Hematological Oncology最新文献

{"title":"ANALYSIS OF COVID-19 INFECTIONS WITH FIXED-DURATION ACALABRUTINIB-VENETOCLAX COMBINATIONS IN TREATMENT-NAIVE CHRONIC LYMPHOCYTIC LEUKEMIA IN THE PHASE 3 AMPLIFY TRIAL","authors":"J. R. Brown, A. P. Kater, W. Jurczak, P. Ghia, B. Eichhorst, A. C. Peters, M. A. Pavlovsky, M. Yağcı, D. Lysak, K. Miller, T. Fujimori, S. Rule, M. de Borja, J. F. Seymour","doi":"10.1002/hon.70094_218","DOIUrl":"https://doi.org/10.1002/hon.70094_218","url":null,"abstract":"<p><b>Introduction:</b> An interim analysis of the ongoing phase 3 AMPLIFY trial (NCT03836261) showed significant progression-free survival benefit with both fixed-duration acalabrutinib-venetoclax combinations (± obinutuzumab; AV and AVO) versus investigator’s choice of fludarabine-cyclophosphamide-rituximab (FCR) or bendamustine-rituximab (BR) in patients (pts) with treatment (tx)-naive (TN) chronic lymphocytic leukemia (CLL), with initial data on COVID-19 adverse events (AEs) reported (Brown JR, et al., <i>NEJM</i>. 2025). We sought to further characterize COVID-19 AEs in AMPLIFY.</p><p><b>Methods:</b> Pts with TN CLL aged ≥ 18 y with ECOG ≤ 2 and without del(17p) or <i>TP53</i> mutation were randomized 1:1:1 to receive AV (oral acalabrutinib 100 mg BID [cycles (C) 1–14]; oral venetoclax QD [C3–14 with 5-wk dose ramp-up]), AVO (AV dosing as above, + intravenous obinutuzumab 1000 mg C2 [days 1, 8, and 15] and 3−7 [day 1]), or investigator’s choice of FCR or BR (C1−6). We report incidences of COVID-19 infections and deaths (during the tx-emergent period [up to earliest of 30 d after last dose or start of subsequent therapy] and up to the time of interim analysis [30 Apr 2024]), COVID-19 vaccination status, and COVID-19 deaths by pandemic waves.</p><p><b>Results:</b> In total, 867 pts were randomized from 2019 to 2021, including 291, 286, and 290 in the AV, AVO, FCR/BR arms, respectively, among whom 53.3% (AV), 50.0% (AVO), and 38.6% (FCR/BR) had ≥ 1 COVID-19 vaccination, most commonly tozinameran (Pfizer) in 35.4%, 31.5%, and 23.4% of pts. Among the 867 randomized pts, 321 had ≥ 1 COVID-19 event anytime during the trial, including 109 (37.5%), 131 (45.8%), and 81 (27.9%) pts in the AV, AVO, and FCR/BR arms, respectively, of whom 58.7%, 52.7%, and 12.3% experienced ≥ 1 event during the tx-emergent period. Median age among pts with ≥ 1 COVID-19 event was 60 y (23.1% > 65 y) versus 61 y (26.8% > 65 y) in the overall study population. Among study-treated pts (≥ 1 dose received), COVID-19 AEs were grade ≥ 3 in 29/291 (10.0%), 65/284 (22.9%), and 38/259 (14.7%) pts in the AV, AVO, and FCR/BR arms, respectively. COVID-19 AEs led to permanent discontinuation of ≥ 1 study tx in the regimen in 2.4% (AV), 8.1% (AVO), and 1.2% (FCR/BR) of pts. Death due to COVID-19 any time during the trial occurred in 10 (3.4%), 25 (8.7%), and 21 (7.2%) pts in the AV, AVO, and FCR/BR arms, respectively (of which 80.0%, 60.0%, and 33.3%, respectively, occurred during the tx-emergent period). Vaccination rates among all pts who died from COVID-19 were 0% (AV), 24.0% (AVO), and 9.5% (FCR/BR). COVID-19 death rates were highest during the second pandemic wave, with the highest rates in the AVO and FCR/BR arms (Figure).</p><p><b>Conclusions:</b> In this post hoc analysis, COVID-19–associated deaths occurred most frequently in the AVO and FCR/BR arms, followed by the AV arm. Vaccination rates were lower among pts with COVID-19 death versus overall. COVID-19 deaths were most","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_218","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299922","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":"PRELIMINARY RESULTS OF THE ONGOING MULTICENTER, PHASE 2 STUDY OF RETREATMENT WITH VENETOCLAX PLUS OBINUTUZUMAB (ReVenG) IN PATIENTS WITH RECURRENT CLL","authors":"M. S. Davids, S. Robrecht, E. Tausch, S. Stilgenbauer, M. Choi, A. Skarbnik, C. Chyn Chua, L. Sivcheva, K. Kreuzer, M. Ritgen, T. Gaska, D. Heintel, C. Arrais-Rodrigues, R. Santucci Alves Da Silva, T. Illmer, Z. Liu, B. Chyla, W. Sinai, M. V. Pai, M. Porro Lurà, M. Hallek, B. Eichhorst, O. Al-Sawaf, K. Fischer","doi":"10.1002/hon.70094_211","DOIUrl":"https://doi.org/10.1002/hon.70094_211","url":null,"abstract":"<p><b>Introduction:</b> Venetoclax (Ven)-based retreatment of patients (pts) with recurrent CLL after frontline Ven has not previously been studied prospectively. Here, we report an exploratory, interim analysis of the ongoing ReVenG trial, the first prospective study of Ven-Obinutuzumab (Obi) retreatment.</p><p><b>Methods:</b> CLL pts are eligible for this study (NCT04895436) if they received first-line (1L), time-limited Ven-based therapy, achieved response of ≥ 12 months (mo.) after completing therapy, then progressed and met iwCLL treatment criteria. Cohort-1 (Co-1, main cohort) includes pts with progressive (PD) > 2 years after completing 1L treatment (planned <i>N</i> = 60), and cohort-2 (Co-2, exploratory cohort) includes pts with PD 1 to 2 years post 1L therapy (planned <i>N</i> = 15). Both cohorts receive 6 cycles of Ven-Obi, with Co-1 receiving 12 total cycles of Ven, and Co-2 receiving at least 24 cycles of Ven. The primary endpoint is overall response rate (ORR) 3 mo. after the end of combination therapy (EOCT + 3 mo.) for Co-1. Key secondary endpoints include safety, additional response and MRD endpoints, and PFS.</p><p><b>Results:</b> At data cut-off of 18 October 2024, 25 of 75 pts (33%) were enrolled, 22 in Co-1 and 3 in Co-2. The median age was 67 years (range 41–84), with 76% Binet stage B or C. 32% had lymph nodes ≥ 5 cm at study entry. Median time to starting study treatment after last dose of 1L treatment was 53.3 mo. (range 19–90). 8/21 (38%) were either <i>TP53</i>mut and/or del(17p), and 18/21 (86%) tested were IGHV unmutated Of the 21 pts assessed at time of PD after FD treatment with Ven in 1L, none had acquired a mutation in <i>BCL-2</i>. With regard to efficacy in Co-1, all 15 pts who have reached EOCT + 3 mo. to date have achieved response, including 3 pts with CR/CRi, 2 pts in PR with radiographic CR awaiting marrow biopsy, and 10 pts with PR. At EOCT + 3 mo., 11 of 13 pts with samples available had undetectable MRD in the peripheral blood by NGS (<i>n</i> = 2 at 10<sup>−4</sup>, <i>n</i> = 3 at 10<sup>−5</sup>, <i>n</i> = 6 at 10<sup>−6</sup>). 7 pts have reached end of treatment + 3 mo., including 3 in CR and 4 in PR. With a median follow-up time on study of 10.3 mo., one pt has progressed, and all 25 pts are alive. In the safety analysis in all 25 pts, the most common AEs were neutropenia (44%, including 28% Gr 3/4), diarrhea (28%), nausea (24%) and infusion related reaction (24%). Serious AEs occurred in 32% of pts, including 1 pt each with sinusitis, pancytopenia, lower respiratory tract infection, COVID-19, and sepsis. There were no Gr 4 infections, fatal AEs, or tumor lysis syndrome (TLS). 3 pts (12%) had dose reduction of Ven due to AEs, including 1 each due to neutropenia, diarrhea, and nausea, and none discontinued Ven due to toxicity.</p><p><b>Conclusions:</b> In this interim analysis of the initial pts on ReVenG, efficacy was observed, and the safety of Ven-Obi in these relapsed pts was similar to prio","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_211","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299960","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":"MONITORING CIRUCLATING TUMOR DNA IMPROVES EARLY RELAPSE DETECTION AFTER STANDARD OF CARE 2L+ AXI-CEL IN LBCL: A PROSPECTIVE STUDY","authors":"S. Ananth, J. Mallampet, B. Chang, N. Agarwal, K. Kong, B. Sahaf, C. Lohman, N. Hossain, J. C. Cancilla, A. Bukhari, E. Dean, J. Speigel, I. Kirsch, A. Jacob, H. Simmons, L. W. Lee, J. Bacigalupi, C. Mackall, A. Rapoport, M. D. Jain, S. Dahiya, F. L. Locke, D. Miklos, M. Frank","doi":"10.1002/hon.70094_427","DOIUrl":"https://doi.org/10.1002/hon.70094_427","url":null,"abstract":"<p><b>Introduction:</b> Large B-cell lymphoma (LBCL) circulating tumor DNA (ctDNA)-based measurable residual disease (MRD) assessment is a prognostic tool for outcomes following CD19-CAR T-cell therapy and frontline treatment. CtDNA can risk stratify and predict outcomes providing additive benefit to standard PET-CT assessments for 3L+ Axicabtagene Ciloleucel (axi-cel, Frank et al., <i>JCO</i> 2021). The role for ctDNA monitoring for 2L axi-cel is unknown. Here, we present a prospective ctDNA analysis of 2L+ axi-cel patients with 6+ months (mo) of follow-up and compare this analysis to prior 3L+ data.</p><p><b>Method:</b> Plasma was collected from patients with LBCL receiving standard-of-care axi-cel at pre-lymphodepletion (PLD), days 14, and 28, totaling 222 plasma samples. (VDJ) clonotype (Clono-Seq) was identified from archival paraffin-embedded tissue to track MRD. PET-CT scans were performed before and at 1, 3, 6, and 12 mo post axi-cel; responses assessed per Lugano criteria (Deauville 1–3 was considered PET-negative). Any detectable ctDNA was considered detectable MRD. Significance for PFS was determined by log-rank <i>p</i> values and prognostic value of ctDNA was evaluated by a Cox proportional hazards model.</p><p><b>Results:</b> Patients in 2L+ (<i>n</i> = 84 enrolled 2022–2024) versus 3L+ (<i>n</i> = 64, enrolled 2018–2019) were median age of 65 (23–83) versus 59 (19–76), 61% versus 56% male, 55% versus 60% had elevated LDH, 73% versus 72% Stage 3/4, median 1 (1–5) versus 3 (1–7) prior lines (60% vs. 3% only 1 prior line; 12 % vs. 58% for 3+ prior lines). 60% (<i>n</i> = 50) versus 55% (<i>n</i> = 35) of 2L+ versus 3L+ patients received bridging. Median follow-up for 2L+ versus 3L+ was 18 versus 11 mo. Polatuzumab-based bridging (48% vs. 0%) was more common in 2L+; similar rates received radiation (36% vs. 26%). 2L+ versus 3L+ showed lower median PLD ctDNA levels (1.606307 [0–35,248] versus 63 [0–17,903] LG/mL) and a higher proportion of patients with undetectable MRD (uMRD) (38% vs. 26%) (Panel A). Lower levels of ctDNA suggests improved disease control and more effective bridging therapy in the 2L+ era.</p><p>For 2L+, ctDNA levels were prognostic before and at all time points in the early post-CAR-T setting. UMRD was associated with improved outcomes at all timepoints, including PLD (<i>p</i> = 0.04, HR 2.866, 1.287–6.382), Day 14 (<i>p</i> < 0.0001, HR 5.302, 2.342–12.00) and Day 28 (<i>p</i> = 0.001, HR 5.778, 2.606–12.81) (Panel A). PLD MRD levels did not associate with CRS or ICANS grade (not shown). MRD status at Day 14 and 28 stratified patients after 2L+ axi-cel (Panel B-C); uMRD was significantly associated with improved PFS. Patients with Day 28 radiographic PR/SD with uMRD (<i>n</i> = 12) versus detectable MRD (dMRD, <i>n</i> = 10) had improved PFS; 92% versus 40% of uMRD versus dMRD patients had durable remissions (panel D).</p><p><b>Conclusion:</b> This prospective study shows ctDNA assessments can predict for progres","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_427","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299984","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":"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}