Hematological Oncology最新文献

{"title":"FOLLICULAR LYMPHOMA TRANSFORMATION: REAL-WORLD ANALYSIS INCLUDING EFFECT OF RITUXIMAB/OBINUTUZUMAB","authors":"D. Shpitzer, C. Perry, I. Avivi","doi":"10.1002/hon.70094_226","DOIUrl":"https://doi.org/10.1002/hon.70094_226","url":null,"abstract":"<p><b>Background</b>: Follicular lymphoma (FL) carries a 2–3% annual risk of transformation to aggressive lymphoma. While most studies focus on transformed FL (T-FL) in previously treated patients (pts), limited data exist on transformation without prior therapy. Additionally, the impact of Obinutuzumab (O) versus Rituximab (R) on T-FL risk is not well documented.</p><p><b>Aims</b>: To provide real-world data (RWD) on FL pts with and without prior anti-FL therapy exposure who developed T-FL, investigating risk factors, treatment patterns, and outcomes.</p><p><b>Methods</b>: We retrospectively reviewed electronic medical records of 1145 FL pts, diagnosed between 2010–2023, age ≥ 18 years, and recorded within Maccabi Healthcare Services. T-FL was defined as a subsequent diagnosis of diffuse large B-cell lymphoma (DLCL) without prior DLCL history. We analyzed transformation risk factors, impact of comorbidities, treatment regimens, and overall survival (OS).</p><p><b>Results</b>: Of 1145 FL pts, 9% (<i>n</i> = 104) developed T-FL over a median follow-up of 71 months (m), reflecting a 1.43% annual transformation rate. Median time to transformation was 42 m. No significant differences were found in age (63 vs. 61 years, <i>p</i> = 0.1) or gender (males 48% vs. 47%, <i>p</i> = 0.8) between T-FL and non-T-FL pts. Charlson Comorbidity Index (CCI) was higher in T-FL pts (median 4 vs. 3, <i>p</i> = 0.005).</p><p>Among 103 T-FL cases, 47% (<i>n</i> = 49) were treatment-naïve, and 53% (<i>n</i> = 54) had prior therapy (26 at diagnosis, 28 after watch-and-wait or local radiotherapy). Median treatment lines among treated pts was 1 (range 1–3). First-line regimens included R-CHOP/CVP (33%, <i>n</i> = 213, predominantly CHOP), R-bendamustine (B) (28%, <i>n</i> = 181), R-monotherapy (11%, <i>n</i> = 71), OB (20%, <i>n</i> = 133), and O-CHOP/CVP (9%, <i>n</i> = 57).</p><p>Median time from initiation of first-line therapy to T-FL in previously treated pts was 23 m, with no significant difference between those treated at diagnosis and those initially managed with watch-and-wait (24 vs. 21 m, <i>p</i> = 0.08). Multivariate analysis revealed that O- vs. R-based regimens (HR 0.43, <i>p</i> = 0.025) and maintenance therapy (HR 0.41, <i>p</i> < 0.001) were associated with reduced transformation risk, whereas B-containing regimens were linked to an increased risk of T-FL (HR 1.52, <i>p</i> = 0.017).</p><p>Median OS from FL diagnosis was shorter in T-FL pts (154 m vs. not reached, <i>p</i> < 0.001), with a median OS since T-FL of 125 m. Previously treated T-FL pts had shorter OS than treatment-naïve pts (34.6 m vs. not reached, <i>p</i> = 0.001). Prior anti-FL therapy (HR 2.23, <i>p</i> < 0.001), male gender (HR 1.77, <i>p</i> = 0.006), and older age at transformation (HR 1.03, <i>p</i> = 0.02) were linked to shorter OS.</p><p><b>Conclusions</b>: Our RWD on T-FL demonstrates several key findings: O-based regimens significantly reduce transformation risk in FL; B-c","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_226","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299963","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":"POLATUZUMAB VEDOTIN, RITUXIMAB, GEMCITABINE AND OXALIPLATIN (POLA-R-GEMOX) FOR RELAPSED/REFRACTORY (R/R) DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL): PHASE III POLARGO TRIAL","authors":"J. Sancho, Z. Li, T. P. Vassilakopoulos, A. Viardot, A. McMillan, M. Sinan Dal, J. Pereira, J. S. Kim, L. Qiu, C. L. Batlevi, R. Ibrahim, J. Hernandez, B. McCall, Y. Jiang, M. Yan, W. Harris, L. Musick, C. Haioun, M. Matasar","doi":"10.1002/hon.70093_7","DOIUrl":"https://doi.org/10.1002/hon.70093_7","url":null,"abstract":"<p><b>Introduction:</b> Polatuzumab vedotin is approved in frontline and R/R DLBCL; the latter involving combination with bendamustine and rituximab (Tilly et al. 2022; Sehn et al. 2019). Alternative treatments are needed for patients (pts) with R/R DLBCL. We present efficacy and safety results from the randomized cohort of the POLARGO trial (NCT04182204) evaluating Pola-R-GemOx versus R-GemOx in pts with R/R DLBCL after ≥ 1 prior therapy.</p><p><b>Methods:</b> Following a Pola-R-GemOx safety run-in (<i>n</i> = 15), pts with R/R DLBCL (not otherwise specified [NOS] or transformed indolent lymphoma) ineligible for autologous stem cell transplant were randomized 1:1 to receive polatuzumab vedotin (1.8 mg/kg) plus R-GemOx (R, 375 mg/m<sup>2</sup>; Gem, 1000 mg/m<sup>2</sup>; Ox, 100 mg/m<sup>2</sup>) or R-GemOx alone every 21 days for ≤ 8 cycles. Primary endpoint was overall survival (OS). Secondary endpoints included investigator-assessed progression-free survival (PFS), and independent review committee-assessed objective response rate (ORR) and complete response rate (CRR) at end of treatment (EOT) by PET-CT.</p><p><b>Results:</b> In total, 270 pts with DLBCL were enrolled (median age 66 [range 20–89] years), including 176 (65.2%) pts after 1 prior therapy. Of 246 pts with DLBCL NOS, 143 (58.1%) had primary refractory disease. As of Nov 29, 2024, in the randomized cohort (<i>N</i> = 255; median OS follow-up 24.6 months), a statistically significant OS benefit was observed with Pola-R-GemOx (<i>n</i> = 129) versus R-GemOx (<i>n</i> = 126; hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.43–0.83; <i>p</i> = 0.0017; Figure). Median OS was 19.5 months (95% CI: 13.3–not evaluable) for Pola-R-GemOx versus 12.5 months (95% CI: 8.9–15.8) for R-GemOx. OS benefit was consistent across most subgroups, including ABC (HR 0.53, 95% CI: 0.3–0.9) and GCB (HR 0.54, 95% CI: 0.3–0.9) subtypes by gene expression profiling. Key secondary endpoints are shown in the Table. In the safety-evaluable pts (Pola-R-GemOx, <i>n</i> = 128; R-GemOx, <i>n</i> = 125), median number of cycles received was higher with Pola-R-GemOx versus R-GemOx (7.5 versus 4.0) and Grade (Gr) 3–4 adverse event (AE) rates were similar (57.0% versus 58.4%), with higher rates of thrombocytopenia (34.4% versus 26.4%) and infections (14.1% versus 8.0%) with Pola-R-GemOx. Peripheral neuropathy (PN) was more common with Pola-R-GemOx versus R-GemOx (57.0% versus 28.8%); primarily Gr 1 (37.5% versus 23.2%). Five pts had Gr 3 PN in the Pola-R-GemOx arm. Treatment discontinuation rates due to AEs were higher with Pola-R-GemOx (23.4%) versus R-GemOx (8.0%). Gr 5 AEs were higher with Pola-R-GemOx versus R-GemOx (11.7% versus 4.0%), primarily driven by infections including COVID-19.</p><p><b>Conclusion:</b> Pola-R-GemOx demonstrated a statistically significant and clinically meaningful benefit in OS and PFS, with a 40% reduction in risk of death relative to R-GemOx. Pola-R-GemOx is an alternative treatment ","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_7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300090","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":"THE ROLE OF ARTIFICIAL INTELLIGENCE IN PATHOLOGIC DIAGNOSIS","authors":"P. Brousset","doi":"10.1002/hon.70093_8","DOIUrl":"https://doi.org/10.1002/hon.70093_8","url":null,"abstract":"<p>Over the last ten years, there have been thousands of papers describing the potential role of artificial intelligence (AI) algorithms in medical decision making. The impact of AI breakthroughs seems to be major in the field of medical image analysis in which such algos are supposed to do a better job than medical doctors, especially in radiology. Although the use of AI in medicine will increase over time, today the use of AI algos in medical decision assistance is quite limited. Radiology images are directly obtained from a machine whereas histopathology images are converted (digitized) from colored tissue sections on glass slides. The latter represent a tremendous source of heterogeneity explained by inter laboratory variations of tissue section processing. So far, most of the algos proposing automatic analysis of histopathology images are based on convolutional neural networks (CNN) which are extremely sensitive to variations of image heterogeneity and thus prone to overfitting. In other words, an algo trained on pictures produced in lab A is unable to recognize the same pictures obtained from lab B. In this presentation, different alternatives to circumvent CNN (deep learning) limitations will be presented. One of the strategy is to use large scale AI models so called foundation models (FM) based on transformer architectures which are trained on huge amounts of pictures. Another approach, less costly in terms of data input for training, is to use cartesian genetic programming (CGP) algos which, in addition, fill the gap of explainability of decision making. The final goal is to come out with AI solutions proposing a robust (accurate) assistance in picture analysis that can be run in every pathology laboratory regardless of tissue processing variations.</p><p><b>Keywords:</b> bioinformatics; computational and systems biology; pathology and classification of lymphomas</p><p>No potential sources of conflict of interest.</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_8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300092","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":"THE ROLE OF ARTIFICIAL INTELLIGENCE IN IMAGING READINGS","authors":"I. Buvat","doi":"10.1002/hon.70093_9","DOIUrl":"https://doi.org/10.1002/hon.70093_9","url":null,"abstract":"<p>Artificial intelligence (AI) is gaining ground in medical imaging thanks to the increasing availability of open datasets and shared deep learning models. In the context of imaging readings, it can mainly serve two purposes. The first is to automate the detection of abnormalities and the extraction of quantitative features from the images. The second is to predict the future of the patient based on image content possibly supplemented by clinical, pathological and/or biological information.</p><p>In this talk, we will show that AI can already be used to automate a number of tedious tasks often prone to intra- and inter-reader variability, such as lesion detection and segmentation from whole-body [18F]-FDG PET/CT images. This enables automated calculation of prognostic biomarkers from these images, such as the total metabolically active tumor volume, and exploration of the prognostic or predictive values of numerous candidate radiomic biomarkers. We will also discuss the variability between different AI algorithms, requiring the establishment of benchmarks to determine the performance of each AI algorithm and its compliance with interpretation rules agreed by medical experts.</p><p>In a second part, we will present the challenging task of predicting treatment response or patient outcome based on image readings. We'll explain how AI can help make the most of image content. The differences between using end-to-end deep learning and using radiomic features associated with machine learning will be explained, highlighting the advantages and limitations of each approach for prediction tasks. In addition to medical images, the inclusion of non-imaging data in prognostic and predictive models may be necessary to improve performance. We will illustrate how this can be achieved. The challenges associated with using AI for inference will be described based on examples from the literature and our own experience.</p><p><b>Keywords:</b> diagnostic and prognostic biomarkers; PET-CT; risk models</p><p>No potential sources of conflict of interest.</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_9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300093","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":"CONFERENCE SCHEDULE (updated on 15 May 2025)","authors":"","doi":"10.1002/hon.70092","DOIUrl":"https://doi.org/10.1002/hon.70092","url":null,"abstract":"<p>\u0000 \u0000 </p><p>\u0000 \u0000 </p><p>\u0000 \u0000 </p><p>\u0000 \u0000 </p><p>\u0000 \u0000 </p><p>\u0000 \u0000 </p><p>\u0000 \u0000 </p><p>\u0000 \u0000 </p><p>\u0000 \u0000 </p><p>\u0000 \u0000 </p><p>\u0000 \u0000 </p><p>\u0000 \u0000 </p><p>\u0000 \u0000 </p><p>\u0000 \u0000 </p><p>\u0000 \u0000 </p><p>\u0000 \u0000 </p><p>\u0000 \u0000 </p><p>\u0000 \u0000 </p><p>\u0000 \u0000 </p><p>\u0000 \u0000 </p><p>\u0000 \u0000 </p><p>\u0000 \u0000 </p><p>\u0000 \u0000 </p><p>\u0000 \u0000 </p><p>\u0000 \u0000 </p><p>\u0000 \u0000 </p><p>\u0000 \u0000 </p><p>\u0000 \u0000 </p><p>\u0000 \u0000 </p><p>\u0000 \u0000 </p><p>\u0000 \u0000 </p><p>\u0000 \u0000 </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.70092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299592","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":"ULTRA-LOW DOSE RADIOTHERAPY (ULDR) (4Gy) FOR INDOLENT ORBITAL ADNEXAL LYMPHOMAS (IOAL): AN INTERNATIONAL LYMPHOMA RADIATION ONCOLOGY GROUP STUDY","authors":"L. Shen,&nbsp;B. S. Imber,&nbsp;C. C. Pinnix,&nbsp;J. Yahalom,&nbsp;A. Cajo,&nbsp;J. R. Gunther,&nbsp;T. Lin,&nbsp;M. P. MacManus,&nbsp;M. Bressel,&nbsp;M. Levis,&nbsp;U. Ricardi,&nbsp;C. L. Holloway,&nbsp;A. K. Ng,&nbsp;L. S. Constine,&nbsp;T. C. Igwe,&nbsp;D. Huang,&nbsp;D. C. Hodgson,&nbsp;Y. Y. Sum,&nbsp;J. P. Plastaras,&nbsp;J. A. Baron,&nbsp;M. Harris,&nbsp;T. Illidge,&nbsp;S. Taguchi,&nbsp;M. Oguchi,&nbsp;J. L. Brady,&nbsp;N. G. Mikhaeel,&nbsp;Y. D. Tseng,&nbsp;S. Davis,&nbsp;K. Elsayad,&nbsp;H. Eich,&nbsp;M. S. Binkley,&nbsp;A. Hashmi,&nbsp;L. K. Ballas,&nbsp;K. W. Yeoh,&nbsp;I. H. Sin,&nbsp;A. Wirth","doi":"10.1002/hon.70093_109","DOIUrl":"https://doi.org/10.1002/hon.70093_109","url":null,"abstract":"<p><b>Introduction:</b> ULDR is reported to be effective for a range of indolent lymphomas. This is particularly relevant for lymphomas of the orbit where standard radiotherapy doses may be associated with long term sequelae. This large, international retrospective study evaluates the efficacy of 4Gy radiotherapy including outcomes in patient subsets and late toxicity.</p><p><b>Methods:</b> Eligible patients received 4Gy radiotherapy for IOAL at 18 centres between 2006 and 2024. Of 320 patients entered, a preliminary analysis was performed for 270 patients (321 orbits) with complete data available. Freedom from local failure (FFLF) was measured from commencement of radiotherapy (or from date of first response assessment for the landmark analysis). The study met local institutional review board requirements.</p><p><b>Results:</b> The median age at diagnosis of IOAL was 68 years (range 22–97), with 58% females. Histology was marginal zone lymphoma in 66% of orbits and location was conjunctival (solely) in 23%. Radiotherapy was given to the whole orbit in 72% of orbits, conjunctiva only in 19% and other partial orbit volumes in 9%. The median followup was 2.4 years (inter-quartile range 1–4.3). Initial complete and partial response rates (per orbit) were 64% (95% CI: 58–69) and 34% (95% CI: 29–40) respectively, at a median of 72 days following RT. Five-year FFLF was 86% (95% CI: 80–90) for all treated orbits. In a landmark analysis five-year FFLF was 90% (95% CI: 83–95) after an initial CR to radiotherapy, and 83% (95% CI: 73–89) after an initial PR (Figure). Five-year FFLP were 89% (95% CI: 83–93) and 78% (95% CI: 65–87) for marginal zone lymphoma (MZL) and other histologies, respectively; and 86% (95% CI: 80–91) and 84% (95% CI: 71–91) for conjunctiva-only and other subsites, respectively. Symptoms were reported prior to radiotherapy in 91% of orbits. Complete and partial symptom resolution were reported in 70% and 25% of orbits, respectively. Late effects were uncommon and mild, including dry eye in 16% (all grade 1), cataract in 5%, retinopathy in 1% and glaucoma in &lt; 1%.</p><p><b>Conclusion:</b> In a large, multicentre experience of ULDR for IOAL, durable local control and symptom relief were achieved for the large majority of treated orbits, and with no reported long-term sequelae in 80%. This preliminary analysis also suggests numerically superior outcomes for orbits achieving initial CR and for MZL histology. A final analysis of all enrolled patients is pending.</p><p><b>Keywords:</b> radiation therapy; extranodal non-Hodgkin lymphoma; indolent non-Hodgkin lymphoma</p><p><b>No potential sources of conflict of interest.</b></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_109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299593","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":"LISOCABTAGENE MARALEUCEL (LISO-CEL) IN PATIENTS (PTS) WITH RELAPSED OR REFRACTORY (R/R) MARGINAL ZONE LYMPHOMA (MZL) IN THE PHASE 2 TRANSCEND FL STUDY","authors":"M. L. Palomba,&nbsp;S. J. Schuster,&nbsp;R. Karmali,&nbsp;A. P. Skarbnik,&nbsp;J. S. Abramson,&nbsp;K. Ardeshna,&nbsp;P. Borchmann,&nbsp;B. T. Hill,&nbsp;A. M. Garcia-Sancho,&nbsp;A. Pinto,&nbsp;A. P. Rapoport,&nbsp;G. Cartron,&nbsp;I. Fleury,&nbsp;K. Izutsu,&nbsp;M. Kamdar,&nbsp;S. Mielke,&nbsp;A. M. Barbui,&nbsp;J. L. Reguera Ortega,&nbsp;L. J. Nastoupil,&nbsp;S. Ahmed,&nbsp;M. Bar,&nbsp;L. Diaz,&nbsp;V. Diab,&nbsp;M. Vedal,&nbsp;S. Colicino,&nbsp;A. Avilion,&nbsp;R. Nishii,&nbsp;F. Morschhauser","doi":"10.1002/hon.70093_55","DOIUrl":"https://doi.org/10.1002/hon.70093_55","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Introduction:&lt;/b&gt; There remains an unmet need for effective and safe treatment options for pts with R/R MZL. TRANSCEND FL (NCT04245839) is a global, phase 2, single-arm, multicohort study that evaluates the efficacy and safety of the anti-CD19 CAR T cell therapy, liso-cel, in pts with R/R FL or MZL. Here, we present the primary analysis in pts with R/R (third-line or later) MZL.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; Pts with R/R MZL who received ≥ 2 prior lines of systemic therapy, including a combination of an anti-CD20 antibody and an alkylating agent, or had relapsed disease after HSCT were eligible. Pts received liso-cel (100 × 10&lt;sup&gt;6&lt;/sup&gt; CAR&lt;sup&gt;+&lt;/sup&gt; T cells) after lymphodepleting chemotherapy (LDC). Bridging therapy was allowed, but reconfirmation of measurable disease was needed before LDC. The primary endpoint of ORR per independent review committee by CT using Lugano 2014 criteria (null hypothesis [H&lt;sub&gt;0&lt;/sub&gt;]: ≤ 50%) and key secondary endpoint of CR rate (H&lt;sub&gt;0&lt;/sub&gt;: ≤ 5%) were tested hierarchically.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; At data cutoff, 77 pts were leukapheresed, 67 (87%) received liso-cel (safety set), and 66 (86%) were efficacy evaluable. Median (range) age was 62 y (37–81), 85% had Ann Arbor stage III/IV disease, 36% had progression of disease ≤ 24 mo of initiation of first-line immunochemotherapy, 39% had refractory disease, and 22% had bulky disease. MZL subtypes included nodal (48%), splenic (27%), and extranodal/mucosa-associated lymphoid tissue (25%). Median (range) prior lines of therapy was 3 (2–18). Median (range) on-study follow-up was 24.1 mo (1.1–43.0). The primary endpoint of ORR was met at 95.5% (95% CI: 87.3–99.1; 1-sided &lt;i&gt;p&lt;/i&gt; &lt; 0.0001; Table). The secondary endpoint of CR rate was also met at 62.1% (95% CI: 49.3–73.8; 1-sided &lt;i&gt;p&lt;/i&gt; &lt; 0.0001; Table). With a median follow-up of 21.6, 23.8, and 24.5 mo, respectively, the 24-mo rates were 88.6% for DOR (89.0% in pts with CR), 85.7% for PFS, and 90.4% for OS (Table).&lt;/p&gt;&lt;p&gt;All pts had any-grade (gr) treatment-emergent adverse events (TEAE; gr ≥ 3, 88%). Cytokine release syndrome (CRS) occurred in 76% of pts (gr 3, 4%; no gr 4–5) and neurological events (NE) in 33% (gr 3, 4%; no gr 4–5; Table). For CRS/NE management, 33% of pts received both tocilizumab and corticosteroids, 21% received tocilizumab only, and 6% received corticosteroids only. Prolonged cytopenia (gr ≥ 3 laboratory values at Day 29) occurred in 42% of pts (anemia, 9%; neutropenia, 27%; thrombocytopenia, 25%), gr ≥ 3 infection in 9%, and MAS-HLH in 4% (all gr 3 and resolved). Two grade 5 TEAEs occurred (1 on Day 32, pt had T-cell lymphoma [TCL]; 1 on Day 47, pt had neutropenic sepsis). Liso-cel transgene testing and integration site analysis suggested that the TCL was unrelated to liso-cel.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusion:&lt;/b&gt; In pts with R/R MZL, liso-cel demonstrated deep and durable responses with high survival rates at 24 mo. The safety profile of liso-cel was manageable, with low rates of gr 3 CRS/NE ","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_55","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299721","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":"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,&nbsp;L. Conte,&nbsp;N. Shokun,&nbsp;M. Civallero,&nbsp;G. Hapgood,&nbsp;M. Prince,&nbsp;E. Miranda,&nbsp;C. Chiattone,&nbsp;M. E. Cabrera,&nbsp;A. Pavlovsky,&nbsp;F. Hits,&nbsp;T. Skrypets,&nbsp;S. M. Rodriguez Pinilla,&nbsp;F. Francine,&nbsp;R. Advani,&nbsp;J. Vose,&nbsp;M. Federico","doi":"10.1002/hon.70094_388","DOIUrl":"https://doi.org/10.1002/hon.70094_388","url":null,"abstract":"&lt;p&gt;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.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; 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.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; 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.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; 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.&lt;/p&gt;&lt;p&gt;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.&lt;/p&gt;&lt;p&gt;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 (&lt;i&gt;p&lt;/i&gt; &lt; 0.001).&lt;/p&gt;&lt;p&gt;Univariate analysis identified age &gt; 60 yrs (&lt;i&gt;p&lt;/i&gt; &lt; 0.001), stage III-IV (&lt;i&gt;p&lt;/i&gt; &lt; 0.001), ECOG ≥ 1 (&lt;i&gt;p&lt;/i&gt; &lt; 0.001), LDH &gt; UNL (&lt;i&gt;p&lt;/i&gt; &lt; 0.001), hemoglobin &lt; 12 g/dL (&lt;i&gt;p&lt;/i&gt; &lt; 0.001), platelets &lt; 150 g/L (&lt;i&gt;p&lt;/i&gt; &lt; 0.001), albumin &lt; 35 g/L (&lt;i&gt;p&lt;/i&gt; = 0.01), histotype (ALCL- vs. PTCL-NOS or AITL: &lt;i&gt;p&lt;/i&gt; &lt; 0.001), IPI ≥ 2 (&lt;i&gt;p&lt;/i&gt; &lt; 0.001), and PIT ≥ 2 (&lt;i&gt;p&lt;/i&gt; &lt; 0.001) as significant negative prognostic factors for both OS and PFS.&lt;/p&gt;&lt;p&gt;In the multivariate analysis, histotype, age &gt; 60 yrs, and stage III-IV emerged as independent prognostic factors for both OS and PFS (&lt;i&gt;p&lt;/i&gt; &lt; 0.001). Additionally, low PLT count was a significant independent predictor of worse PFS (&lt;i&gt;p&lt;/i&gt; &lt; 0.01).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; 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,&nbsp;M. Cai,&nbsp;Z. Li,&nbsp;Y. Shuang,&nbsp;H. Wu,&nbsp;Q. Zhang,&nbsp;J. Ma,&nbsp;H. Zhou,&nbsp;Y. Li,&nbsp;K. Zhou,&nbsp;P. Li,&nbsp;W. Qian,&nbsp;W. Yang,&nbsp;S. Zhou,&nbsp;X. Jia,&nbsp;L. Jiao,&nbsp;J. Wangwu,&nbsp;X. Luo,&nbsp;C. Guan,&nbsp;D. Chen,&nbsp;S. Fan,&nbsp;M. M. Shi,&nbsp;W. Su,&nbsp;W. Zhao","doi":"10.1002/hon.70093_163","DOIUrl":"https://doi.org/10.1002/hon.70093_163","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Introduction:&lt;/b&gt; 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.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; 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).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; 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.&lt;/p&gt;&lt;p&gt;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.&lt;/p&gt;&lt;p&gt;Genomic characteristics were assessed in 22 pts. &lt;i&gt;TET2&lt;/i&gt; (55%) was the most prevalent mutation, followed by &lt;i&gt;PCLO&lt;/i&gt; (32%), &lt;i&gt;HIST1H1E&lt;/i&gt; (27%), &lt;i&gt;CSMD1&lt;/i&gt; (23%), and &lt;i&gt;RHOA&lt;/i&gt; (23%). ORR of 100% was observed in 5 pts with &lt;i&gt;TET2&lt;/i&gt; and &lt;i&gt;RHOA&lt;/i&gt; co-mutations. &lt;i&gt;CSMD1&lt;/i&gt; and &lt;i&gt;RHOA&lt;/i&gt; mutations were mutually exclusive. &lt;i&gt;CSMD1&lt;/i&gt; alteration was associated with low ORR of 20%.&lt;/p&gt;&lt;p&gt;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 (&gt; 10%) grade ≥ 3 TRAEs were neutropenia (24.1%), anaemia (17.2%), lymphopenia (13.8%), and thrombocytopenia (13.8%). No treatment-related death occurred.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; 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,&nbsp;F. P. Gardner,&nbsp;A. C. de Oliveira,&nbsp;J. Sancho,&nbsp;E. Lomaia,&nbsp;D. Wright,&nbsp;M. Turgut,&nbsp;E. Martynova,&nbsp;Z. Lázár,&nbsp;B. Anz,&nbsp;M. Wang,&nbsp;W. Legiec,&nbsp;S. Opat,&nbsp;J. Pailden,&nbsp;H. M. Peltier,&nbsp;E. Marturano,&nbsp;J. P. Dean,&nbsp;I. W. Flinn","doi":"10.1002/hon.70093_26","DOIUrl":"https://doi.org/10.1002/hon.70093_26","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Introduction:&lt;/b&gt; 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.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; 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&lt;sup&gt;2&lt;/sup&gt; 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.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; In total, 445 pts were assigned to receive Ibr-R (&lt;i&gt;n&lt;/i&gt; = 334) or Pbo-R (&lt;i&gt;n&lt;/i&gt; = 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]; &lt;i&gt;p&lt;/i&gt; = 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]; &lt;i&gt;p&lt;/i&gt; = 0.004) and 4-y OS rates were 67% versus 71% (HR 1.12 [95% CI 0.77–1.63]; &lt;i&gt;p&lt;/i&gt; = 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.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; 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}