Hematological Oncology最新文献

{"title":"Synthetic Lethal Combinations of DNA Repair Inhibitors and Genotoxic Agents to Target High-Risk Diffuse Large B Cell Lymphoma","authors":"Sara Ovejero,&nbsp;Julie Devin,&nbsp;Laura Alibert,&nbsp;Camille Soun,&nbsp;Yea-Lih Lin,&nbsp;Laure Dutrieux,&nbsp;Matthieu Abouladze,&nbsp;Elvira Garcia de Paco,&nbsp;Ouissem Karmous Gadacha,&nbsp;Angelos Constantinou,&nbsp;Guillaume Cartron,&nbsp;Charles Herbaux,&nbsp;Olivier Elemento,&nbsp;Philippe Pasero,&nbsp;Sandrine Roulland,&nbsp;Jérôme Moreaux,&nbsp;Caroline Bret","doi":"10.1002/hon.70131","DOIUrl":"https://doi.org/10.1002/hon.70131","url":null,"abstract":"<p>Diffuse large B-cell lymphoma (DLBCL) is the most common hematological malignancy. More than half of DLBCL patients achieve long-term remission after treatment, but a third relapse after conventional Rituximab (R)-based chemotherapy regimens, such as CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone). Cancer cells are exposed to chronic replication stress, which impedes the duplication of their genome. Functional DNA repair pathways are therefore important for the survival of cancer cells. This dependence can be exploited therapeutically to hamper repair of the intrinsic DNA damage occurring during replication or to exacerbate DNA damage induced by chemotherapy. Using CRISPR-Cas9 screening, we identified <i>CHEK1, WEE1, ATR</i> and <i>RAD51</i> DNA repair factors as essential genes in DLBCL cells. According to these results, we investigated the effect of small molecules targeting DNA replication stress and DNA repair mechanisms, alone or in combination with the R-CHOP genotoxic agents, cyclophosphamide and doxorubicin. Applying a standard threshold of 2 SDs below the IC50 of the genotoxic agent alone, a total of 3 synthetic lethal combinations have been identified including cyclophosphamide with CHK1/2 inhibitor, cyclophosphamide and ATR inhibitor and doxorubicin with DNAPK inhibitor. Co-treatment with these molecules led to cell death, DNA damage induction and cell cycle arrest in DLBCL cells more efficiently than genotoxic agents alone. These data have been validated using primary DLBCL cells from patients. Our results open new perspectives for therapeutic approaches exploiting the synthetic lethality of genotoxic agents with DNA repair inhibitors to improve the therapeutic outcome of patients with DLBCL.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70131","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144891787","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}

{"title":"Management of Adverse Reactions to Loncastuximab in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma","authors":"Narendranath Epperla,&nbsp;Adam J. Olszewski,&nbsp;Emily C. Ayers,&nbsp;Sairah Ahmed","doi":"10.1002/hon.70128","DOIUrl":"https://doi.org/10.1002/hon.70128","url":null,"abstract":"<p>Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell non-Hodgkin lymphoma in the world. Treatment options for relapsed DLBCL in the third line and beyond include chimeric antigen receptor T-cell therapy, T-cell–engaging bispecific antibodies, and loncastuximab tesirine (loncastuximab tesirine-lpyl [Lonca]), each with unique toxicity profiles. There is still an unmet need for guidance on managing Lonca-associated adverse events (AEs), particularly for oncologists who have limited experience with this antibody–drug conjugate. Here, an online survey among lymphoma specialists in the US between June and August 2024 assessed practice patterns and experiences, including Lonca treatment patterns, AE management, patient concerns, and physician perceptions. Based on these responses, an algorithm was developed to help manage Lonca-associated AEs. The most commonly reported AEs were edema and rash/photosensitivity, typically occurring within the first 4 doses, whereas fatigue was the most common patient concern. Lonca-associated AEs were managed by delaying or discontinuing Lonca or by prescribing diuretics, steroids, or antihistamines, depending on the AE observed. The survey results align with findings from prior clinical trials and support the manageability of Lonca-associated AEs in a wide variety of settings. The included algorithm provides guidance for managing AEs, such as edema, myelosuppression, and cutaneous reactions.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881319","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}

{"title":"Evaluation of Delayed Initiation of Lenalidomide Maintenance Therapy After Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma","authors":"Koji Kawamura,&nbsp;Nobuhiro Tsukada,&nbsp;Shun-ichi Kimura,&nbsp;Shinichi Kako,&nbsp;Daisuke Minakata,&nbsp;Terukazu Enami,&nbsp;Yasuharu Hamano,&nbsp;Go Yamamoto,&nbsp;Shuichi Ota,&nbsp;Naoshi Obara,&nbsp;Kiyoshi Ando,&nbsp;Kenshi Suzuki,&nbsp;Yoshinobu Kanda","doi":"10.1002/hon.70129","DOIUrl":"https://doi.org/10.1002/hon.70129","url":null,"abstract":"<div>\u0000 \u0000 <p>Although allogeneic hematopoietic stem cell transplantation (allo-HCT) is considered a potentially curative therapy for multiple myeloma, disease progression after allo-HCT remains a major limitation. Post-transplant maintenance therapy may help reduce the risk of relapse. Lenalidomide, an immunomodulatory agent, has demonstrated efficacy in multiple myeloma, but its use after allo-HCT is limited due to concerns regarding graft-versus-host disease (GVHD). To evaluate the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of lenalidomide when used as maintenance therapy after allo-HCT for multiple myeloma. This was a prospective, multicenter, phase I/II clinical trial conducted from 2014 to 2019. Lenalidomide maintenance therapy was initiated 100–365 days post-allo-HCT. Eligible patients received lenalidomide on days 1–21 of a 28-day cycle for at least four cycles, beginning at 5 mg/day. A standard 3 + 3 dose-escalation design (Fibonacci method) was used to determine DLT and MTD. The study included 10 patients; one was excluded due to early disease progression, leaving nine patients evaluable for toxicity. The phase II portion was not conducted due to expiration of the trial period. The median interval from allo-HCT to initiation of lenalidomide was 244 days (range, 169–330 days). At the 10 mg/day dose level, one patient experienced moderate chronic GVHD meeting the predefined criteria for DLT. No other DLTs occurred, establishing the MTD at 10 mg/day. No acute GVHD was observed. Two additional patients developed mild chronic GVHD, which resolved spontaneously without treatment. The 2-year progression-free survival (PFS) and overall survival (OS) rates from the start of maintenance therapy were 53% and 78%, respectively. Late initiation of lenalidomide maintenance therapy after allo-HCT for multiple myeloma was feasible at a dose of 10 mg/day and was associated with a low incidence of GVHD-related complications. However, further studies are required to confirm treatment efficacy.</p>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861818","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}

{"title":"Oncogenic IRF3 Signaling Promotes Diffused Large B-Cell Lymphoma Proliferation by Cyclin D3/CDK4-Dependent Cell Cycle Control","authors":"Bide Zhao,&nbsp;Linjing Shi,&nbsp;Xiao Yang","doi":"10.1002/hon.70127","DOIUrl":"https://doi.org/10.1002/hon.70127","url":null,"abstract":"<div>\u0000 \u0000 <p>Diffuse large B-cell lymphoma (DLBCL), the most aggressive non-Hodgkin lymphoma subtype, is cured in 60%–70% of patients with frontline chemoimmunotherapy. For refractory/relapsed cases, deciphering DLBCL's molecular drivers could unveil new therapies to overcome resistance and enhance survival. Interferon regulatory factor 3 (IRF3) is a transcription factor that drives type I interferon responses, crucial for antiviral defense against DNA and RNA viruses. Emerging evidences implicate IRF3 in the malignant progression of gastric cancer, hepatocellular carcinoma, and multiple myeloma. However, its biological role and prognostic significance in DLBCL need further investigation. Here, we examined the expression level of IRF3 in DLBCL patient samples. Functional impact on proliferation was assessed by MTS and EdU assays, while mechanistic insights were obtained through cell cycle analysis and apoptosis evaluation. As a result, IRF3 expression was significantly elevated in DLBCL patients compared to controls and correlated with poorer clinical outcomes. Notably, increased expression of IRF3 induced by poly I:C or poly dA:dT enhanced DLBCL cells proliferation, whereas IRF3 knockdown suppressed this effect. Furthermore, IRF3 promoted G1/S phase transition by upregulating cyclin D3 and CDK4 expression. Collectively, IRF3 regulates DLBCL cell proliferation by controlling G1/S transition via cyclin D3 and CDK4. Thus, our study identifies IRF3 as a novel regulator of DLBCL proliferation, highlighting its potential as a therapeutic target in DLBCL.</p>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144853756","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}

{"title":"The Role of Different Risk Groups and Treatment Assignment Probabilities in Subgroup Analysis of Randomized Trials","authors":"Vadim Lesan,&nbsp;Vlada Odaie,&nbsp;Cristian Munteanu","doi":"10.1002/hon.70132","DOIUrl":"https://doi.org/10.1002/hon.70132","url":null,"abstract":"<div>\u0000 \u0000 <p>Retrospective subgroup analyses can introduce significant bias in the estimation of hazard ratios (HRs), particularly when patient distributions across treatment arms are imbalanced. Such disparities can distort the validity of HR outcomes, especially in the presence of unequal risk group compositions and varying treatment assignment probabilities. These factors may artificially shift HR estimates across different risk populations, leading to misleading correlations between subgroup classifications and treatment effects. To quantify this phenomenon, we conducted Monte Carlo simulations across 1000 trials, demonstrating how hazard ratios vary systematically with changes in the underlying risk group population. These findings underscore the need for caution in interpreting HRs from subgroup analyses and highlight the importance of robust trial design to mitigate bias.</p>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144853755","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}

{"title":"Lomustine, Etoposide and Cyclophosphamide as Conditioning for Auto-HCT in Lymphomas","authors":"Rafaella Cabral Samico,&nbsp;Júlia Diniz Ferreira,&nbsp;Christianne Tolêdo de Souza Leal,&nbsp;Kelli Borges dos Santos,&nbsp;Ana Carolina Xavier,&nbsp;Abrahão Elias Hallack Neto","doi":"10.1002/hon.70122","DOIUrl":"https://doi.org/10.1002/hon.70122","url":null,"abstract":"","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144853754","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}

{"title":"Real World Incidence and Etiology of Infectious Complications in Adults With Ph-Negative Acute Lymphoblastic Leukemia Treated With the Pediatric-Inspired GIMEMA LAL1913 Program. A Campus All Study","authors":"Patrizia Zappasodi,&nbsp;Ludovica Calabretta,&nbsp;Virginia Valeria Ferretti,&nbsp;Davide Lazzarotto,&nbsp;Nicola Fracchiolla,&nbsp;Marco Cerrano,&nbsp;Cristina Papayannidis,&nbsp;Sabina Chiaretti,&nbsp;Maria Ilaria Del Principe,&nbsp;Valentina Mancini,&nbsp;Monia Lunghi,&nbsp;Fabio Forghieri,&nbsp;Sara Mastaglio,&nbsp;Michelina Dargenio,&nbsp;Crescenza Pasciolla,&nbsp;Carla Mazzone,&nbsp;Beatrice Sani,&nbsp;Fabio Guolo,&nbsp;Marzia Defina,&nbsp;Maria Ciccone,&nbsp;Elisa Roncoroni,&nbsp;Marianna Rossi,&nbsp;Claudia Patricia Tobar Cabrera,&nbsp;Gianluca Martini,&nbsp;Giacomo Riccaboni,&nbsp;Luca Arcaini,&nbsp;Robin Foà,&nbsp;Anna Candoni","doi":"10.1002/hon.70121","DOIUrl":"https://doi.org/10.1002/hon.70121","url":null,"abstract":"<p>Infections often complicate pediatric-inspired treatments for adult Philadelphia-negative acute lymphoblastic leukemia (Ph- ALL). Literature data on these complications are difficult to interpret due to the heterogeneity of types of infections analyzed or patients and treatment characteristics. A deeper insight on the infections occurring in the real life in uniformly treated ALL patients is lacking. This study investigated infectious complications in 240 newly diagnosed adult Ph- ALL patients treated in the real life according to the GIMEMA LAL1913 protocol by 18 Italian centers participating in the Campus ALL network. Incidence, etiology of microbiologically documented infections and invasive fungal infections (IFI) and mortality for infection were determined. Potential risk factors and the prophylactic strategies used during the first chemotherapy course (C1) were analyzed. Of 240 patients, 145 (60%) experienced at least one infectious episode, with bacterial infections being the most common (74.3%), followed by viral (13.9%), fungal (10.1%), and Pneumocystis jirovecii (1.7%) infections. The blood stream was the most involved site, pneumonia occurred in 14.6% of cases, half of which being fungal. Infections were prevalent during C1, affecting 40.5% of patients; IFI occurred in 12.5% of patients, most of them in C1. Risk factors for infections included older age (≥ 55 years and particularly &gt; 65 years) and comorbidities only for IFI. The mortality rate for infection was 3.3%. Antibacterial, antiviral, antifungal, and anti-PJ prophylaxis were variably administered and did not associate with a significant reduced infection rate. In conclusion, the rate of infectious complications in the real life of adult Ph- ALL patients treated with a pediatric-inspired intensive regimen is high, mainly during induction and mostly bacterial, particularly in the bloodstream, with a high IFI rate. Older age, mainly over 65 years, is a risk factor for all types of infection. The antimicrobial prophylaxis was not associated to a reduced risk of infection.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70121","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811004","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}

{"title":"Elranatamab for Relapsed/Refractory Multiple Myeloma With Severe Renal Impairment Requiring Hemodialysis","authors":"Michèle Hoffmann,&nbsp;Barbara Jeker,&nbsp;Uyen Huynh-Do,&nbsp;Yara Banz,&nbsp;Jeanne Godau,&nbsp;Elisabeth Weber,&nbsp;Ulrike Bacher,&nbsp;Thomas Pabst","doi":"10.1002/hon.70120","DOIUrl":"https://doi.org/10.1002/hon.70120","url":null,"abstract":"<p>Relapsed/refractory multiple myeloma (RRMM) patients with dialysis-dependent renal impairment face limited therapeutic options due to exclusion from clinical trials, a lack of evidence-based guidelines, and inferior outcomes. Bispecific antibodies targeting B-cell maturation antigen (BCMA) have shown promise in RRMM treatment but remain understudied in this vulnerable population. To illustrate this issue, we introduce the case of a 68-year-old female with triple-class RRMM and end-stage renal disease requiring hemodialysis, treated with elranatamab as a second line treatment following progression after therapy with daratumumab, bortezomib, lenalidomide, and dexamethasone. Despite experiencing grade I cytokine release syndrome during the initial administrations, symptoms were managed effectively with tocilizumab and dexamethasone, allowing treatment continuation. The patient achieved a very good partial remission within 7 weeks. Although hemodialysis dependence persisted, the therapy was well-tolerated with manageable adverse events. According to the literature, BCMA-directed immunotherapies, including teclistamab, belantamab mafodotin, and idecabtagene vicleucel, have shown efficacy in dialysis-dependent RRMM patients, though data remain limited. Pharmacokinetic analyses indicate that mild or moderate renal impairment does not have a significant impact on the pharmacokinetics of elranatamab. Although no retrospective studies or case series have investigated the use of elranatamab in dialysis-dependent patients, a single case report suggests that its administration is both feasible and well-tolerated in this population despite the absence of comprehensive pharmacokinetic data. This review highlights feasibility, safety, and encouraging efficacy of elranatamab in managing RRMM in a dialysis-dependent patient, representing the second case report in the literature. By providing real-world evidence for the use of bispecific antibodies in end stage renal disease patients, this review emphasizes the potential for expanding therapeutic options to this vulnerable population while highlighting the need for vigilant monitoring of infection prevention and management. Prospective studies are warranted to validate these findings and optimize therapeutic strategies for patients with RRMM and severe renal impairment.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70120","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144663792","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}

{"title":"Deubiquitinase TRIM44 Promotes Autophagy-Mediated Chemoresistance in Diffuse Large B Cell Lymphoma","authors":"Yan Wang,&nbsp;Banban Li,&nbsp;Yanan Zhao,&nbsp;Xunxun Zhu,&nbsp;Bo Wang,&nbsp;Lizhe Yang,&nbsp;Rui Feng,&nbsp;Qingliang Teng","doi":"10.1002/hon.70119","DOIUrl":"https://doi.org/10.1002/hon.70119","url":null,"abstract":"<p>Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Tripartite motif containing 44 (TRIM44) belonging to the TRIM family, is involved in tumor development and is highly expressed in a variety of tumors. However, the role of TRIM44 in DLBCL remains undefined. Gain and loss-of-function studies were performed on lymphoblast cell lines DB and SU-DHL-4 to investigate its function. TRIM44 overexpression significantly promoted cell proliferation and viability, whereas its silencing inhibited proliferation and induced apoptosis. TRIM44 overexpression upregulated the LC3II/LC3-I ratio and Beclin1 expression, as well as increased autophagosomes formation, suggesting autophagy activation. Notably, TRIM44 conferred chemoresistance to doxorubicin in DB cells by increasing autophagic activity. In vivo study on mice revealed that TRIM44 overexpression increased Ki67 and PCNA expression, suggesting an increased tumor growth. Our previous work revealed that miR-665 is a tumor suppressor in DLBCL. The results of miRNA pull-down and luciferase reporter assay indicated that TRIM44 was a direct target of miR-665. In conclusion, TRIM44 promoted DLBCL progression by increasing autophagy-mediated chemoresistance, revealing the involvement of miR-665/TRIM44 axis.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70119","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647218","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}

{"title":"Impact of Body Composition on Treatment Toxicity and Outcomes in Patients With Primary Mediastinal Large B-Cell Lymphoma","authors":"Juliette Penichoux,&nbsp;Pierre Decazes,&nbsp;Cédric Rossi,&nbsp;Pierre Sesques,&nbsp;Corinne Haioun,&nbsp;Eric Durot,&nbsp;Nicolas Gower,&nbsp;Alexandre Willaume,&nbsp;Lucie Oberic,&nbsp;Jérome Paillassa,&nbsp;Chloé Antier,&nbsp;Loic Renaud,&nbsp;Olivier Tournilhac,&nbsp;Catherine Thieblemont,&nbsp;Caroline Besson,&nbsp;Laure Lebras,&nbsp;Sylvain Choquet,&nbsp;Katell Le Du,&nbsp;Christophe Bonnet,&nbsp;Sarah Bailly,&nbsp;Ghandi Damaj,&nbsp;Kamel Laribi,&nbsp;Roch Houot,&nbsp;Adrien Chauchet,&nbsp;Stéphanie Becker,&nbsp;David Tonnelet,&nbsp;Hervé Tilly,&nbsp;Fabrice Jardin,&nbsp;Emilie Lévêque,&nbsp;Vincent Camus","doi":"10.1002/hon.70117","DOIUrl":"https://doi.org/10.1002/hon.70117","url":null,"abstract":"<p>Primary mediastinal large B-cell lymphoma (PMBL) is a rare entity that predominantly affects young female patients and typically presents as a large and compressive anterior mediastinal mass. Accumulating evidence suggests relationships among PMBL patient body composition (BC), cancer outcomes, and treatment-related toxicities. The aim of this study was to evaluate the impact of BC on PMBL patients using PET-CT images acquired pretreatment. Two hundred nineteen patients were included in an ancillary analysis of a multicenter retrospective LYSA cohort of treatment-naïve adult PMBL patients who received first-line treatment with ACVBP, CHOP14 or CHOP21 plus anti-CD20. Anthropometric parameters were assessed from the baseline PET-CT image using two methods: (i) manual segmentation at the L3 level and (ii) automatic software-based multislice measurements with Anthropometer3DNet. The median age was 35.4 years (range 18–88 years), and the median body mass index was 23.8 kg/m² (15.6; 40.8). Overall, 137 patients were treated with R-ACVBP, 44 received R-CHOP14, and 38 were treated with R-CHOP21. Patients with low lean body mass had a higher incidence of febrile neutropenia, both in the overall cohort (25% vs. 12.6%, <i>p</i> = 0.02) and in the R-ACVBP subgroup (35.7% vs. 19.4%, <i>p</i> = 0.03). Univariate analysis showed that in patients treated with R-ACVBP, subcutaneous low adiposity, determined by 3D measurements, was associated with overall survival (OS) (<i>p</i> = 0.04). At 3 years, the OS (95% CI) was 96% (93–100) in above-median adiposity patients and 86% (78–95) in below-median adiposity patients. Low lean body mass (LBM), assessed from the pretreatment PET-CT images using automatic Anthropometer3DNet software, may serve as a predictive marker for acute treatment-related toxicity in PMBL patients, particularly those receiving the dose-intensive R-ACVBP regimen. Additionally, depletion of the subcutaneous fat mass was correlated with an increased risk of mortality, highlighting the importance of a comprehensive BC assessment in this patient population.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144606568","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}