Hematological Oncology最新文献

{"title":"IMPACT OF EBV STATUS AND HISTOLOGY ON OUTCOMES WITH NIVOLUMAB-AVD VERSUS Bv-AVD IN PATIENTS ENROLLED ON SWOG S1826","authors":"S. Ahmed, H. Li, A. F Herrera, A. Perry, A. E Kovach, K. Davison, S. C Rutherford, S. Castellino, A. Evens, B. Kahl, N. Bartlett, J. P Leonard, M. A Shipp, S. M Smith, K. Kelly, M. LeBlanc, J. W Friedberg, J. Y Song","doi":"10.1002/hon.70093_20","DOIUrl":"https://doi.org/10.1002/hon.70093_20","url":null,"abstract":"<p><b>Introduction:</b> Historically, survival rates in patients (pts) with Epstein-Barr virus (EBV)-positive (+) classic Hodgkin lymphoma (cHL) are lower than EBV− pts, in part due to increased frequency in older pts. EBV itself directly leads to increased PD-L1 expression in cHL, in addition to chromosome 9p24.1 alterations and the tumor microenvironment. This subset analysis from the S1826 trial which evaluated N-AVD versus Bv-AVD in newly diagnosed advanced-stage cHL assesses the impact of EBV status and histology on treatment outcomes.</p><p><b>Methods:</b> Eligible pts with stage III–IV cHL had histology confirmed by central pathology review (nodular sclerosis (NS) versus non-NS subtypes: mixed cellularity, lymphocyte-rich/depleted) and reported EBV status (IHC or ISH). Pts were randomized 1:1 to 6 cycles of N-AVD or Bv-AVD. The primary endpoint was progression-free survival (PFS).</p><p><b>Results:</b> Of 994 pts enrolled, 522 pts (53%) had available EBV status (EBV+ = 101; EBV− = 421). Among the 254 pts randomized to N-AVD, 48 (19%) were EBV+ and 206 were EBV-. Amongst 268 pts randomized to Bv-AVD, 53 (20%) were EBV+ and 215 were EBV-. Median age was 42 years (range 12–83) in EBV+ pts versus 25 years (range 12–80) in EBV− pts (<i>p</i> < 0.0001). EBV+ pts had higher IPS scores but no statistical difference in stage or B symptoms.</p><p>With median follow-up of 24 months, within EBV− group, PFS was longer with N-AVD (HR 0.54; <i>p</i> = 0.0306); 2-year PFS of 92% (95% CI: 87–95) versus 85% (95% CI: 79–89) for Bv-AVD. In the EBV+ group, PFS was dramatically improved with N-AVD (HR 0.27; <i>p</i> = 0.0127); 2-year PFS of 95% (95% CI: 80–99) in N-AVD and 72% (95% CI: 58–83) in Bv-AVD. Among EBV+ patients, the treatment effect with N-AVD remained significant after adjusting for age groups (HR = 0.25; <i>p</i> = 0.0144). In N-AVD arm, no PFS difference was seen between EBV+ and EBV− (95% versus 92%; <i>p</i> = 0.88) but in Bv-AVD arm EBV+ pts had poorer PFS (72% versus 85%; <i>p</i> = 0.03).</p><p>102 pts had non-NS histology (N-AVD = 55; Bv-AVD = 47), median age 48 years versus 22 years for NS (<i>p</i> < 0.0001), and 30% non-NS were > 60 years versus 4% of NS pts > 60 years. In non-NS pts, N-AVD resulted in longer PFS (HR 0.31; 95% CI: 0.31–0.74; <i>p</i> = 0.005), 2-year PFS of 92% (95% CI: 79–97) versus 65% (95% CI: 50–77) for Bv-AVD. NS pts had longer PFS with N-AVD (HR 0.49; 95% CI: 0.28–0.86; <i>p</i> = 0.01): 2-year PFS of 94% (95% CI: 90–96) versus 87% (95% CI: 83–91). In N-AVD arm, PFS was not significantly different in non-NS 2 years PFS 92% versus 94% in NS pts (HR 2.01, <i>p</i> = 0.11). In Bv-AVD arm, non-NS pts had inferior PFS (HR = 3.4, <i>p</i> < 0.0001), 2 years PFS 65% versus 87% in NS.</p><p><b>Conclusions:</b> While N-AVD improves outcomes for advanced stage cHL in all pts irrespective of EBV status or histologic subtype, it substantially abrogated the historically poor outcomes in pts with EBV+ cHL and thos","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_20","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300096","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":"MINIMAL RESIDUAL DISEASE WITH BENDAMUSTINE-RITUXIMAB WITH OR WITHOUT ACALABRUTINIB IN PATIENTS WITH PREVIOUSLY UNTREATED MANTLE CELL LYMPHOMA: RESULTS FROM THE ECHO TRIAL","authors":"P. L. Zinzani, S. Spurgeon, M. Pavlovsky, C. Y. Cheah, D. Villa, S. Luminari, V. Otero, G. De Jesus, R. Lesley, M. L. Wang","doi":"10.1002/hon.70093_136","DOIUrl":"https://doi.org/10.1002/hon.70093_136","url":null,"abstract":"<p><b>Introduction:</b> The combination of acalabrutinib with bendamustine-rituximab (ABR) significantly improved progression-free survival (PFS) versus placebo with BR (PBR) in the phase 3 ECHO trial (NCT02972840) in older patients (pts) with previously untreated mantle cell lymphoma (MCL) (Wang M, et al. <i>EHA</i> 2024. Abstract #LB3439). Minimal residual disease (MRD) has been shown to be an impactful prognostic factor for outcomes in MCL. Previously presented data from the trial showed that a lower percentage of pts receiving ABR had molecular relapse during the maintenance period than pts receiving PBR (Dreyling M, et al. <i>Blood</i>. 2024;144(Suppl 1):1626). Herein, we examine the association between MRD status and clinical outcomes in the ECHO trial.</p><p><b>Methods:</b> Pts aged ≥ 65 years with previously untreated MCL and Eastern Cooperative Oncology Group performance status ≤ 2 were randomly assigned 1:1 to receive ABR or PBR. BR was given for 6 cycles (induction) followed by rituximab maintenance for 2 years in pts achieving a partial or complete response (CR). Acalabrutinib (100 mg twice daily) or placebo was administered until disease progression or unacceptable toxicity. Crossover to acalabrutinib was permitted at disease progression. The primary endpoint was PFS per independent review committee. MRD (10<sup>−5</sup>) was assessed in peripheral blood every 24 weeks and at CR or progressive disease using the ClonoSEQ assay (Adaptive Biotechnologies).</p><p><b>Results:</b> At the February 15, 2024 data cutoff, 266 pts in the ABR arm and 252 pts in the PBR arm were evaluable for MRD (89.0% and 84.3%, respectively). Pts who did not achieve MRD negativity at any time had a median PFS and overall survival (OS) of 13.8 and 22.8 months, respectively, while pts achieving MRD negativity had a median PFS of 66.7 months (hazard ratio [HR] 0.22; <i>p</i> < 0.0001) and median OS was not reached (HR: 0.31; <i>p</i> = 0.00015); pts who did not achieve MRD negativity were 4.5 times more likely to experience disease progression. Pts who became MRD negative at any time also had better outcomes with or without clinical complete response versus those who remained MRD positive (Figure). The probability of maintaining MRD negativity after induction was 2.3-fold greater for pts in the ABR arm (HR: 0.44; <i>p</i> = 0.022). Among all pts, those who maintained MRD negativity after 24 weeks had improved outcomes (median PFS 70.2 months) versus those who converted from MRD negative at 24 weeks to MRD positive during the maintenance period (median PFS 44.2 months; HR: 1.96; <i>p</i> < 0.0001).</p><p><b>Conclusions:</b> In the phase 3 ECHO trial, achieving MRD negativity was associated with improved PFS. MRD was a stronger prognostic factor for outcome than clinical response. Continuous therapy with acalabrutinib increased the probability of maintaining MRD negativity after induction, and sustained MRD negativity was associated with improved PFS, suggest","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_136","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300207","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":"GENOMIC AND TRANSCRIPTIONAL SINGLE-CELL HETEROGENEITY IN GERMINAL-CENTER LYMPHOMAS: INSIGHTS INTO FOLLICULAR LYMPHOMA TRANSFORMATION","authors":"S. Huerga-Domínguez, B. Ariceta, P. Aguirre-Ruiz, P. San Martín-Uriz, S. Sarvide, Á. López-Janeiro, D. Alignani, E. Muiños-Lopez, M. Abengozar-Muela, S. Browne, R. Figueroa, C. Grande, A. López-López, J. R. Rodríguez-Madoz, A. Vilas-Zornoza, S. Roa, F. Prósper, M. Canales","doi":"10.1002/hon.70094_179","DOIUrl":"https://doi.org/10.1002/hon.70094_179","url":null,"abstract":"<p>B. Ariceta equally contributing author.</p><p><b>Introduction:</b> The diversity of germinal centers has a significant role in the transformation of follicular lymphoma (FL). This heterogeneity in FL is driven by a combination of genetic and epigenetic modifications, and interactions with the tumor microenvironment (TME). Understanding how these mechanisms lead disease progression is crucial for identifying therapeutic targets and prognostic markers.</p><p><b>Methods:</b> We performed single-cell DNA sequencing (scDNA-seq) (Mission Bio Tapestri Platform), single-cell RNA sequencing (scRNA-seq), and spatial transcriptomics (10X Genomics) analysis on 5 lymph node samples at diagnosis: 3 DLBCL (1 GCB, 2 ABC) and 2 FL (1 transformed—tFL- and 1 non-transformed—ntFL-).</p><p><b>Results:</b> In the scRNA-seq analysis, malignant B cells clustered into 6 clusters. Light-zone (LZ) cells were specific to ntF, whereas tFL and GCB were enriched in dark zone/light zone (DZ/LZ) cells. Pre-memory B (pre-M) and pre-plasma cells predominated in ABC (Figure 1a). Differential expression analysis identified BCR activation (DZ-LZ), cytokine signaling (LZ), and pro-tumor pathways activation, including NF-kB (pre-M). Transcriptional similarities between tFL and GCB suggest a common precursor driven by BCR activation. However, GCB revealed a dominant cell-cycle dysregulation signature, while tFL showed an immune-evasion one.</p><p>T cell subclusters varied significantly across patients. ntFL was enriched in naïve CD4<sup>−</sup>CD8<sup>−</sup> and CD8<sup>+</sup> central memory T cells, while tFL and GCB were enriched in CD4<sup>+</sup> T cells. CD4<sup>+</sup> and CD8<sup>+</sup>Teff cells were predominant in ABC samples. CD4<sup>+</sup> T cells promoted T cell tolerance (IL6/STAT3, PD-1), while CD8<sup>+</sup>Teff cells exhibited high exhaustion marker expression. CD8<sup>+</sup>Teff cells from DLBCL and tFL showed stronger exhaustion profiles than ntFL. CD4<sup>+</sup> Tfh cells expressed genes involved in adhesion with malignant B cells, with significantly higher expression in DLBCL and tFL (Figure 1b).</p><p>In the scDNA-seq analysis, patients harbored mutations in chromatin-modifying genes (<i>KMT2D</i> and <i>EZH2</i>) and oncogenic genes (<i>NOTCH2</i>). In GCB and tFL samples, <i>KMT2D</i> variants were identified as early events, while <i>EZH2</i> (tFL) and <i>ATM</i> (GCB) mutations emerged as secondary events. A nonsense mutation in <i>TET2</i> was detected in non-B cells, suggesting the presence of clonal hematopoiesis (CH). A second scDNA-seq analysis was performed to investigate CH further, focusing on CH-related variants in 3 samples. All harbored 2 or 3 mutations in epigenetic modifier genes (<i>TET2</i>, <i>ASXL1,</i> and <i>DNMT3A</i>).</p><p>In the spatial transcriptomics analysis, 28,387 spots were examined. Deconvolution using paired scRNA-seq data confirmed an adequate representation of all cell types.</p><p><b>Conclusions:</b> These findings pr","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_179","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292040","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":"MECHANISMS OF RESISTANCE TO T-CELL REDIRECTING THERAPIES","authors":"A. A. Alizadeh","doi":"10.1002/hon.70093_68","DOIUrl":"https://doi.org/10.1002/hon.70093_68","url":null,"abstract":"<p>T-cell redirecting therapies, have revolutionized the management of diverse malignancies, especially B-cell non-Hodgkin lymphomas. Currently approved such therapies include T-cells that are engineered to express chimeric antigen receptors (CAR-T cells) and bispecific antibodies that bridge T-cells to diverse tumor antigens. Yet despite their remarkable efficacy and curative potential, resistance and relapse to these therapies remain significant hurdles, and unfortunately, still observed in most patients today. This presentation will explore the tumor-intrinsic mechanisms that contribute to such resistance in mature B-cell neoplasms, while also considering the roles of T-cell dysfunction and the tumor microenvironment (TME) in resistance phenotypes.</p><p>I will review data from several studies that have highlighted key mechanisms and pathways underlying such tumor intrinsic resistance. In one key study by Sworder et al. (<i>Cancer Cell</i>, 2023) a comprehensive simultaneous tumor and effector profiling (STEP) approach has been described to investigate resistance determinants in large B-cell lymphomas treated with anti-CD19 CAR T-cells. In addition to genetic and epigenetic mechanisms known to hamper target antigen expression of key tumor markers (such as CD19, CD20, CD22, and BCMA), these studies have revealed that genetic alterations in B cell identity genes like PAX5 and IRF8 may lead to lineage switch or loss of target antigens. Separately, these studies show how somatic gains driving upregulation of key immune checkpoints like PD-L1 upregulation can help tumors evade T-cell attacks. For bispecific antibodies, similar mechanisms, such as antigen loss, are also observed, suggesting shared challenges across therapies.</p><p>When considering non-tumor intrinsic mechanisms of resistance, the TME is also known to play a crucial role, with research indicating that immune-suppressed TME profiles correlate with poorer outcomes, likely by hindering T-cell function through axes such as PD-1, TIM-3, suppressive actions of Tregs, MDSCs, inhibitory cytokines, and others. T-cell exhaustion, driven by chronic antigen exposure and TME immunosuppression, is known to reduce effector functions and persistence, impacting both CAR-T and bispecific antibody efficacy. Conversely, TMEs with high B cell proliferation may predict better CAR-T responses, an unexpected feature that could also guide therapy selection.</p><p>I will highlight how such approaches to integrative genomic profiling, TME analysis, and T-cell functional assessments can enhance outcome prediction and personalize T-cell therapies. In addition to defining key gaps in our current knowledge, I will describe strategies to help bridge these gaps, toward optimizing existing therapies and developing next-generation interventions to overcome resistance, potentially improving long-term outcomes for patients with lymphomas and other tumors.</p><p><b>Keywords:</b> aggressive B-cell non-Hodgkin lymphoma</p","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_68","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292218","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":"GLOFITAMAB PLUS GEMCITABINE AND OXALIPLATIN (Glofit-GemOx) IN PATIENTS WITH RELAPSED/REFRACTORY (R/R) DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL): 2-YEAR FOLLOW-UP OF STARGLO","authors":"J. S. Abramson, M. Ku, M. Hertzberg, C. P. Fox, C. Herbaux, H. Huang, D. H. Yoon, W. S. Kim, H. Zhang, H. Abdulhaq, W. Townsend, E. Mulvihill, V. Orellana-Noia, R. Ta, H. Huang, M. J. Kallemeijn, A. Belousov, A. Bottos, L. Lundberg, G. P. Gregory","doi":"10.1002/hon.70093_76","DOIUrl":"https://doi.org/10.1002/hon.70093_76","url":null,"abstract":"<p><b>Introduction:</b> Glofitamab, a CD20:CD3 bispecific antibody, has shown durable responses as fixed duration monotherapy in R/R DLBCL after ≥ 2 prior lines of therapy (LOT; Dickinson et al. NEJM 2022). In the Phase 3 STARGLO trial, Glofit-GemOx demonstrated overall survival (OS) and progression-free survival (PFS) benefits over rituximab (R)-GemOx in autologous stem cell transplant (ASCT)-ineligible R/R DLBCL (Abramson et al. Lancet 2024). Here, we present updated efficacy and safety from the STARGLO trial (NCT04408638), including landmark analyses of patients (pts) in complete remission (CR).</p><p><b>Methods:</b> Pts were randomized 2:1 to receive Glofit-GemOx (8 cycles plus 4 cycles glofitamab monotherapy) or R-GemOx (8 cycles) and stratified by number of prior LOT (1 vs. ≥ 2) and refractoriness to their last therapy. After obinutuzumab pretreatment, glofitamab was given in Cycle (C) 1 as weekly step-up doses (2.5/10 mg) then 30 mg target dose every 21 days from C2 Day 1. Pts with only 1 prior LOT must have been ASCT-ineligible. Primary endpoint was OS. Secondary endpoints included independent review committee (IRC)-assessed PFS and CR rate. A landmark analysis of pts in CR at end of treatment (EOT) was performed.</p><p><b>Results:</b> Of 274 pts (Glofit-GemOx, <i>n</i> = 183; R-GemOx, <i>n</i> = 91), 172 (62.8%) had 1 prior LOT, 102 (37.2%) had ≥ 2 prior LOT, 153 (55.8%) were primary refractory, and 166 (60.6%) were refractory to their last therapy. Baseline characteristics were unchanged compared with the primary analysis and well balanced across arms.</p><p>With 2 years (yrs) of follow-up (data cut off: June 17, 2024; median follow-up: 24.7 months [mo]), Glofit-GemOx continued to confer superior OS (median: not evaluable [NE] vs. 13.5 mo; hazard ratio [HR] 0.60, 95% confidence interval [CI]: 0.42–0.85), median IRC-assessed PFS (13.8 vs. 3.6 mo; HR 0.41, 95% CI: 0.29–0.58), and CR rate (58.5 vs. 25.3%) versus R-GemOx. For Glofit-GemOx-treated pts in CR (<i>n</i> = 107), median duration of CR was not reached (95% CI: 27.2–NE; median CR follow-up, 18.2 mo [range: 15.2–19.3]). In pts with a CR at EOT (<i>n</i> = 82), the OS and PFS rates 1 yr after EOT were 89.3% and 82.4%, respectively.</p><p>The Glofit-GemOx safety profile was unchanged. Cytokine release syndrome (CRS) was the most common adverse event in glofitamab-exposed pts (Grade [Gr] 1, 32.0%; Gr 2, 10.5%; Gr 3, 2.3%). Events consistent with immune effector cell-associated neurotoxicity syndrome occurred in 4 pts (all concurrent with CRS; most Gr 1–2 [<i>n</i> = 3]). Exploratory biomarker and immune recovery data will be presented.</p><p><b>Conclusions:</b> With 2 yrs of follow-up, Glofit-GemOx sustained a clinically meaningful benefit in OS and PFS versus R-GemOx in ASCT-ineligible pts with R/R DLBCL, with most (82%) pts in CR at EOT still in remission. The safety profile was consistent with known risks of each drug. The updated analyses demonstrate durable remissions and maintain","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_76","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292221","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":"DURVALUMAB AND LENALIDOMIDE SHOWS SUPERIOR EFFICACY OVER SINGLE-AGENT DURVALUMAB IN REFRACTORY/ADVANCED CUTANEOUS T CELL LYMPHOMA: RESULTS FROM A RANDOMIZED PHASE 2 TRIAL","authors":"C. Querfeld, L. Chen, X. Wu, Z. Han, C. Su, Y. Yuan, M. Banez, J. Quach, T. Barnhizer, L. Crisan, S. T. Rosen, J. Zain","doi":"10.1002/hon.70094_399","DOIUrl":"https://doi.org/10.1002/hon.70094_399","url":null,"abstract":"<p><b>Introduction:</b> Advanced stages of cutaneous T cell lymphoma (CTCL) have an unfavorable prognosis. We have shown that CTCL escapes immune surveillance via immune checkpoint signaling such as the PD-1/PD-L1 axis. Selective targeting of the functionally exhausted malignant T cells in cutaneous T-cell lymphoma (CTCL) and distinct cells within the tumor microenvironment (TME) via PD1/PD-L1 blockade (durvalumab) may restore an anti-tumor immune response. We initiated the randomized Phase 2 portion to compare single agent durvalumab to durvalumab plus lenalidomide in relapsed/advanced CTCL (NCT03011814). The primary end point was objective response rate (ORR) using the global composite response (based on skin, blood, nodes, and viscera) according to consensus guidelines. Secondary end points included duration of response, progression-free survival, and toxicity. Relationships between gene expression profile, tumor-microenvironment (TME), and antitumor activity were exploratory end points.</p><p><b>Methods:</b> Adult patients with histologically confirmed MF or SS, who had failed ≥ 2 systemic therapies were enrolled and randomized 1:1 to single agent durvalumab (1500 mg (day 1 of 28-day cycle) or durvalumab (same dose) & lenalidomide (10 mg for cycle 1, 15 mg for cycle 2, then 20 mg for subsequent cycles daily for 21 days of each 28-day cycle). The study used a “pick a winner” design based on ORR. Serial skin and blood samples were collected to assess the impact on the TME and anti-tumor activity.</p><p><b>Results:</b> Among 25 patients [12 durvalumab; 13 durvalumab/lenalidomide; stage IB, 2 (17%) vs. 4 (31%); stage IIB, 5 (42%) vs. 3 (23%); stage III/IV, 5 (42%) vs. 6 (46%); large cell transformation 3 (25%) vs. 5 (38%)], the combination showed superior clinical activity, with an ORR of 75% versus 42% and a 12-month PFS of 73% (95% CI: 38%–91%) versus 36% (95% CI: 11%–63%) (Figure 1). Median PFS was 6.2 months for durvalumab and not reached for the combination. The most common treatment-emergent adverse events were more frequent in the durvalumab/lenalidomide arm versus durvalumab arm and included fatigue (<i>n</i> = 10), diarrhea (<i>n</i> = 6), anemia (5), decreased platelets (<i>n</i> = 5), leukopenia & neutropenia (<i>n</i> = 4), constipation (<i>n</i> = 4), and leg edema (<i>n</i> = 4). The majority of AEs with both treatment arms were mild to moderate in severity (grade I/II, 92%; grade III, 8 %). One grade IV neutropenia on combo arm was observed.</p><p><b>Conclusions:</b> This randomized phase 2 trial of durvalumab +/− lenalidomide evaluating anti-tumor activity demonstrated superior clinical activity of combinatorial durvalumab/lenalidomide versus single-agent durvalumab in refractory/advanced CTCL. Responses were durable and ongoing, and treatment was well tolerated. Our correlative results from sequential skin biopsies demonstrated immune signatures for enhanced anti-tumor responses that may be predictive of response to check","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_399","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292473","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":"FINAL SAFETY ANALYSIS IN PARTICIPANTS WITH HEMATOLOGIC MALIGNANCIES WHO RECEIVED ALLOGENEIC STEM CELL TRANSPLANT AFTER PEMBROLIZUMAB THERAPY","authors":"J. Kuruvilla, P. Armand, A. F. Herrera, V. Ribrag, C. Thieblemont, B. von Tresckow, S. Thompson, K. E. Ryland, R. Z. Yusuf, P. L. Zinzani","doi":"10.1002/hon.70094_351","DOIUrl":"https://doi.org/10.1002/hon.70094_351","url":null,"abstract":"<p><b>Introduction:</b> Allogeneic stem cell transplant (allo-SCT) carries a relevant risk of transplantation-related mortality (TRM), especially from graft-versus-host disease (GVHD), particularly in patients previously treated with checkpoint inhibitors. Final safety results in participants (pts) with hematologic malignancies who received allo-SCT after pembrolizumab (pembro) therapy across a variety of pembro clinical studies are presented.</p><p><b>Methods:</b> Data were pooled from 10 phase 1–3 studies (KEYNOTE-A33 [NCT04317066], KEYNOTE-013 [NCT01953692], KEYNOTE-155 [NCT02684617], KEYNOTE-051 [NCT02332668], KEYNOTE-B68 [NCT04875195], KEYNOTE-087 [NCT02453594], KEYNOTE-170 [NCT02576990], KEYNOTE-183 [NCT02576977], KEYNOTE-204 [NCT02684292], and MK4280-003 [NCT03598608]). Outcomes of interest included acute and chronic GVHD, incidence of allo-SCT–related adverse events, overall survival (OS), and TRM.</p><p><b>Results:</b> A total of 112 pts were reported to have received allo-SCT, 14 were not included in the analysis (13 received allo-SCT > 2 years after last dose of pembro and 1 had a missing date of allo-SCT). Median duration on study treatment was 5.6 months (range, 0.03–29.7), and median time from last dose of pembro to first allo-SCT was 4.9 months (range, 1–20). Of 98 evaluable pts, 67 pts (68%) received intervening therapy between pembro and allo-SCT. At time of transplant, 47 pts (48%) had active disease, 39 pts (40%) were in remission, and 12 (12%) had unknown disease status. A total of 91 pts (93%) received allo-SCT only; 7 (7%) received autologous SCT followed by allo-SCT. Among 63 pts (64%) who developed GVHD, 52 (53%) experienced acute events (Glucksberg II-IV [<i>n</i> = 34] and Glucksberg III-IV [<i>n</i> = 19]) and 24 (25%) experienced chronic events (mild [<i>n</i> = 11], moderate [<i>n</i> = 8], and severe [<i>n</i> = 5]). The most common sites for chronic GVHD were skin (<i>n</i> = 15), oral mucosa (<i>n</i> = 12), and liver (<i>n</i> = 9). Other predetermined non-GVHD events of clinical interest occurred in 42 pts (43%), categorized as critical illness (30%), febrile syndrome treated with corticosteroids (1%), immune-mediated adverse events (10%), pulmonary complications (14%), and venoocclusive liver disease (3%). The most common predetermined events of clinical interest (≥ 5%) were febrile neutropenia and pneumonia (6% each). The most common of the other adverse events not included in the 5 categories above (≥ 2%) were grade ≤ 2 pyrexia (5%) and rash (2%). Median OS was not reached (NR; 95% CI: NR-NR) post–allo-SCT, with 100-day, 24-month, and 48-month OS rates of 94%, 70%, and 68%, respectively. Estimated TRM rates at 100 days, 24 months, and 48 months were 5%, 21%, and 21%, respectively.</p><p><b>Conclusion:</b> The inclusion of additional pts in this analysis revealed comparable rates of acute and chronic GVHD, OS, and TRM compared to previous studies and historical benchmarks, thus, reinforcing the role of allo-","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_351","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292664","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":"CD19 CAR-T CELL THERAPY IN RELAPSED/REFRACTORY SOLID ORGAN TRANSPLANT-RELATED LYMPHOPROLIFERATION: A LYSA ANALYSIS OF THE FRENCH COHORT DESCAR-T","authors":"E. Corvilain, R. Di blasi, C. Thieblemont, M. Cheminant, B. Guffroy, J. Decroocq, A. Campidelli, M. Rubio, F. Claves, S. Carras, M. Mothy, V. Dupont, R. Houot, S. Choquet","doi":"10.1002/hon.70094_381","DOIUrl":"https://doi.org/10.1002/hon.70094_381","url":null,"abstract":"<p><b>Introduction:</b> Post-transplant lymphoproliferative disorder (PTLD) is a rare but severe complication of solid organ transplantation (SOT). First-line treatment typically involves reducing immunosuppressive drugs (ID) alongside Rituximab, followed by maintenance for partial responders (PR) or immunochemotherapy for progression disease (PD). The management of refractory/relapsed (R/R) remains uncertain. The role of CD19 CAR-T cells is not established, though case reports and a series of 22 patients have been published.</p><p><b>Methods:</b> We conducted a retrospective analysis of the multicenter French DESCAR-T registry (NCT04328298) to identify patients treated by CD19 CAR-T cells for SOT-related PTLD. The study period spanned from July 2019 to September 2024. Survival analyses were performed using Kaplan-Meier models.</p><p><b>Results:</b> We identified 12 patients (5 males) treated by CD19 CAR-T cells. Prior SOTs included kidneys (<i>n =</i> 10), liver (<i>n =</i> 1) and lungs (<i>n =</i> 1). In all but one patient, lymphoproliferation occurred more than one year after SOT. All PTLD were classified as diffuse large B cell lymphoma (EBV-associated in 10/11, 1 not available (NA)), except one diagnosed as transformed marginal zone lymphoma. CAR-T cells were administered as second line treatment in 3 patients, and beyond second line in 9 patients. The median age at infusion was 41 years (IQR: 22–62). At diagnosis, performance status was 0-1 in 11/12, Ann-Arbor stage was III-IV in 8/12 and aaIPI score was 1-2 in 11/12 patients. The median lymphocyte rate at apheresis was 0.6G/L (IQR:0-3.4). CAR-T products used included axicabtagene ciloleucel (<i>n =</i> 9) and tisagenlecleucel (<i>n =</i> 3). Ten patients received cyclophosphamide-fludarabine as conditioning regimen (2 NA). ID was modified in all patients at diagnosis then before apheresis. At CAR-T infusion, patients were receiving corticosteroids alone (<i>n</i> = 8), m-TOR inhibitor (<i>n</i> = 1), corticosteroids and calcineurin inhibitor (<i>n =</i> 1), or no ID (<i>n =</i> 2). Cytokine-release-syndrome occurred in all patients with grade 3–4 in 2 cases. Immune-effector-cell associated neurotoxicity (ICANS) was observed in 7 patients with grade 3–4 in 2 cases. Hypogammaglobulinemia (< 5 g/L) was reported in 70% of patients (7/10) without need of immunoglobulins replacement. The best ORR was 82%, including 64% complete response, 18% PR and 18% PD. With a median follow-up of 12.9 months (mo) (95% CI: 4.5-(-)), median progression-free-survival and overall survival were both 16.6 mo (95% CI: 1.1-(-) and 2-(-), respectively) (Figure). Six patients died among which three due to PD and 2 from high grade ICANS (one acute, one late) (1 NA). Among the six surviving patients, one experienced kidney rejection requiring a return to dialysis.</p><p><b>Conclusion:</b> This is the second reported series of patients with R/R SOT-related PTLD treated with CD19 CAR-T cells. Our findings suggest that ","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_381","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292685","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":"IMAGING PITFALLS IN PEDIATRIC, ADOLESCENT, AND YOUNG ADULT HODGKIN LYMPHOMA: A SEARCH FOR CAYAHL INITIATIVE TO BRIDGE MULTIDISCIPLINARY PATIENT CARE","authors":"N. Dakhallah,&nbsp;J. Steglich,&nbsp;A. L. Alazraki,&nbsp;S. M. Castellino,&nbsp;K. Dieckmann,&nbsp;J. E. Flerlage,&nbsp;C. Gowdy,&nbsp;M. B. Heneghan,&nbsp;K. M. Kelly,&nbsp;H. A. Lai,&nbsp;C. Mauz-Körholz,&nbsp;K. M. McCarten,&nbsp;S. Milgrom,&nbsp;R. Pabari,&nbsp;M. Palese,&nbsp;S. D. Voss,&nbsp;L. Kurch,&nbsp;D. Stoevesandt,&nbsp;J. Seelisch","doi":"10.1002/hon.70094_374","DOIUrl":"https://doi.org/10.1002/hon.70094_374","url":null,"abstract":"<p>N. Dakhallah and J. Steglich equally contributing author.</p><p><b>Introduction:</b> Hodgkin lymphoma (HL) is a highly curable malignancy in children, adolescents, and young adults (CAYA), and current treatment strategies aim to minimize adverse late effects. Many patients are enrolled in clinical trials that include centralized review for both initial and interim staging. While academic guidelines provide a structured framework, real-world clinical scenarios sometimes present imaging pitfalls that require nuanced judgment.</p><p><b>Methods</b>: The Staging, Evaluation and Response Criteria (SEARCH) for CAYAHL initiative was established in 2011 to harmonize staging and response criteria in HL in CAYA. However, applying these published criteria can present challenges in situations where imaging pitfalls are encountered. This SEARCH for CAYAHL project is a transatlantic collaboration among experts in diagnostic radiology, nuclear medicine radiology, radiation oncology and pediatric oncology. A working group first identified the most frequent and relevant imaging pitfalls in HL. Through literature review, imaging and clinical experience, and the use of specific real-word cases, this effort defines and describes imaging pitfalls in HL in CAYA.</p><p><b>Results</b>: Morphologic and metabolic imaging pitfalls in HL refer to the misinterpretation of findings that can occur during staging, disease evaluation, or post-treatment surveillance. These radiological findings are not indicative of disease but are rather manifestations of other causes that are specific to each tissue or organ. In this work, we explore pitfalls resulting from suboptimal imaging conditions, concurrent inflammatory, infectious, or other causes. We discuss organ specific pitfalls involving the lymph nodes, lungs, bone, bone marrow, spleen, liver and Waldeyer’s ring and present important considerations on imaging following the completion of therapy.</p><p><b>Conclusions</b>: This collaborative effort aims to disseminate insights gained from decades of centralized review experience in North American and European trials to optimize patient care by integrating imaging and clinical expertise. Although not intended as a comprehensive staging guide, it highlights recurrent imaging pitfalls that may lead to diagnostic uncertainty. By encouraging interdisciplinary exchange, this work seeks to complement existing literature and serve as a troubleshooting guide for situations where clinical realities diverge from academic paradigms, ultimately paving the way for improved patient outcomes.</p><p><b>Keywords:</b> Hodgkin lymphoma (pediatric, adolescent, and young adult)</p><p><b>Potential sources of conflict of interest:</b></p><p><b>C. Mauz-Körholz</b></p><p><b>Employment or leadership position:</b> Institutional research grant Merck</p><p><b>Consultant or advisory role:</b> Merck advisory board</p>","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_374","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292688","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":"MULTICENTER REAL-WORLD OUTCOMES OF FRONTLINE POLA-R-CHP IN TREATMENT NAÏVE DLBCL","authors":"S. K. Thiruvengadam,&nbsp;L. Chen,&nbsp;S. Buller,&nbsp;V. Iyengar,&nbsp;G. Pelaez,&nbsp;V. Pizzuti,&nbsp;A. Major,&nbsp;Y. Youssef,&nbsp;Y. Sawalha,&nbsp;D. Wallace,&nbsp;M. Masterson,&nbsp;N. Birrer,&nbsp;A. Bock,&nbsp;A. Nedved,&nbsp;Y. Wang,&nbsp;T. Lucido,&nbsp;J. Rhodes,&nbsp;J. Crombie,&nbsp;D. Montana,&nbsp;M. Stanchina,&nbsp;J. P. Alderuccio,&nbsp;A. Gibson,&nbsp;P. A. Riedell,&nbsp;T. Jain,&nbsp;B. Heyman,&nbsp;H. Rasmussen,&nbsp;C. Ujjani,&nbsp;P. Gould,&nbsp;H. Cherng,&nbsp;A. Bahnasy,&nbsp;T. Hilal,&nbsp;B. Parker,&nbsp;M. A. Moustafa,&nbsp;S. Pak,&nbsp;M. Okwali,&nbsp;J. Chicola,&nbsp;J. M. Manzano,&nbsp;C. Goth,&nbsp;D. Russler-Germain,&nbsp;P. Torka,&nbsp;A. F. Herrera","doi":"10.1002/hon.70094_289","DOIUrl":"https://doi.org/10.1002/hon.70094_289","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Introduction:&lt;/b&gt; Incorporation of polatuzumab vedotin into initial therapy of diffuse large B-cell lymphoma (DLBCL) became a standard of care (SOC) based on the POLARIX trial, which demonstrated improvement in progression free survival (PFS) with pola-R-CHP compared to R-CHOP. In this study we evaluate the safety and efficacy of SOC frontline pola-R-CHP for treatment naïve DLBCL.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; We performed a multicenter retrospective study including patients (pts) from 17 US centers. Pts with treatment naïve DLBCL who received pola-R-CHP as frontline therapy outside of the setting of a clinical trial were eligible. The primary objective was to evaluate the PFS of SOC pola-R-CHP in frontline DLBCL. Secondary objectives included evaluating the safety of the regimen as well as secondary measures of efficacy such as overall response rate (ORR), complete response rate (CRR), overall survival (OS), and time to next treatment (TTNT).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; A total of 535 pts treated with pola-R-CHP between August 2021 to September 2024 were included. At least one cycle of alternate treatment was given in 28% pts before switching to pola-R-CHP (78% of these pts received R-CHOP). The median age was 67 years (range 22–90), 41% were female, 17% had ECOG ≥ 2, 89% had advanced stage, 45% had &gt; 1 extranodal site, 63% had elevated LDH, 63% had an IPI of 3–5, 33% had bulky disease (≥ 7.5 cm), 3.3% had central nervous system involvement, 29% were double expressor, 3.9% were double/triple hit, 34% had germinal center B-cell subtype (GCB) and 59% had non-GCB subtype by Hans.&lt;/p&gt;&lt;p&gt;ORR was 92% with a CRR of 80% in all pts; ORR was 93% versus 92% (CRR 77% vs. 81%) for GCB versus non-GCB. At a median follow up of 11 months (range 0.5–32), 1-year PFS was 81% (95% CI: 77%–84%) among all pts, 78% for GCB versus 82% for non-GCB; 1-year OS was 91% (95% CI: 87%–93%) among all pts and 91% for both cell of origin (COO) subgroups. Subsequent treatment was given in 16% pts with median TTNT 5.8 months (range 0.8–18).&lt;/p&gt;&lt;p&gt;With respect to safety, 37% developed any grade neuropathy with 1.1% grade ≥ 3, 20% had grade ≥ 3 infection, 3.4% had cardiomyopathy, 31% had grade ≥ 3 neutropenia, 15% had grade ≥ 3 febrile neutropenia, and 15% had grade ≥ 3 thrombocytopenia. 31% were hospitalized and 6.0% had ICU admission for treatment-related adverse events. Treatment was discontinued in 13% due to toxicity (4.5%), progression (3.6%), or other reasons (4.7%). Seven deaths (1.3%) were deemed to be related to pola-R-CHP.&lt;/p&gt;&lt;p&gt;In univariate Cox models, &gt; 1 extranodal sites, bulky disease, CNS involvement, and double/triple hit were associated with inferior PFS (&lt;i&gt;p&lt;/i&gt; &lt; 0.05) and ECOG ≥ 2, elevated LDH, and IPI 3–5 were associated with inferior OS and PFS (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). COO was not significantly associated with PFS or OS.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusion:&lt;/b&gt; The results of our study suggest that SOC pola-R-CHP is safe and effective for treatment naïve DLBCL, with outcomes","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_289","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292724","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}