietic stem cell transplantation (auto-HSCT) at investigator discretion. The primary endpoint was complete response (CR) rate at 24 weeks by Lugano 2014 criteria. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety analysis using CTCAE v4.0.</p><p><b>Results:</b> Thirty-seven patients were enrolled (median age 64 years; range 32–78; M:F = 22:15) from July 2019 to April 2021. The median treatment duration was 8 cycles (range 2–8), with 72.9% (27/37) achieving CR and an objective response rate of 83.8% (31/37). Disease progression occurred in 16.2% (6/37) during treatment. Following induction therapy, 63.0% (17/27) of CR patients underwent consolidative auto-HSCT versus 37.0% (10/27) who entered observation. With a median follow-up of 48 months (95% CI: 45.2–50.8), the auto-HSCT cohort demonstrated significantly lower relapse rates (17.6% vs. 60.0%, <i>p</i> < 0.05). Survival outcomes revealed 1-/4-year PFS rates of 78.4% (95% CI: 61.4%–88.6%)/56.6% (39.2%–70.7%) and 1-/4-year OS rates of 83.8% (67.4%–92.4%)/75.2% (57.7%–86.3%). All patients experienced treatment-related adverse events (AEs), predominantly grade 1–2 asparaginase-associated toxicities). Grade ≥ 3 AEs included neutropenia (10.8%) and hyperbilirubinemia (10.8%). No AE-related treatment discontinuations occurred.</p><p><b>Conclusions:</b> The LEAP regimen demonstrates robust clinical efficacy (CR rate 72.9%) and favorable tolerability in high-risk stage IV NKTCL patients ineligible for intensive induction chemotherapy. However, the high post-remission relapse rate (60%) in non-consolidated patients underscores the necessity for effective maintenance strategies. Our findings suggest consolidative auto-HSCT significantly improves disease free survival, potentially bridging the gap between immunotherapy and durable remission in this challenging patient population.</p><p><b>Keyw
{"title":"A MULTI-CENTER, PROSPECTIVE STUDY OF THE EFFICACY AND SAFETY OF PD-1 ANTIBODY SINTILIMAB IN COMBINATION WITH PEGASPARGASE AND ANLOTINIB IN STAGE IV NKTCL PATIENTS","authors":"R. Tao, C. Liu, W. Zhang, J. Wan, Y. Ma, Y. Zhu, L. Ma, S. Tian, H. Ding","doi":"10.1002/hon.70094_400","DOIUrl":"https://doi.org/10.1002/hon.70094_400","url":null,"abstract":"<p><b>Introduction:</b> Stage IV Natural killer/T-cell lymphoma (NKTCL) has a poor prognosis. Asparaginase is the backbone drug for the treatment of NKTCL. Anti-PD-1 antibody is effective for relapsed/refractory NKTCL. Our previous study found that angiogenesis inhibitor anlotinib was active in relapsed/refractory NKTCL. This study is aimed to investigate the efficacy and safety of Sintilimab, a PD-1 antibody approved in China, in combination with Pegaspargase and anlotinib (LEAP regimen) in the treatment of stage IV NKTCL patients unfit for high-dose induction chemotherapy.</p><p><b>Methods:</b> Eligible patients met the following criteria: (1) Histologically confirmed NKTCL with stage IV classification per Lugano 2014 criteria; (2) Age > 65 years or ≤ 65 years with protocol-defined contraindications to high-dose methotrexate/dexamethasone. The LEAP regimen comprised 3-week cycles (maximum 8 cycles): Sintilimab 200 mg IV day 1; Pegaspargase 2500 IU/m<sup>2</sup> IM day 1; Anlotinib 8 mg PO days 1–14. Complete responders could receive consolidative autologous hematopoietic stem cell transplantation (auto-HSCT) at investigator discretion. The primary endpoint was complete response (CR) rate at 24 weeks by Lugano 2014 criteria. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety analysis using CTCAE v4.0.</p><p><b>Results:</b> Thirty-seven patients were enrolled (median age 64 years; range 32–78; M:F = 22:15) from July 2019 to April 2021. The median treatment duration was 8 cycles (range 2–8), with 72.9% (27/37) achieving CR and an objective response rate of 83.8% (31/37). Disease progression occurred in 16.2% (6/37) during treatment. Following induction therapy, 63.0% (17/27) of CR patients underwent consolidative auto-HSCT versus 37.0% (10/27) who entered observation. With a median follow-up of 48 months (95% CI: 45.2–50.8), the auto-HSCT cohort demonstrated significantly lower relapse rates (17.6% vs. 60.0%, <i>p</i> < 0.05). Survival outcomes revealed 1-/4-year PFS rates of 78.4% (95% CI: 61.4%–88.6%)/56.6% (39.2%–70.7%) and 1-/4-year OS rates of 83.8% (67.4%–92.4%)/75.2% (57.7%–86.3%). All patients experienced treatment-related adverse events (AEs), predominantly grade 1–2 asparaginase-associated toxicities). Grade ≥ 3 AEs included neutropenia (10.8%) and hyperbilirubinemia (10.8%). No AE-related treatment discontinuations occurred.</p><p><b>Conclusions:</b> The LEAP regimen demonstrates robust clinical efficacy (CR rate 72.9%) and favorable tolerability in high-risk stage IV NKTCL patients ineligible for intensive induction chemotherapy. However, the high post-remission relapse rate (60%) in non-consolidated patients underscores the necessity for effective maintenance strategies. Our findings suggest consolidative auto-HSCT significantly improves disease free survival, potentially bridging the gap between immunotherapy and durable remission in this challenging patient population.</p><p><b>Keyw","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_400","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Relapsed and refractory (r/r) mature B-NHL in chidlren and adolescents represents an area of unmet cinical need due to the poor prognosis of these patients. Burkitt lymphoma and Diffuse Large B-cell lymphoma are the majority histologies.
Mulitple new immuno-oncology therapies are available or being investigated in adult r/r mature B-NHL. The rarity of childhod and adolescent disease makes evaluation of all of these impossible and a more strategic approach is required.
This lecture will explore the challenges of rational new drug development in this rare disease and highlight the current landscape with an emphasis on an international, transatlantic, academic-industry collaborative, fit-for-filing trial -Glo-BNHL (NCT05991388)
Researchfunding declaration: CRUK, FKC, Multiple industry partners.
Keywords: non-Hodgkin (Pediatric, Adolescent, and Young Adult); immunotherapy; ongoing trials
Potential sources of conflict of interest:
A. Burke
Other remuneration: Institutional funding from Regeneron, ADCT Therapeutics and BMS for clinical trial
{"title":"RELAPSED/REFRACTORY MATURE B-NHL IN CHILDREN AND ADOLESCENTS","authors":"A. Burke","doi":"10.1002/hon.70093_31","DOIUrl":"https://doi.org/10.1002/hon.70093_31","url":null,"abstract":"<p>Relapsed and refractory (r/r) mature B-NHL in chidlren and adolescents represents an area of unmet cinical need due to the poor prognosis of these patients. Burkitt lymphoma and Diffuse Large B-cell lymphoma are the majority histologies.</p><p>Mulitple new immuno-oncology therapies are available or being investigated in adult r/r mature B-NHL. The rarity of childhod and adolescent disease makes evaluation of all of these impossible and a more strategic approach is required.</p><p>This lecture will explore the challenges of rational new drug development in this rare disease and highlight the current landscape with an emphasis on an international, transatlantic, academic-industry collaborative, fit-for-filing trial -Glo-BNHL (NCT05991388)</p><p><b>Research</b> <b>funding declaration:</b> CRUK, FKC, Multiple industry partners.</p><p><b>Keywords:</b> non-Hodgkin (Pediatric, Adolescent, and Young Adult); immunotherapy; ongoing trials</p><p><b>Potential sources of conflict of interest:</b></p><p><b>A. Burke</b></p><p><b>Other remuneration:</b> Institutional funding from Regeneron, ADCT Therapeutics and BMS for clinical trial</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_31","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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