Hematological Oncology最新文献

{"title":"CLINICAL OUTCOMES AND PROGNOSTIC FACTORS IN NODAL AGGRESSIVE T-CELL LYMPHOMAS: INSIGHTS FROM 655 CASES REGISTERED IN THE T-CELL PROJECT 2.0","authors":"S. Luminari, L. Conte, N. Shokun, M. Civallero, G. Hapgood, M. Prince, E. Miranda, C. Chiattone, M. E. Cabrera, A. Pavlovsky, F. Hits, T. Skrypets, S. M. Rodriguez Pinilla, F. Francine, R. Advani, J. Vose, M. Federico","doi":"10.1002/hon.70094_388","DOIUrl":"https://doi.org/10.1002/hon.70094_388","url":null,"abstract":"<p>L. Conte, N. Shokun, M. Civallero, G. Hapgood, M. Prince, E. Miranda, C. Chiattone, M. E. Cabrera, A. Pavlovsky, F. Hits, T. Skrypets, S. M. Rodriguez Pinilla, F. Francine, R. Advani, and J. Vose equally contributing author.</p><p><b>Background:</b> According to the WHO classification of hematopoietic tissue tumors, the group of nodal aggressive T-cell lymphomas (TCLs) consists of PTCL-NOS, ALCL ALK-, AITL, and Nodal TCL with T-follicular helper phenotype. Despite advancements in therapeutic strategies, survival outcomes remain unfavorable. This study aims to evaluate the clinical characteristics, treatment patterns, and survival outcomes of patients diagnosed with nodal aggressive TCLs within the T-Cell Project 2.0, (clintrials.gov:03964480), an international prospective registry designed to improving the understanding of T-cell malignancies.</p><p><b>Methods:</b> A total of 655 patients diagnosed with nodal aggressive TCL between January 1, 2018, and June 30, 2023, were analyzed. Kaplan-Meier curves were used to estimate OS and PFS, while univariate and multivariate analyses identified prognostic factors.</p><p><b>Results:</b> The cohort included 312 patients with PTCL-NOS (47.6%), 172 with ALCL ALK- (26.3%), 158 with AITL (24.1%), and 13 with nodal TCL with TFH phenotype (1.9%). The median age was 60 yrs (19–93), with 59.7% males. The majority presented with stage III-IV (77.1%), 50.3% had B symptoms, 27.4% bone marrow involvement and 53.9% were EBV-positive.</p><p>The most frequent 1st line therapies were CHOEP (39.2%), CHOP/CHOP-like (30.8%) and BV-CHP. The CR rate was 49.0%, and PR 15.1%. Non-responders (NR) accounted for 35.9% of cases. The median follow-up was 26 months (95% CI: 22.4–29.6), with a 45.3% mortality rate.</p><p>The 2-yr OS and PFS rates were 50.8% and 36.1%, respectively. Patients achieving CR had significantly better survival outcomes, with a 2-yrs OS of 78.8% and PFS of 61.9%, while those with PR had a 2-yr OS of 34.8% and PFS of 21%. Of note, patients treated with BV-CHP showed a significantly better outcome (<i>p</i> < 0.001).</p><p>Univariate analysis identified age > 60 yrs (<i>p</i> < 0.001), stage III-IV (<i>p</i> < 0.001), ECOG ≥ 1 (<i>p</i> < 0.001), LDH > UNL (<i>p</i> < 0.001), hemoglobin < 12 g/dL (<i>p</i> < 0.001), platelets < 150 g/L (<i>p</i> < 0.001), albumin < 35 g/L (<i>p</i> = 0.01), histotype (ALCL- vs. PTCL-NOS or AITL: <i>p</i> < 0.001), IPI ≥ 2 (<i>p</i> < 0.001), and PIT ≥ 2 (<i>p</i> < 0.001) as significant negative prognostic factors for both OS and PFS.</p><p>In the multivariate analysis, histotype, age > 60 yrs, and stage III-IV emerged as independent prognostic factors for both OS and PFS (<i>p</i> < 0.001). Additionally, low PLT count was a significant independent predictor of worse PFS (<i>p</i> < 0.01).</p><p><b>Conclusions:</b> Nodal TCLs remain highly aggressive diseases with poor long-term survival. Patients with PCTL-NOS and AITL h","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_388","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144291840","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":"TAZEMETOSTAT PLUS AMDIZALISIB IN RELAPSED/REFRACTORY PERIPHERAL T-CELL LYMPHOMA PATIENTS WITH DIVERSE GENOMIC SIGNATURES: RESULTS FROM A PHASE 2 STUDY","authors":"S. Cheng, M. Cai, Z. Li, Y. Shuang, H. Wu, Q. Zhang, J. Ma, H. Zhou, Y. Li, K. Zhou, P. Li, W. Qian, W. Yang, S. Zhou, X. Jia, L. Jiao, J. Wangwu, X. Luo, C. Guan, D. Chen, S. Fan, M. M. Shi, W. Su, W. Zhao","doi":"10.1002/hon.70093_163","DOIUrl":"https://doi.org/10.1002/hon.70093_163","url":null,"abstract":"<p><b>Introduction:</b> Peripheral T-cell lymphomas (PTCL) are aggressive, heterogeneous T cell neoplasms lacking effective treatments. Patients (pts) with distinct gene signatures respond differently to therapies. Tazemetostat (TAZ) is the first enhancer-of-zeste-homolog-2 (EZH2) inhibitor approved by FDA in 2020. Amdizalisib is a novel and highly potent selective inhibitor of phosphatidylinositol 3-kinase p110δ isoform (PI3Kδ). This open label, single-arm, phase 2 trial (NCT05713110) evaluated the efficacy and safety of TAZ plus Amdizalisib in relapsed/refractory (R/R) lymphoma. Herein, we report the results in PTCL pts with genomic data.</p><p><b>Methods:</b> Pts with histologically confirmed R/R PTCL after at least one systemic therapy were eligible. TAZ 800 mg BID plus Amdizalisib 20 or 30 mg QD were administered orally until disease progression, intolerability, or withdrawal. The responses were assessed by investigators according to LUGANO 2014 criteria. Somatic gene alterations of tumor and blood samples were detected by next generation sequencing (NGS) (188-gene panel, Genetron).</p><p><b>Results:</b> Up to 31 Dec 2024, 29 PTCL pts were enrolled with median age of 61 years, 69.0% were male, 44.8% were stage IV and 20.7% with bone marrow involvement at baseline. Median prior systemic therapy lines were 3 (range 1–13), and 24 (82.8%) pts were refractory to the last regimen.</p><p>The overall response rate (ORR) was 60.7% (4 complete responses [CRs], 13 partial responses [PRs]) in 28 evaluable pts. The ORRs were 85.7% in angioimmunoblastic T cell lymphoma (AITL) (3 CRs, 9 PRs/14 evaluable pts), 25.0% in PTCL, not otherwise specified (2 PRs/8 evaluable pts), 100.0% in primary cutaneous anaplastic lymphoma kinase fusion-negative anaplastic large cell lymphoma (pcALK-ALCL) (1 CR, 1 PR/2 evaluable pts) and no response was observed in systemic ALK-ALCL pts (3 stable disease/3 evaluable pts). Median duration of response and progression-free survival were 6.47 and 8.25 months (m), respectively within a median follow-up of 10.97m. The overall survival has not been reached due to insufficient death events observed.</p><p>Genomic characteristics were assessed in 22 pts. <i>TET2</i> (55%) was the most prevalent mutation, followed by <i>PCLO</i> (32%), <i>HIST1H1E</i> (27%), <i>CSMD1</i> (23%), and <i>RHOA</i> (23%). ORR of 100% was observed in 5 pts with <i>TET2</i> and <i>RHOA</i> co-mutations. <i>CSMD1</i> and <i>RHOA</i> mutations were mutually exclusive. <i>CSMD1</i> alteration was associated with low ORR of 20%.</p><p>Median drug administration duration was 7.33m for 29 pts. Most pts (96.6%) experienced at least one treatment-related adverse event (TRAE), including 48.3% ≥ grade 3. The most common (> 10%) grade ≥ 3 TRAEs were neutropenia (24.1%), anaemia (17.2%), lymphopenia (13.8%), and thrombocytopenia (13.8%). No treatment-related death occurred.</p><p><b>Conclusions:</b> TAZ plus Amdizalisib has shown favorable responses in R/R PTCL, especi","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_163","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144291882","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":"IBRUTINIB-RITUXIMAB VERSUS PLACEBO-RITUXIMAB IN PATIENTS WITH PREVIOUSLY UNTREATED FOLLICULAR LYMPHOMA (FL): PRIMARY ANALYSIS OF THE PHASE 3 PERSPECTIVE STUDY","authors":"D. Belada, F. P. Gardner, A. C. de Oliveira, J. Sancho, E. Lomaia, D. Wright, M. Turgut, E. Martynova, Z. Lázár, B. Anz, M. Wang, W. Legiec, S. Opat, J. Pailden, H. M. Peltier, E. Marturano, J. P. Dean, I. W. Flinn","doi":"10.1002/hon.70093_26","DOIUrl":"https://doi.org/10.1002/hon.70093_26","url":null,"abstract":"<p><b>Introduction:</b> Single-agent rituximab (R) is indicated as first-line treatment for patients (pts) with FL who are ineligible for chemoimmunotherapy (CIT). In a phase 2 trial, ibrutinib (Ibr) plus R showed promising activity in pts with FL. Here, we report primary analysis results from the multinational, randomized, double-blind, phase 3 PERSPECTIVE study (NCT02947347) comparing Ibr-R versus placebo (Pbo) plus R in pts with previously untreated FL not eligible for CIT due to age and/or comorbidities.</p><p><b>Methods:</b> Eligible pts were ≥ 70 y, or 60–69 y with ≥ 1 comorbidity, and met ≥ 1 Groupe d'Etude des Lymphomes Folliculaires criterion for treatment. Pts were randomly assigned 3:1 to receive oral Ibr (560 mg) or Pbo once daily until progressive disease. All pts received R 375 mg/m<sup>2</sup> weekly for 4 wk then every 8 wk for up to 12 cycles. Randomization was stratified by age (60–69 years vs. ≥ 70 years), FLIPI-1 score (low vs. intermediate/high), and ECOG PS (0–1 vs. 2). The primary endpoint was progression-free survival (PFS) by investigator (INV) assessment per Cheson 2014 criteria using FDA censoring rules. PFS sensitivity analyses included PFS by independent review committee (IRC) assessment and use of global censoring rules. Secondary endpoints included overall response rate (ORR) by INV, overall survival (OS), infusion-related reaction (IRR) rates, and safety.</p><p><b>Results:</b> In total, 445 pts were assigned to receive Ibr-R (<i>n</i> = 334) or Pbo-R (<i>n</i> = 111). At baseline, median age was 74 y versus 75 y, 66% versus 67% had FLIPI-1 score ≥ 3, and 75% versus 76% had ECOG PS 0–1, respectively. At data cutoff, all pts had completed R treatment; Ibr or Pbo treatment was ongoing in 20% and 22% of pts, respectively. With a median time on study of 53.8 mo, PFS was significantly improved with Ibr-R versus Pbo-R (hazard ratio [HR], 0.71 [95% CI 0.53–0.96]; <i>p</i> = 0.02; median 42.0 vs. 32.8 mo) per INV with FDA censoring rules and with consistency in sensitivity analyses (Figure). ORR was 81% versus 68% with Ibr-R versus Pbo-R (rate ratio 1.19 [95% CI 1.04–1.36]; <i>p</i> = 0.004) and 4-y OS rates were 67% versus 71% (HR 1.12 [95% CI 0.77–1.63]; <i>p</i> = 0.55). IRRs occurred in 21% versus 27% of pts with Ibr-R versus Pbo-R. Median overall treatment duration was 22.1 mo with both Ibr-R and Pbo-R. Grade ≥ 3 AEs occurred in 78% versus 57% of pts; the most frequent grade ≥ 3 AEs were neutropenia (16% versus 7%), pneumonia (9% vs. 5%), hypertension (8% vs. 5%), COVID-19 (6% vs. 2%), COVID-19 pneumonia (6% vs. 3%), and diarrhea (6% vs. 2%); atrial fibrillation occurred in 5% versus 2%. Primary causes of death included AEs (14% vs. 7%) and FL (7% vs. 9%). 327 pts (73%) received study treatment during the pandemic; COVID-19-related death occurred in 9% of pts in the Ibr-R arm and 7% in the Pbo-R arm.</p><p><b>Conclusions:</b> In pts with previously untreated FL for whom R monotherapy is appropriate, addition of Ibr led","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_26","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292271","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":"AN IN VIVO PIGGYBAC INSERTIONAL MUTAGENESIS SCREEN TO SEARCH FOR MODIFIERS OF Myd88L265P-DRIVEN DLBCL LYMPHOMAGENESIS","authors":"S. Höfmann, A. Tabatabai, R. Flümann, S. Klein, I. Kisis, R. Öllinger, M. Möllmann, M. Hartnack, S. Kesper, A. Arora, B. v. Tresckow, R. D. Jachimowicz, R. Rad, G. Knittel, H. C. Reinhardt","doi":"10.1002/hon.70094_186","DOIUrl":"https://doi.org/10.1002/hon.70094_186","url":null,"abstract":"<p><b>Introduction:</b> Based on genetic features, human DLBCL cases can be subdivided into several distinct clusters. Recurrent mutations in <i>MYD88</i>, <i>CD79B</i>, <i>PRDM1</i> and frequent <i>BCL2</i> copy number gains are characteristic of the MCD/C5 cluster. Mice with B cell-specific expression of <i>Myd88</i><sup><i>L252P</i></sup> (orthologous to human p.L265P) develop a lymphoproliferative phenotype at old age and occasional lymphoma. We aimed to identify genes cooperating with <i>Myd88</i><sup><i>p.L252P</i></sup> in DLBCL lymphomagenesis by performing an <i>in vivo piggyBac</i> (<i>PB</i>) insertional mutagenesis screen.</p><p><b>Methods:</b> We crossed the <i>PB</i> transposon system with the <i>Myd88</i><sup><i>cond_p.L252P</i></sup> allele. Both the <i>PB</i> system and expression of <i>Myd88</i> p.L252P were activated B cell-specifically with <i>Cd19</i><sup><i>Cre</i></sup>. Animals were aged and samples were collected when mice became moribund. The isolated tumors were characterized immunohistochemically and transcriptionally. The malignant nature was verified by B cell receptor clonality analysis. Lastly, common transposon integrations were identified by QiSeq and subsequent bioinformatic analysis.</p><p>One of the most prominent hits from this screen was <i>Etv6</i>, which is commonly affected by deleterious mutations in MCD/C5 DLBCL. To investigate the role of <i>ETV6</i> in B cell biology and lymphomagenesis, we utilized an <i>Etv6-</i>flox allele in combination with <i>Cd19</i><sup><i>Cre/wt</i></sup>. Changes in the B cell compartment were determined by flow cytometry in steady state and after immunization. Cohorts were aged and developing lesions were characterized histologically and transcriptionally.</p><p><b>Results:</b> The presence of the <i>PB</i> system on the <i>Myd88</i><sup><i>L252P</i></sup> background reduced overall survival. <i>Myd88</i>/<i>PB</i> mice formed clonal B220<sup>+</sup> lymphomas. We were able to identify ∼1000 genes with significantly enriched integrations. Reminiscent of MCD DLBCL, hits were strongly enriched for the KEGG gene set ‘B cell receptor signaling’. Furthermore, we observed a distinct overlap between the <i>PB</i> hits and genes mutated in MCD DLBCL, including <i>Tbl1xr1</i>, <i>Pim1</i> and <i>Etv6</i>. To investigate the effects of a B cell-specific loss of <i>Etv6</i>, we crossed a conditional knockout-allele to <i>Cd19</i><sup><i>Cre</i></sup>. Germinal center (GC) B cells were increased in 30wks old unimmunized <i>Etv6</i>-KO animals compared to <i>Cd19</i><sup><i>Cre</i></sup> controls. In contrast, post-GC species were reduced in <i>Etv6</i>-KO. Unexpectedly, the number of NP-specific GCB cells was lower in the <i>Etv6</i>-KO cohort ten days after NP-OVA immunization. To assess the lymphomagenic potential of <i>Etv6</i> loss in a <i>Myd88</i>-mutant setting, we generated <i>Myd88</i><sup><i>p.L252P</i></sup> animals with or without <i>Etv6</i>-KO. Indeed, <i>Etv6</i>-KO resu","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_186","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292416","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":"MOLECULAR FEATURES ENCODED IN THE DYNAMIC ctDNA MONITORING REVEAL PROGNOSTIC VALUE, DIFFERENT CLINICAL COURSES AND CLONE EVOLUTION FOR DIFFERENT GENETIC SUBTYPES OF DLBCL","authors":"J. Liang, Y. Wu, W. Xu","doi":"10.1002/hon.70094_422","DOIUrl":"https://doi.org/10.1002/hon.70094_422","url":null,"abstract":"<p><b>Introduction:</b> The ctDNA-based minimal residual disease (MRD) status at the end of treatment (MRD<sup>end</sup>) has been demonstrated as even stronger prognostic marker in both clinical trial and the real-world population for DLBCL patients (pts). However, no data has been shown (i) The clinical course embedded in the different genetic subtypes of DLBCL, (ii) Clonal evolution possessed in serial tissue and plasma samples.</p><p><b>Methods:</b> We enrolled 164 DLBCL pts from our center undergoing first line (1L) therapy for ctDNA profiling at 2 pre-defined milestones (matched baseline and end of treatment (EOT) plasma samples) using a 475 gene lymphoma-specific sequencing panel which had been detailed decribed in our previous work (<i>Jinhua Liang, Leukemia</i>). By the last visit in December 2024, the median follow-up duration was 25.4 (range, 14.9−43.7) months. All pts received R-CHOP regimens.</p><p><b>Results:</b> Among the 164 pts, the median age was 57 years, 57.3% had stage III−IV disease and 42.1% had IPI scores 3−5. Among the 164 pts, 46 pts (28.1%) were defined as MRD<sup>end</sup> positivity (MRD<sup>end+</sup>) (Figure 1A). The LymphGen subtype classification according to plasma and tissue were shown in Figure 1B. The MRD<sup>end− </sup>ratio in different genetype was shown in Figure 1C. EOT-MRD status is associated with worse PFS and OS (<i>p</i> < 0.001). Among the EOT-CR patients (<i>N</i> = 131), MRD<sup>end+</sup> pts had trend towards worse PFS (<i>p</i> = 0.069) (Figure 1D-E). After analyzing the disease course of all pts according to the genetic subtypes, we found that the clinical problem for TP53 disruption pts is primary refractory, rather than relapse. However, MCD subtype that has poor prognosis because of a persistent high risk of relapse despite reaching CR while the clinical problem for BN2 pts is primary refractory and high rate of relapse (Figure 1F). MRD<sup>end</sup> negativity was unstable and prone to relapse for BN2 and MCD subtype patients (Figure 1G<b>)</b>. The EOT top gene alterations (GAs) for MRD<sup>end+</sup> pts was TP53<sup>mut</sup> (34.8%) which were significantly different from baseline plasma mutation profiling (Figure 1H). Firstly, we found that most EOT GAs for the MRD<sup>end+</sup> pts were the predominant gene at baseline according the serial plasma samples (Figure 1I). However, 37 pts had additional GAs (Figure 1J) which were enriched in cell differentiation, cell cycle and TP53 disruption pathways (Figure 1L) in PD plasma samples in comparison with pretreatment plasma samples and the detailed number were shown in Figure 1K. Among the 38 pts of TP53<sup>mut</sup>, 18 pts were MRD<sup>end+ </sup>(47.4%); among these 18 MRD<sup>end+</sup> pts, TP53<sup>mut</sup> was not cleared in 11 pts (61.1%) (Figure 1M). </p><p><b>Conclusions:</b> These data demonstrate that: (i) Different clinical courses were shown in different genetic subtypes for further personalized subtype-specific clinica","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_422","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292475","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":"PROGNOSTIC VALUE OF 18F-FDG PET/CT VOLUMETRIC PARAMETERS IN CHILDHOOD, ADOLESCENT, AND YOUNG ADULT HODGKIN LYMPHOMA: A SYSTEMATIC REVIEW FROM THE SEARCH GROUP","authors":"C. Gowdy, J. Flerlage, J. Seelisch, M. Palese, T. Bradshaw, S. M. Castellino, S. Cho, K. Dieckmann, B. S. Hoppe, S. Howard, K. Kelly, L. Kurch, H. Lai, E. Lopci, J. Lucas, C. Mauz-Körholz, K. McCarten, N. Pandit-Taskar, H. Schöder, J. Steglich, D. Stoevesandt, S. Voss, S. Milgrom","doi":"10.1002/hon.70094_373","DOIUrl":"https://doi.org/10.1002/hon.70094_373","url":null,"abstract":"<p>C. Gowdy, J. Flerlage, J. Seelisch, M. Palese, T. Bradshaw, S. M. Castellino, S. Cho, K. Dieckmann, B. S. Hoppe, S. Howard, K. Kelly, L. Kurch, H. Lai, E. Lopci, J. Lucas, C. Mauz-Körholz, K. McCarten, N. Pandit-Taskar, H. Schöder, J. Steglich, D. Stoevesandt, and S. Voss equally contributing author.</p><p><b>Introduction:</b> In adults with classic Hodgkin lymphoma (cHL), PET volumetric parameters, such as metabolic tumor volume (MTV), are valuable for risk stratification. This study was undertaken to explore the role of metabolic parameters in children, adolescents, and young adults with cHL.</p><p><b>Methods:</b> This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. Five databases were searched on 16th October 2024: MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCO), EBM Reviews (OVID) and the Web of Science Core Collection. Eligible studies were peer-reviewed manuscripts, written in English, published from database inception to the search date that included patients up to 21 years of age with a diagnosis of cHL and a <sup>18</sup>F-FDG PET/CT scan with calculation of MTV. Two authors independently reviewed all studies identified in the literature search.</p><p><b>Results:</b> The search strategy detected 3669 studies from which 1085 duplicates and 2584 studies were excluded following 2-person review of titles and abstracts. Full-text review of 81 papers identified 35 as eligible for inclusion. Fifteen of the papers (43%) evaluated a cohort exclusively < 21 years of age and 20 papers (57%) considered children and adults, with a median of 69 (21–297) participants. All 8 studies that explored the association of baseline MTV and/or TLG (total lesion glycolysis) with known risk factors (ex. bulk, stage, clinical parameters used to define treatment group/level) identified a significant correlation. Twelve papers explored the association of baseline MTV and/or TLG with disease response on PET/CT according to Lugano criteria, of which 9 (75%) demonstrated a statistically significant correlation. Twenty papers explored the association of baseline PET parameters with clinical outcome (ex. overall survival, progression-free survival) and 15 (75%) demonstrated an independent statistically significant correlation. Of 6 studies that explored higher-order radiomic features, 4 (67%) found that they out-performed MTV and/or TLG. Thirty-three of 35 studies detailed the segmentation approach that was used to delineate disease, of which 11 used or recommended an absolute fixed threshold method.</p><p><b>Conclusions:</b> Metabolic PET parameters are valuable for risk stratification; the review has found heterogeneity of results related to differences in patient cohorts, treatment strategies, methods for disease segmentation, and parameter calculation. This group of international experts will provide recommendations regarding the necessary next steps to harmonize the approach and ","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_373","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292478","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":"CHIDAMIDE IN COMBINATION WITH AZACITIDINE, MITOXANTRONE LIPOSOMES, AND PREDNISONE (CAMP REGIMEN) FOR TREATMENT-NAÏVE TFH-DERIVED PERIPHERAL T-CELL LYMPHOMA","authors":"H. Liu, W. Liu, W. Huang, L. Qiu, D. Zou","doi":"10.1002/hon.70094_392","DOIUrl":"https://doi.org/10.1002/hon.70094_392","url":null,"abstract":"<p><b>Objective:</b> Peripheral T-cell lymphoma (PTCL) is a rare but challenging malignancy, in which the TFH (T follicular helper)-derived PTCL subtype has a poor prognosis and limited treatment options. In this study, chidamide in combination with azacitidine, mitoxantrone liposomes and prednisone (CAMP regimen) was used for the treatment of treatment-naïve TFH-derived peripheral T-cell lymphoma, aiming to evaluate the efficacy and safety of this treatment regimen and provide a new treatment option for clinical practice.</p><p><b>Methods:</b> This study is a multicenter, prospective phase II clinical trial (clinical trial ID: IIT2023003), the main purpose of which is to investigate the safety and preliminary efficacy (ORR rate) of chidamide in combination with azacitidine, mitoxantrone liposome and prednisone (CAMP regimen) in the treatment of treatment-naïve TFH-derived PTCL. Eligible treatment-naïve TFH-derived PTCL patients were included in the program who received CAMP regimen combination therapy, the specific regimen was: chidamide 30 mg/day orally, biw; azacitidine 75 mg/m<sup>2</sup> subcutaneously, d1-d7; mitoxantrone liposome 16 mg/m<sup>2</sup> d1; prednisone 60 mg/m<sup>2</sup>, d1–5; 28 days is a cycle of treatment. Patients who achieve CR/PR after four-six cycles could choose to undergo autologous hematopoietic stem cell transplantation, followed by chidamide maintenance therapy for 2 years.</p><p><b>Results:</b> A total of 13 treatment-naïve patients with TFH-derived PTCL were enrolled, of whom 46% were male, with a median age of 61 (39–70) years, 92% of whom had Ann Arbor stage III-IV, 31% of the patients had B symptoms, 69% of the patients had extranodal involvement, and 54% of the patients were EBER-positive. 46% of patients were IPI score 3, and 62% of patients were PIT score ≥ 2. The median number of treatment courses was 4 (4–7), and 3 patients (23%) underwent autologous hematopoietic stem cell transplantation, with a complete response (CR) rate of 100% and an overall best objective response rate (ORR) of 100%. At a median follow-up of 7 (4–12) months, with a median PFS of 7 (4–12) months, two patients (15%) experienced disease progression and one patient died due to disease progression. During CAMP regimen therapy, 6 patients (46%) developed grade 1–2 myelosuppression, which could be recovered after supportive therapy. Four patients (31%) developed pulmonary or urinary tract infections and were cured with active anti-infective therapy.</p><p><b>Conclusion:</b> Chidamide combined with azacitidine, mitoxantrone liposome and prednisone (CAMP regimen) in the treatment of treatment-naïve TFH-derived PTCL has a high complete response rate and a controllable safety profile, which is expected to become a new treatment option for treatment-naïve TFH-derived PTCL, but the cohort needs to be further expanded to verify its safety and efficacy.</p><p><b>Research</b> <b>funding declaration:</b> Clinical and translational medicine researc","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_392","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292484","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":"AN EXPLAINABLE ARTIFICIAL INTELLIGENCE mDELRelapseNet MODEL TO PREDICT RELAPSE IN DIFFUSE LARGE B-CELL LYMPHOMA BASED ON THE SPATIAL ORGANIZATION OF MYC+BCL2+BCL6− Cells","authors":"S. Sridhar, K. Gupta, M. M. Hoppe, F. Shuangyi, Y. Peng, S. De Mel, M. L. Poon, C. K. Ong, S. T. Lim, C. Nagarajan, N. F. Grigoropoulos, J. D. Khoury, D. W. Scott, W. J. Chng, Y. L. Chee, S. Ng, C. Tripodo, A. D. Jeyasekharan","doi":"10.1002/hon.70094_204","DOIUrl":"https://doi.org/10.1002/hon.70094_204","url":null,"abstract":"<p><b>Introduction:</b> The overexpression of MYC and BCL2 categorizes diffuse large B-cell lymphoma (DLBCL) termed double-expressor lymphoma (DEL) with worse survival after chemoimmunotherapy. The clinical utility of DEL is limited by controversy in cut-offs for positivity of these markers, and a possible protective effect of BCL6 expression. Using single-cell resolved imaging, we showed (Hoppe et al., <i>Cancer Discovery</i> 2023) that survival is robustly associated with the fraction of malignant cells that co-express the oncogenes MYC and BCL2 in the absence of BCL6 (M+2+6−), refining the DEL definition. Here we present a follow up study evaluating the clinical significance of the spatial distribution of M+2+6− cells, and its potential clinical applicability through an XAI model “mDELRelapseNet”.</p><p><b>Methods and Results:</b> M+2+6− cells display non-random spatial organization within a tumour. To evaluate the significance of these patterns, we employed Geyers point process analyses- a method widely used in ecology and geography- to understand the spatial distribution of M+2+6− cells within DLBCL using x-y coordinate information from multiplexed fluorescent immunohistochemistry (mfIHC) images. Cases could be divided into two groups based on these: one with “clustered” and another with “dispersed” M+2+6− cell distribution. Interestingly, cases with “dispersed” pattern of M+2+6− cells consistently had shorter survival in all analyzed cohorts (<i>p</i> < 0.05 in 4 independent cohorts; <i>N</i> = 449 patients), the first description to our knowledge that the spatial organization of a subset of tumour cells influences clinical outcomes in cancer.</p><p>We then aimed to harness this spatial information from MYC, BCL2 and BCL6 staining to develop an XAI model to predict for relapse in DLBCL. A challenge however was the lack of versatile analysis tools to handle diverse image formats and marker combinations. We addressed this by developing a unified ground-up deep learning model “mDELRelapseNet”; to accept any standard image format with any combination of these markers, eliminating the need for specialized tools for each scenario. Our model achieved a validation accuracy of 70% and was trained on mfIHC and pseudo IHC images from two DLBCL cohorts (<i>n</i> = 253) and validated on a third (<i>n</i> = 18). Through backtracking, we saw that the early layers learnt from M+2+6− hotspots for prediction. We refined the model by providing the cell of origin classification, as we noted dispersed M+2+6− cells to be enriched in ABC DLBCL. This improved performance to 94.8% validation accuracy in ABC and 94.1% in GCB DLBCL.</p><p><b>Conclusions:</b> We show that survival in DLBCL is linked not only to the numbers of M+2+6− cells but also their spatial organization. We created a web app (https://mdel-relapse-net.streamlit.app) that uses histopathological images of MYC/BCL2/BCL6 to identify DLBCL at high risk of R-CHOP failure, with potential applicability ","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_204","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292576","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":"DURABLE EFFICACY WITH FIXED-DURATION EPCORITAMAB + POLATUZUMAB, VEDOTIN, RITUXIMAB, CYCLOPHOSPHAMIDE, DOXORUBICIN, AND PREDNISONE (POLA-R-CHP) FOR 1L DLBCL (EPCORE NHL-5)","authors":"D. Lavie, D. A. Kerr, A. Avigdor, I. Avivi, D. Belada, P. Abrisqueta, K. Izutsu, C. Grande-Garcia, S. Yeh, H. Goto, M. Seliem, S. R. Siddani, N. Joshi, B. Noorani, N. Dixit, S. Diness Vindelov, P. Jafarinasabian, C. Thieblemont","doi":"10.1002/hon.70094_282","DOIUrl":"https://doi.org/10.1002/hon.70094_282","url":null,"abstract":"<p><b>Introduction</b>: First-line (1L) standard of care for diffuse large B-cell lymphoma (DLBCL) is R plus C, H, vincristine, and P (R-CHOP), and it continues to evolve with pola-R-CHP showing higher complete response rates (CRR) of 78% and longer progression-free survival than R-CHOP (Tilly 2022), However, additional therapies are needed to further improve cure rates for 1L patients (pts). Epcoritamab (epcor) is a subcutaneous CD3×CD20 bispecific antibody approved globally as a monotherapy for 3L+ R/R DLBCL with demonstrated safety and efficacy in combination with 1L R-CHOP and pola-R-CHP (CRRs, 87% [Falchi 2024] and 89% [Lavie 2024], respectively). Here we report 16.1 months (mos) follow-up data from the epcor + pola-R-CHP cohort of the Phase 1b/2 EPCORE NHL-5 (NCT05283720) study.</p><p><b>Methods</b>: Pts with newly diagnosed CD20+ DLBCL, ECOG PS 0–2, and IPI score 2–5 received 21-day (d) cycles (c) of epcor + pola-R-CHP for 6 c, then 2 c of epcor monotherapy. Two step-up dosing of epcor was used in c1, followed by QW dosing during c2-4 and Q3W during c5-8. Corticosteroids were given during c1 to further mitigate cytokine release syndrome (CRS) with epcor. G-CSF or pegylated G-CSF was administered 1–2 d after administration of H, C, and pola during c1–6. Key endpoints included investigator-assessed response rate (ORR/CRR), time to response (TTR/TTCR), and safety; exploratory endpoints included biomarkers and pharmacokinetics (PK).</p><p><b>Results</b>: As of Oct 1, 2024, 37 pts received epcor + pola-R-CHP. Median age was 64 years and 51% were female; 34 had DLBCL NOS, 1 high-grade B-cell lymphoma, and 2 follicular lymphoma; 54% had GCB disease and 43% non-GCB; 19% had IPI2, 25% had bulky disease. Median follow-up was 16.1 mos (95% CI: 11.1, 16.6). Among 35 response-evaluable pts, ORR was 100% (97% CRR [Table]) with similar findings across subgroups. Median TTR and TTCR were 2.7 mos (range: 1.3–3.3) and 2.8 mos (range: 1.3–10.9), respectively. Tx-emergent AEs (TEAEs) are summarized (Table). Three (8%) pts discontinued epcor and 2 (5%) discontinued pola-R-CHP due to an AE. The most common G3/4 AEs were neutropenia (65%), anemia (19%), and leukopenia (11%). One pt had a fatal TEAE (urosepsis) not considered related to epcor. Low-grade CRS occurred in 51% of pts (35% G1, 16% G2, no G3+), with expected onset primarily after the first full dose of epcor (C1D15). All CRS events resolved, with median resolution time of 2 d (range: 1–6). No ICANS was observed. PK and biomarker data will be presented later.</p><p><b>Conclusions</b>: Fixed-duration epcor + pola-R-CHP with follow-up of 16.1 mos in pts with newly diagnosed DLBCL continues to show high ORR and CRR across all subgroups with no new safety signals. Data continue to support that adding epcor to 1L SOC drives deep and durable responses. CRS was low-grade with predictable timing of onset. These data reaffirm prior findings, demonstrate the versatility of subcutaneous epcor, and support the pote","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_282","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292638","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":"PROGNOSTIC VALUE OF CIRCULATING TUMOR DNA IN PATIENTS WITH ADVANCED STAGE CLASSIC HODGKIN LYMPHOMA TREATED ON SWOG S1826","authors":"J. Paczkowska, M. Kaszkowiak, M. LeBlanc, C. Stewart, A. F. Herrera, J. C. Fernando del Castillo, S. M. Castellino, S. C. Rutherford, A. M. Evens, K. Davison, H. Li, D. Neuberg, M. Murakami, J. Makker, B. Kahl, J. P. Leonard, N. L. Bartlett, S. M. Smith, J. Y. Song, K. M. Kelly, G. Getz, J. W. Friedberg, M. A. Shipp","doi":"10.1002/hon.70093_21","DOIUrl":"https://doi.org/10.1002/hon.70093_21","url":null,"abstract":"<p>J. Paczkowska, M. Kaszkowiak, M. LeBlanc, C. Stewart, A. F. Herrera, G. Getz, J. W. Friedberg, M. A. Shipp equally contributing author.</p><p><b>Background:</b> S1826 demonstrated that incorporation of nivolumab into initial chemotherapy (N-AVD) improved progression-free survival (PFS) compared with Bv-AVD. In this pre-planned analysis, we assessed the prognostic value of serial circulating tumor DNA (ctDNA) detection in S1826 using a newly developed assay.</p><p><b>Methods:</b> Pts were ≥ 12 years (y) with stage 3–4 cHL. Serial plasma samples from first 388 pts and paired germline DNAs were evaluated with a targeted sequencing panel that included recurrently mutated genes (single nucleotide variants and indels), somatic copy number alterations, and structural variants in cHL; and probes to detect sites of physiologic and aberrant somatic hypermutation and determine EBV status. Duplex read sequencing was employed to enhance error suppression and recurrent mutations, SCNAs and SVs were detected using computational algorithms optimized for ctDNA analysis. A newly developed computational pipeline, MTB-Tracker, was used to identify clustered SNVs and assess treatment-related changes in molecular tumor burden (MTB), reflected as log-fold changes in haploid genome equivalents per milliliter of plasma (hGE/mL) over time.</p><p><b>Results:</b> 375/388 (97%) had detectable clustered SNVs at baseline and were included in the MTB analysis. The baseline clinical characteristics of these pts mirrored the overall S1826 population: median age 25 years (range, 12–83 years), 28% < 18 years, 10% > 60 years, 37% with IPS 4–7; 191 pts received N-AVD (2 years PFS 91%);184 pts received BV-AVD (2 years PFS 81%). Baseline MTB correlated with clinical features including IPS score (0–3 vs. 4–7, <i>p</i> < 0.0001) and B symptoms (<i>p</i> < 0.0001) in all analyzed pts. MTB at C3D1 was prognostic for outcome in the full cohort; undetectable ctDNA at C3D1 was associated with 2 years PFS 91% versus 2 years PFS 64% in the ctDNA<sup>+</sup> group, <i>p</i> < 0.0001. Similar results were observed within each treatment arm at C3D1 (N-AVD: ctDNA<sup>−</sup> 2 years PFS 95% versus ctDNA<sup>+</sup>, 74%; BV-AVD: ctDNA<sup>−</sup> 2 years PFS 88% versus ctDNA<sup>+</sup> 53%, both <i>p</i> < 0.0001). Dynamic assessment of the changes in MTB between baseline and C3D1 allowed further discrimination of low and higher risk groups (Figure). In comparison to pts with undetectable ctDNA at C3D1, pts with a > median (3.64) log fold drop in MTB at C3D1 had slightly less favorable outcomes: 2 years PFS in all, N-AVD and BV-AVD pts of 87%, 88% and 86%, respectively. In contrast, pts with < median log-fold drop at C3D1 had significantly inferior outcomes: 2 years PFS in all, N-AVD and BV-AVD pts of 41%, 59% and 25%, all <i>p</i> < 0.0001. The presence versus absence of detectable ctDNA at EOT was also significantly associated with PFS (ctDNA<sup>−</sup>, 2 years PF","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_21","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292662","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}