Hematological Oncology最新文献

{"title":"THREE-HOUR INFUSION OF METHOTREXATE AT 3 g/m2 SIGNIFICANTLY REDUCES CNS RELAPSES AND IMPROVES SURVIVAL IN PATIENTS WITH LARGE B-CELL LYMPHOMAS AND INCREASED CNS RISK","authors":"A. J. M. Ferreri, F. Erbella, P. Angelillo, M. V. Ponti, L. Saliani, L. Pecciarini, L. Bongiovanni, T. Calimeri, A. Nonis, M. G. Cangi, F. Marino, E. Flospergher, G. Cassanello, P. Fiore, F. Palumbo, M. Ponzoni","doi":"10.1002/hon.70094_338","DOIUrl":"https://doi.org/10.1002/hon.70094_338","url":null,"abstract":"<p><b>Background</b>: A few recent studies questioned the effectiveness of high-dose methotrexate (MTX) in preventing CNS relapse in large B-cell lymphomas (LBCL); however, they suffer from biases, such as unbalanced distribution of patients (pts) with high-risk extranodal disease and lack of complete information on MTX dosing schedules and CNS events. We reviewed a large, single-centre cohort of LBCL pts treated with uniform CNS-directed MTX dosing schedule, aiming to demonstrate its favourable effect on CNS recurrence and survival in pts with high CNS risk, as defined by recent consensus criteria (Eyre T, et al., <i>Lancet Oncol</i> 2022).</p><p><b>Methods</b>: We reviewed 501 LBCL pts treated from 2002 to 2021, focusing on those who achieved complete metabolic remission (CMR) after upfront RCHOP or similar. Pts at high CNS risk, as defined by our institution’s criteria, received 2 (stage I-II) or 3 (advanced stage) doses of MTX (3 g/m<sup>2</sup> over 3 hours, preceded by a fast bolus) after RCHOP. Histological specimens were reviewed, diagnoses updated according to the latest WHO/ICC classifications, and CNS risk reassessed using recent consensus criteria (CNS-IPI ≥ 4, ≥ 3 extranodal sites, or involvement of the testis, kidney, adrenal gland, or breast). MTX’s effect on CNS recurrence was assessed using Gray’s test, treating other events (systemic recurrence, unrelated death) as competing risks. MTX’s impact on PFS and OS was also assessed.</p><p><b>Results</b>: 344 pts in CMR after RCHOP or similar were considered. CNS risk according to recent criteria was low in 231 (66%) pts and high in 113 (33%); MTX was given to 17 (7%) and 49 (43%) pts, respectively. After a median follow-up of 75 months (IQR 54–102), CNS relapse occurred in 13 (4%) pts, always as isolated site: brain (10), meninges (2), and cranial nerves (1). Among low-risk pts, CNS relapse rate was 2% (4/214) without MTX and 0% (0/17) with MTX. In high-risk pts, this rate was 14% (9/64) without MTX and 0% (0/49) with MTX, yielding a 4-year cumulative CNS relapse rate of 18% and 0%, respectively (<i>p</i> = 0.003). The most notable MTX benefit was seen in 62 pts with involvement of testes, kidneys, or adrenal gland, where CNS relapse rate dropped from 23% (7/31) to 0% (0/31) (<i>p</i> = 0.01), and in 66 pts with ≥ 3 extranodal sites, where rate dropped from 13% (5/38) to 0% (0/28) (<i>p</i> = 0.06). MTX also was associated with improved PFS and OS in the 113 high-risk pts (independent in multivariable analysis). In these pts, also event distribution suggested MTX’s role in prophylaxis: 8 (12%) unrelated deaths, 13 (20%) systemic relapses, and 9 (14%) CNS relapses occurred in the 64 pts treated without MTX, whereas 4 (8%) unrelated deaths, and 9 (18%) systemic relapses, with no CNS relapses, occurred in the 49 treated with MTX.</p><p><b>Conclusion</b>: MTX (3 g/m<sup>2</sup> over 3 hs) significantly reduces CNS relapses and improves PFS and OS in LBCL pts with CNS-IPI ≥ 4, ≥ 3 extranod","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_338","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292663","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":"POPULATION-WIDE INTRODUCTION OF DOSE-ADJUSTED EPOCH-R IN HIGH-GRADE B-CELL LYMPHOMA WITH MYC AND BCL2 REARRANGEMENTS WITH DLBCL MORPHOLOGY","authors":"W. Alduaij, L. H. Sehn, J. Champagne, B. Collinge, S. Ben-Neriah, A. Jiang, L. K. Hilton, M. Boyle, B. Meissner, G. W. Slack, P. Farinha, J. W. Craig, K. J. Savage, D. Villa, A. S. Gerrie, C. L. Freeman, A. J. Mungall, C. Steidl, D. W. Scott","doi":"10.1002/hon.70093_75","DOIUrl":"https://doi.org/10.1002/hon.70093_75","url":null,"abstract":"<p><b>Introduction:</b> High-grade B-cell lymphoma with <i>MYC</i> and <i>BCL2</i> rearrangements (HGBCL-DH-<i>BCL2</i>) has poor outcomes after R-CHOP, prompting dose-intensive chemoimmunotherapy use. However, the benefit is unclear because rarity precluded randomized trials, and retrospective comparisons are confounded by variable selection of tumors for FISH testing and clinical factors influencing patient selection for intensification. In 2015, British Columbia, Canada introduced a population-based guideline to treat fit patients (pts) aged ≤ 75 years (y) with de novo HGBCL-DH-<i>BCL2</i> tumors of DLBCL morphology with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) alongside routine clinical FISH testing (DA-EPOCH-R era). To assess the impact of the DA-EPOCH-R guideline, we compared the outcomes of HGBCL-DH-<i>BCL2</i> with DLBCL morphology in the DA-EPOCH-R era to HGBCL-DH-<i>BCL2</i> identified from a historic province-wide cohort of DLBCL morphology tumors that underwent universal FISH testing in a research setting (historic era, Alduaij et al <i>Blood</i> 2023), while comparing outcomes of DLBCL, NOS treated with R-CHOP as a control population (Figure 1A). We evaluated the prognostic impact of molecular subgroups within HGBCL-DH-<i>BCL2</i>. Given the earlier onset of progression events in HGBCL-DH-<i>BCL2</i> than DLBCL, NOS after R-CHOP (Rosenwald et al <i>JCO</i> 2019), we compared the prognostic impact of end of treatment (EOT) PET between those entities in the DA-EPOCH-R era.</p><p><b>Methods:</b> Overall survival (OS) was analyzed using Kaplan-Meier with log-rank comparisons. <i>MYC</i>-rearrangement partner loci were determined by breakpoint capture sequencing. DLBCL90 digital gene expression defined dark-zone signature (DZsig) status. EOT response was assessed by the Deauville criteria for positive (D4–5, POS), and negative (D1–3 or X, NEG) scans.</p><p><b>Results:</b> HGBCL-DH-<i>BCL2</i> versus DLBCL, NOS pts were 66 versus 627 in the DA-EPOCH-R era, and 38 versus 534 in the historic era. 71% of HGBCL-DH-<i>BCL2</i> pts received DA-EPOCH-R in the DA-EPOCH-R era and 84% received R-CHOP in the historic era. Median (interquartile range) follow-up was 6.2 (5.0–7.6) y in the DA-EPOCH-R era and 15.7 (13.8–16.0) y in the historic era. OS was significantly higher in the DA-EPOCH-R era (2y: 75% versus 47%, <i>p =</i> 0.008, Figure 1B). No difference in 2y OS was found between eras in DLBCL, NOS (78% vs. 76%, <i>p =</i> 0.17, Figure 1C). Among evaluable HGBCL-DH-<i>BCL2</i> tumors, 43% had <i>IG: MYC</i> and 77% expressed DZsig, both associated with higher 2y OS in the DA-EPOCH-R versus historic era (<i>IG: MYC</i>: 87% vs. 36%, <i>p</i> = 0.01, DZsig: 70% vs. 40%, <i>p</i> = 0.02). 2y OS stratified by EOT PET was similar in HGBCL-DH-<i>BCL2</i> (NEG: 93% vs. POS: 62% <i>p</i> = 0.006) and DLBCL, NOS (NEG: 90% vs. POS: 62% <i>p</i> < 0.0001).</p><p><b>Conclusion:</b> Introdu","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_75","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292683","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":"REAL-WORLD OUTCOMES OF PIRTOBRUTINIB IN RELAPSED/REFRACTORY MANTLE CELL LYMPHOMA: A MULTICENTER ANALYSIS WITH A CONTROL COHORT FROM THE EUROPEAN MCL REGISTRY","authors":"E. Aydilek, F. Schwarz, L. Simon, P. Dreger, E. Shumilov, G. Lenz, V. Vucinic, E. Silkenstedt, R. D. Jachimowicz, C. Pott, M. Tometten, C. Leng, M. Ahlborn, F. Müller, M. Maulhardt, G. Wulf, M. Voegeli, K. Sohlbach, K. Schäfer-Eckart, T. Gaska, R. Greil, I. Kohl, S. Wirths, S. Stilgenbauer, D. Hartnack, M. Topp, S. Dietrich, C. Renner, G. Reiff, P. Marschner, J. Hauser, F. Klaus, M. Bartkowiak, R. Reihs, M. Gomes da Silva, A. Ohler, G. Heß","doi":"10.1002/hon.70094_273","DOIUrl":"https://doi.org/10.1002/hon.70094_273","url":null,"abstract":"<p>E. Aydilek, F. Schwarz, and L. Simon equally contributing author.</p><p><b>Introduction:</b> Pirtobrutinib (P), a highly selective, non-covalent BTK inhibitor (BTKi), has shown promising results in the BRUIN trial for relapsed/refractory mantle cell lymphoma (r/r MCL). However, there are limited data outside clinical trials, which would be helpful to understand the full impact of this novel approach. To address this knowledge gap, we analyzed real-world outcomes of patients treated with P with the named patient program in Germany and additional patients from the European Mantle Cell Lymphoma (EMCL) registry.</p><p><b>Methods:</b> We identified 63 patients in the EMCL registry from Germany, Switzerland, Austria, and Portugal with r/r MCL who received P. Primary endpoints were treatment intent (bridging/definite) overall response rate (ORR), efficacy to bridge for consolidation with chimeric antigen receptor (CAR) T-cells and overall survival (OS). Survival outcomes were compared using the log-rank test for overall OS and chi-square test at appropriate follow-up times (FUT). Median FUT was estimated with the reverse KM method. A data cut-off as of 10.03.2025 was used, and updated results will be presented. In addition, results were compared to the results obtained with preceding BTKi-therapy.</p><p><b>Results:</b> Median age at treatment start of P was 72 years (range: 45–86 y), with a median time since diagnosis of 5.75 years (range: 0.3–24 y). Patients were predominantly male (75.8%, 47/62 (result/number with available information)). At treatment initiation with P, clinical characteristics included ECOG ≥ 2 in 27% (13/48), Ki-67 ≥ 30% in 82% (18/22), blastoid or pleomorphic morphology in 37% (15/41), <i>TP53</i> mutations in 60% (15/25) and 3 median lines of prior therapy (range: 1–11). 97% of patients (61/63) had prior ibrutinib (I) treatment, 37% (23/63) autologous transplantation, 8% (5/63) allogeneic transplantation or had receive prior CAR-T therapy 13% (8/63). The majority received P monotherapy (92%, 45/49). After a median FUT of 5.2 months (range: 0.2–30.4 month), 78% (49/63) showed no progression on P. OS probability was 50.1% at two years. P was used as bridging therapy before CAR-T in 49% (24/49) of cases. When comparing results of P with I without subsequent CAR-T therapy, we observed a comparable ORR (57.8% vs. 53.9%), with no significant differences in overall OS (<i>p</i> = 0.74) or at one or two years FUT (1-year: <i>p</i> = 0.9; 2-year: <i>p</i> = 0.16). However, in the group of patients without CAR-T-consolidation (<i>n</i> = 17) ORR tended to be lower 50% (7/14).</p><p><b>Conclusion:</b> In this real-world cohort with adverse patient characteristics P was effective with a higher ORR (57.8% vs. 49.3%) and similar CR rates (17.7% vs. 15.8%) as in the BRUIN trial. Interestingly, in this preliminary analysis subsequent P therapy after prior I treatment did not result in a decrease in response and disease control. Utilization as ","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_273","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292721","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":"PD-1-BASED SALVAGE THERAPY FOR RELAPSED AND REFRACTORY HODGKIN LYMPHOMA: A MULTICENTER REAL-WORLD ANALYSIS","authors":"H. Tharmaseelan, L. M. Sgonina, I. Bühnen, U. Schnetzke, J. Meißner, M. Sellmayr, D. Beverungen, J. C. Hellmuth, E. Shumilov, A. Kerkhoff, T. Melchardt, P. J. Bröckelmann, P. Borchmann, B. von Tresckow","doi":"10.1002/hon.70094_358","DOIUrl":"https://doi.org/10.1002/hon.70094_358","url":null,"abstract":"<p><b>Introduction:</b> In relapsed/refractory classical Hodgkin lymphoma (r/r cHL), salvage therapy with chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (HD-ASCT) yields suboptimal long-term outcomes, with 5-year progression-free survival (PFS) rates below 50%.</p><p>PD-1 inhibitor-based salvage regimens have shown superior complete response (CR) rates. For example, P-GVD (pembrolizumab, gemcitabine, vinorelbine, liposomal doxorubicin) achieved CR rates of up to 95% with unprecedented PFS after HD-ASCT (Moskowitz et al., <i>JCO</i> 2021). However, immune checkpoint inhibitors are not EMA-approved for first relapsed in r/r cHL, and European data remain sparse. We evaluated response and outcomes in a European real-world cohort of r/r cHL patients receiving anti-PD-1–based salvage.</p><p><b>Methods:</b> This multicenter, retrospective study included patients from seven European academic centers who received PD-1–based salvage with intent to proceed to HD-ASCT or allogeneic SCT (alloSCT). Response before HD-ASCT/alloSCT was assessed. PFS and overall survival (OS) were estimated using Kaplan-Meier analysis.</p><p><b>Results:</b> We included 43 patients (median age: 31 years, 37.2% female, median prior lines: 2). Salvage regimens were: (I) PD-1 monotherapy (pembrolizumab/nivolumab, <i>n</i> = 7), (II) PD-1 plus chemotherapy [pembrolizumab or nivolumab plus ifosfamide, carboplatin, and etoposide (N-ICE/ P-ICE) or P-GVD, <i>n</i> = 33], or (III) PD-1 (pembrolizumab/nivolumab) + brentuximab vedotin (<i>n</i> = 3).</p><p>Overall response rate (ORR) was 92.5%, with 47.5% achieving CR, 45% partial response (PR), and 7.5% stable disease (SD) (40 evaluable patients). BOR/CR rates by salvage regimen were (I): 85.7%/0%; (II): 93.3%/60% (30 evaluable patients); (III): 100%/33.3%. Patients with one prior line receiving PD-1 plus chemotherapy had an ORR of 95% to salvage, with a CR rate of 55%.</p><p>Among 40 patients proceeding to HD-ASCT/alloSCT (six alloSCT), best overall response (BOR) and CR rates after transplant were 100% and 96.8% (31 evaluable patients).</p><p>With a median follow-up of 15.5 months, 1-year PFS was 91.3% (95% CI: 81.7–100) and OS was 97.6% (95% CI: 93–100). Patients undergoing HD-ASCT/alloSCT (<i>n</i> = 40) had a 1-year PFS of 93.8% (95% CI: 85.4–100) versus 50% (95% CI: 0–100) without transplant. Patients receiving PD-1 plus chemotherapy followed by HD-ASCT in second line had a 1-year PFS of 100% (95% CI: 100–100).</p><p><b>Conclusion:</b> Our findings provide real-world evidence on anti-PD-1–based salvage followed by intensive consolidation in European centers. While previously reported high CR rates after PD-1–based salvage were not reached, outcomes post-HD-ASCT were excellent, supporting the role of PD-1 inhibitors in salvage therapy followed by consolidation HD-ASCT for r/r cHL.</p><p><b>Encore Abstract:</b> EHA 2025</p><p><b>Keywords:</b> Hodgkin lymphoma; immunotherapy</p><p><b>Potential so","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_358","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292827","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":"DIFFUSE LARGE B-CELL LYMPHOMA IN BRAZIL: A COMPREHENSIVE ANALYSIS OF SOCIODEMOGRAPHIC PATTERNS","authors":"G. Duffles, D. Clé, D. Castro, N. F. Correa-Netto, C. S. K. La Scala, I. D. Silveira, R. Gaiolla","doi":"10.1002/hon.70094_300","DOIUrl":"https://doi.org/10.1002/hon.70094_300","url":null,"abstract":"<p><b>Introduction:</b> Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma, with around 60% of patients being progression-free in the long-term with standard treatment. Brazil is one of the largest countries in the world where 70% of the population is treated by the public health system (Sistema Único de Saúde—SUS). Considering the country disparities across different regions, there is a lack of studies focusing on sociodemographic aspects of patients with DLBCL.</p><p><b>Methods:</b> This is an observational, retrospective, descriptive study, based on real-world data extracted from the SUS service records (claim data), provided by the Information Department of Informatics of SUS (DATASUS). Patients 18 years old or more with a diagnosis of DLBCL, between 2015 and 2023 and treated with immunochemotherapy (rituximab-based) were included.</p><p><b>Results:</b> We analyzed 21876 patients. Median age at diagnosis was 59y (interquartile range = 23y) and most patients were between 60 and 69y (24.7%). There were 52.5% males and 52.1% whites. 61% of patients presented with advanced stage disease. During the study period, there was a steady increase of 0.6% in diagnosis per year. Most patients came from the southeast region of Brazil (42.7%), with the fewest proportion of localized disease (35.3%). Most cases had received treatment outside the city of residence (58.2%), especially in the country's northeast (62.4%). Ninety percent of patients received only immunochemotherapy and 8% combined treatment (with radiotherapy). Most patients received only first-line treatment (93.9%), while 12.5% and 3.9% received second and third lines of therapy. The mean number of cycles in the first, second, and third lines were 5.9, 4.7, and 5.0, respectively. Figure 1 illustrates a map of Brazil highlighting the regional differences across the country.</p><p><b>Conclusions:</b> This is the largest real-world study of DLBCL patients in Brazil. The southeast country's region has the majority of treating centers and hence most cases. It is common for patients to leave their homes to receive treatment, especially in poorer regions such as the northeast. Radiotherapy was rarely given as a treatment option. Most cases were treated in the first line, while the proportion in latter lines are very limited. Considering the accepted rate of progression-free survival with standard world-wide RCHOP, it seems that many patients treated in the public system do not have access to salvage treatment.</p><p><b>Research</b> <b>funding declaration:</b> None</p><p><b>Keywords:</b> Aggressive B-cell non-Hodgkin lymphoma; Cancer Health Disparities</p><p><b>Potential sources of conflict of interest:</b></p><p><b>D. Castro</b></p><p><b>Employment or leadership position:</b> Employee of Hoffmann-La Roche Ltd</p><p><b>N. F. Correa-Netto</b></p><p><b>Employment or leadership position:</b> Employee of Hoffmann-La Roche Ltd</p><p><b>C. S. K. La Scala</b></p><p><b>Employment or lead","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_300","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292834","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":"EXPLORING A NEW PROGNOSTIC INDEX IN 341 POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDERS IN THE “RITUXIMAB ERA”: A RETROSPECTIVE STUDY FROM SPANISH LYMPHOMA GROUP GELTAMO","authors":"D. Gil-Alós, R. Mancebo-Martín, S. Romero Domínguez, E. González-Barca, L. Magnano, F. de la Cruz, G. Iacoboni, C. Martínez Losada, S. Browne Arthur, R. Gil Manso, A. Rodríguez Izquierdo, T. Baumann, Á. López-Caro, M. Poza Santaella, A. García Bacelar, P. Gómez Prieto, D. Bermejo-Peláez, S. González de Villambrosi, P. Fernández Abellán, D. Brau-Queralt, F. Salido Toimil, M. E. Amutio, A. Cascales, M. Micó, S. Huerga Domínguez, B. de la Cruz Benito, M. Landwehr, I. Hernández de Castro, R. Andreu, J. Martínez-López, M. Luengo-Oroz, A. Jiménez-Ubieto","doi":"10.1002/hon.70094_378","DOIUrl":"https://doi.org/10.1002/hon.70094_378","url":null,"abstract":"<p>D. Gil-Alós and A. Jiménez-Ubieto equally contributing author.</p><p><b>Introduction:</b> Post-transplant lymphoproliferative disorders (PTLD) are life threatening malignancies that can develop as a complication following solid organ transplantation. Due to the risk of treatment-related complications, tailoring treatment to patients according to their risk profile could potentially improve outcomes even further. The aim of this study was to design a simple and practical prognostic model and to validate scores usually used in large b cell lymphoma in a large cohort of monomorphic PLTD patients.</p><p><b>Methods:</b> A total of 341 PTLD patients from 16 Spanish hospitals (2000–2024) were retrospectively included. 27 clinical and biological variables were collected, excluding 2 with > 35% missing data. The remaining missing values (∼7%) were imputed using KNN. Feature selection was performed using LASSO, followed by further refinement with the Elbow method of Shapley values, retaining the top 80% of cumulative feature importance. A random survival forest model was trained to develop the Artificial Intelligence-PTLD Prognostic Index (AI-PTLD-PI), using an 80/20 train-test split. The training underwent 5-fold cross-validation for hyperparameter tuning, followed by final model retraining and evaluation on the independent test set. The AI-PTLD-PI was compared with established scores (IPI, aaIPI, R-IPI, NCCN-IPI, GELTAMO-IPI, KPI, DLBCL-IPI, PTLD-IPI) using time-dependent AUC, C-index, and Brier score at 5 years.</p><p><b>Results:</b> Among the patients analyzed, 85% had B-cell monomorphic PTLD, mainly following kidney (42%) or liver transplantation (30%). The median time from transplant to lymphoma onset was 91 months (range: 1–393), and 41% of cases were EBV-related. The median follow-up was 5.7 years.</p><p>To assess prognostic accuracy, univariate Cox regression was applied to each index. The modified NCCN-IPI and PTLD-IPI showed the highest performance among standard scores (c-index: 0.672 and 0.639, respectively). Our AI-PTLD-PI outperformed all models, achieving a c-index of 0.736. In time-dependent analyses, AI-PTLD-PI consistently demonstrated superior prognostic value with a time-dependent AUC of 0.783. Detailed performance comparison is shown in Figure 1A,B.</p><p>For further validation, AI-PTLD-PI stratified patients into survival terciles (low, intermediate, high risk) (Figure 1C). AI-PTLD-PI showed a log-rank <i>p</i>-values of 0.09 (low vs. intermediate), 0.000002 (low vs. high), and 0.001 (intermediate vs. high), reinforcing its prognostic utility. Key prognostic factors in AI-PTLD-PI were found with a Shapley value analysis, highlighting older age at transplant and diagnosis, lower albumin, elevated LDH, and high lymphocyte count as major risk factors (Figure 1D).</p><p><b>Conclusion:</b> In this large PTLD series, the AI-PTLD-PI identify patients at higher risk of death with superior accuracy than other scores. The major risk fact","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_378","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292900","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":"DELIVERY OF EMERGENCY CARE FOR PATIENTS WITH LYMPHOMA IN A DEDICATED FACILITY BY ADVANCED NURSE PRACTITIONERS","authors":"M. Fowler","doi":"10.1002/hon.70093_ON01","DOIUrl":"https://doi.org/10.1002/hon.70093_ON01","url":null,"abstract":"<p><b>Introduction:</b> Patients with lymphoma often experience acute complications, including infections, disease progression, and treatment-related side effects, necessitating urgent medical attention. Traditional emergency departments may not provide optimal care due to long wait times and a lack of specialist haemato-oncology expertise. To address these challenges, our institution established a dedicated emergency care facility for all patients with cancer, staffed by advanced nurse practitioners (ANPs). This service aims to improve access to timely, expert-driven emergency care while reducing unnecessary hospital admissions.</p><p><b>Methods:</b> The dedicated emergency care facility is staffed by experienced ANPs with specialist haemato-oncology training. All ANPs have a dedicated MSc in Advanced Clinical Practice and the unit also supports trainee ANPs completing their MSc programme. The service operates 7 days per week, providing rapid assessment, symptom management, and coordination with haematology teams. ANPs perform comprehensive patient assessments, prescribe medications (including blood product authorisation), initiate diagnostics, manage acute complications, and determine appropriate interventions, including outpatient treatment, rapid specialist referrals, or hospital admission if necessary. A multidisciplinary approach ensures continuity of care and optimal patient outcomes.</p><p><b>Results:</b> Since its implementation, the service has enhanced the efficiency of emergency care for lymphoma patients. Wait times for assessment have significantly decreased, and hospital admission rates have been reduced by providing timely interventions in an ambulatory setting. The ANP-led model has improved patient satisfaction, with high ratings for accessibility, communication, and symptom management. Additionally, collaboration with haemato-oncology specialists has streamlined patient pathways, ensuring prompt escalation of care when needed.</p><p><b>Conclusions:</b> A dedicated ANP-led emergency care facility provides a safe, efficient, and patient-centered approach to managing lymphoma-related emergencies. This model enhances the quality of care while alleviating pressure on emergency departments. Its success highlights the critical role of ANPs in specialist acute haemato-oncology services, with potential for replication in other cancer centres.</p><p><b>Research</b> <b>funding declaration:</b> Nil</p><p><b>Keywords:</b> outpatient developments and ambulatory care</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_ON01","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292902","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":"UPDATED INTERIM RESULTS OF SONROTOCLAX + DEXAMETHASONE IN PATIENTS WITH T(11;14)-POSITIVE RELAPSED/REFRACTORY MULTIPLE MYELOMA (R/R MM): AN ALL-ORAL TREATMENT","authors":"B. Dhakal,&nbsp;M. Hultcrantz,&nbsp;N. Nathwani,&nbsp;C. P. Venner,&nbsp;J. Lu,&nbsp;M. J. Slade,&nbsp;J. L. Kaufman,&nbsp;H. Chuah,&nbsp;C. Min,&nbsp;K. Kim,&nbsp;H. Cheng,&nbsp;A. Idoine,&nbsp;W. Zhang,&nbsp;X. Wang,&nbsp;A. Agarwal,&nbsp;H. Quach","doi":"10.1002/hon.70093_123","DOIUrl":"https://doi.org/10.1002/hon.70093_123","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Introduction:&lt;/b&gt; Despite the clinical efficacy of BCL2 inhibition in t(11;14)-positive MM, no BCL2-targeted treatments (tx) are approved. Sonrotoclax (sonro; BGB-11417), a next-generation BCL2 inhibitor, is a more selective and pharmacologically potent inhibitor of BCL2 than venetoclax, with a shorter half-life and no drug accumulation. BGB-11417-105 (NCT04973605) is an ongoing phase 1b/2 study of sonro as mono- or combination tx in patients (pts) with t(11;14)-positive R/R MM. Updated results in pts treated with sonro + dexamethasone (dex) are presented.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; Eligible pts had R/R MM with centrally confirmed t(11;14) and received oral sonro (320 or 640 mg QD) + dex (40 mg QW). Tx-emergent adverse events (TEAEs) were graded by CTCAE v5.0 and efficacy was assessed by the investigator per IMWG criteria.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; As of January 20, 2025, 14 and 36 evaluable pts were enrolled in the sonro 320-mg and 640-mg cohorts, respectively; median (range) follow-up was 6.2 mo (2.6–34.5) and 12.1 mo (0.1–28.9), respectively. The median (range) prior lines of tx were 3 (1–7) in the 320-mg cohort and 3 (1–12) in the 640-mg cohort; 78.6% and 66.7% of pts were refractory to 3 tx classes, respectively. At data cutoff, 7 pts (50.0%) in the 320-mg cohort and 14 (38.9%) in the 640-mg cohort remained on tx; progression was the most common reason for discontinuation (35.7% and 41.7%, respectively). The ORR (95% CI) was 64.3% (35.1–87.2) in the 320-mg cohort and 80.6% (64.0–91.8) in the 640-mg cohort, with VGPR or better rates (95% CI) of 35.7% (12.8–64.9) and 55.6% (38.1–72.1), respectively (Figure). The median time to response was 0.7 mo in both cohorts. Median (95% CI) duration of response was 5.9 mo (1.8-not estimable [NE]) in the 320-mg cohort and 12.2 mo (8.3–18.9) in the 640-mg cohort. Median (95% CI) PFS was 6.6 mo (2.9-NE) in the 320-mg cohort and 13.3 mo (9.0–19.6) in the 640-mg cohort.&lt;/p&gt;&lt;p&gt;The most common TEAEs were fatigue (35.7%) in the 320-mg cohort, and insomnia (38.9%) and diarrhea (38.9%, all grade 1/2) in the 640-mg cohort. Grade ≥ 3 TEAEs occurred in 5 pts (35.7%) in the 320-mg cohort and 17 pts (47.2%) in the 640-mg cohort; serious TEAEs occurred in 3 (21.4%) and 10 (27.8%), respectively. Grade ≥ 3 hematologic TEAEs occurred in 1 (7.1%) and 9 (25.0%) and grade ≥ 3 infections in 3 (21.4%) and 4 (11.1%) pts, respectively. Two pts (14.3%) in the 320-mg cohort and 2 (5.6%) in the 640-mg cohort died during the tx-emergent part for reasons unrelated to tx (320 mg, pneumonia RSV and COVID-19; 640 mg, hypoventilation [related to pulmonary involvement with PD] and metastatic pancreatic cancer). Four more deaths occurred &gt; 30 d after the last 640-mg dose.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; This ongoing study showed that the all-oral combination of sonro + dex is tolerable, with low rates of infection and hematologic toxicity, and promising efficacy, with an ORR of 81% in the 640-mg cohort, in this t(11;14)-positive R/R MM population.","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_123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292904","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":"NODAL MARGINAL ZONE LYMPHOMA: MUTATIONAL ANALYSIS, GENE EXPRESSION PROFILE, AND DIFFERENTIAL DIAGNOSIS FROM OTHER SMALL B-CELL LYMPHOMAS","authors":"V. Borgmann,&nbsp;H. S. Gierer,&nbsp;S. Paigin,&nbsp;I. Bonzheim,&nbsp;F. Fend,&nbsp;D. Nann,&nbsp;L. Quintanilla-Martinez","doi":"10.1002/hon.70094_253","DOIUrl":"https://doi.org/10.1002/hon.70094_253","url":null,"abstract":"&lt;p&gt;D. Nann equally contributing author.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Objective&lt;/b&gt;: Nodal Marginal zone lymphoma (NMZL) represents 1.5%–1.8% of NHL. NMZL diagnosis is based on a combination of morphological and immunophenotypic features. Due to the absence of disease-defining phenotypic/genetic markers in NMZL, the differential diagnosis with other NHL, especially &lt;i&gt;BCL2&lt;/i&gt; rearrangement-negative follicular lymphoma (&lt;i&gt;BCL2&lt;/i&gt;-R-neg FL) can be challenging. We performed mutational analysis to investigate whether these might help in separating NMZL from other small B-cell lymphomas. Additionally, NMZL GEP was compared to the genetic profile of &lt;i&gt;BCL2&lt;/i&gt;-R-neg FL obtained in a previous study.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Material and Methods:&lt;/b&gt; 52 cases with the diagnosis of NMZL were selected. All cases were comprehensively immunophenotyped. &lt;i&gt;BCL2&lt;/i&gt; and &lt;i&gt;BCL6&lt;/i&gt; FISH analyses were performed in selected cases. Targeted NGS analysis was done on the Ion GeneStudio S5 Prime (ThermoFisher). NGS libraries were amplified using a custom Oncomine lymphoma panel (ThermoFisher) covering 82 genes frequently mutated in B-cell NHL. GEP was performed using the nCounter PanCancer Immune profiling panel from NanoString.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; The 52 cases included 30 women and 22 men with a mean age of 67 years (range 36–89). After morphological and mutational analyses 38 cases were confirmed as NMZL (73%) and 14 cases (27%) were reclassified as a different NHL. The most difficult differential diagnosis was with &lt;i&gt;BCL2&lt;/i&gt;-R-neg FL (8/52; 15%), including four CD23+ cases harboring &lt;i&gt;STAT6&lt;/i&gt; mutations co-occurring with &lt;i&gt;CREBBP&lt;/i&gt; and/or &lt;i&gt;TNFRSF14&lt;/i&gt; mutations. The other 4 cases were reclassified as &lt;i&gt;BCL2&lt;/i&gt;-R-neg FL based on the expression of at least one GC marker and the mutational profile; 3 showed &lt;i&gt;BCL6&lt;/i&gt;-R. Six cases (6/52; 11.5%) were reclassified as CLL based on morphology and a mutational profile compatible with CLL (&lt;i&gt;ATM, BIRC3, NOTCH1, TP53&lt;/i&gt;). All 6 cases had an atypical phenotype, either CD5 and/or CD23 negativity. In 33/38 NMZL cases (87%), 118 pathogenic mutations were identified (3.57 mutation/per case). The most frequently mutated gene was &lt;i&gt;KLF2&lt;/i&gt; (13/38; 34%), followed by &lt;i&gt;KMT2D&lt;/i&gt; (8/38; 21%), &lt;i&gt;TBL1XR1&lt;/i&gt;, (6/38; 16%), &lt;i&gt;TET2, CREBBP&lt;/i&gt;, &lt;i&gt;HIST1H1E, BTG2, FAS&lt;/i&gt; (4/38; 11%), &lt;i&gt;MYD88, SPEN&lt;/i&gt;, &lt;i&gt;ARID1A, NOTCH2, TNFRSF14&lt;/i&gt; (3/38; 8%), &lt;i&gt;BCL10, ARID1B&lt;/i&gt;, &lt;i&gt;ID3, HLA-B, CD70, SOCS1,&lt;/i&gt; (2/38; 5%), and others (see figure). Unsupervised clustering of GEP correlated with the final pathological classification and separated NMZL from the &lt;i&gt;BCL2&lt;/i&gt;-R-neg FL &lt;i&gt;STAT6&lt;/i&gt; mut cases. However, some &lt;i&gt;BCL2&lt;/i&gt;-R-neg FL &lt;i&gt;STAT6&lt;/i&gt; wt cases clustered with NMZL. NMZL showed upregulation of genes involved in Toll receptor cascades (&lt;i&gt;TLR1, TLR7, MAP3K1&lt;/i&gt;), cytokine interactions (&lt;i&gt;TNFSF18, CXCR3, IL6, TNFRSF15, CCR6&lt;/i&gt;), and innate immune system.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Mutational analysis is useful for the differential diagnosis of NMZL","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_253","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292941","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":"MULTI-TARGETED THERAPY WITH VIPOR-P IN RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA: UPDATED ANALYSIS OF EFFICACY AND MINIMAL RESIDUAL DISEASE","authors":"C. Melani,&nbsp;R. Lakhotia,&nbsp;S. Pittaluga,&nbsp;J. D. Phelan,&nbsp;J. Muppidi,&nbsp;M. Gordon,&nbsp;Y. Yang,&nbsp;W. Xu,&nbsp;T. Davies-Hill,&nbsp;D. W. Huang,&nbsp;C. J. Thomas,&nbsp;M. Ceribelli,&nbsp;F. A. Tosto,&nbsp;A. M. Juanitez,&nbsp;A. Pradhan,&nbsp;C. Morrison,&nbsp;A. Tadese,&nbsp;A. Jacob,&nbsp;H. Simmons,&nbsp;E. S. Jaffe,&nbsp;M. Roschewski,&nbsp;L. M. Staudt,&nbsp;W. H. Wilson","doi":"10.1002/hon.70094_316","DOIUrl":"https://doi.org/10.1002/hon.70094_316","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Introduction:&lt;/b&gt; Targeted ViPOR therapy leads to durable remissions in R/R non-GCB DLBCL (Melani et al. &lt;i&gt;Blood.&lt;/i&gt; 2024). We hypothesized that polatuzumab may improve outcomes and conducted a Phase I/II study of ViPOR-P. Here, we present updated efficacy and new MRD data from our ongoing ViPOR-P study.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; R/R DLBCL pts with adequate organ function were eligible. Polatuzumab 1.8 mg/kg IV D2, venetoclax 800 mg PO D2–14, ibrutinib 560 mg PO D1–14, prednisone 100 mg PO D1–7, obinutuzumab 1000 mg IV D1–2, and lenalidomide 15 mg PO D1–14 were given as previously described (Melani et al. &lt;i&gt;Blood&lt;/i&gt;. 2024). ViPOR-P q21d × 6C was given without maintenance or consolidation. All pts received TLS and G-CSF ppx. Baseline CT, PET, BM, and tumor bx was performed with CT scans after C2, 4, and 6 and PET after C6. Surveillance CT was performed q3m × 1y, q4m × 1y, q6m × 1y, and q12m × 2y. MRD was assessed in plasma ctDNA using clonoSEQ at baseline, during tx, and in f/u.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; 40 DLBCL pts (15 in Ph 1 &amp; 25 in Ph 2) enrolled. Median (range) age was 55y (23–83) with 73% male. 22 (55%) pts had non-GCB DLBCL, 11 (28%) HGBCL-DH-&lt;i&gt;BCL2&lt;/i&gt;, 4 (10%) THRLBCL, 2 (5%) HGBCL-DH-&lt;i&gt;BCL6&lt;/i&gt;, and 1 (3%) GCB DLBCL. Stage III/IV disease was seen in 83% with IPI &gt; 3 in 55%. Median (range) prior tx were 2 (1–6), with prior CAR-T in 40% and 53% of pts refractory per SCHOLAR-1.&lt;/p&gt;&lt;p&gt;G3–4 heme AEs (% cycles) included thrombocytopenia (26%), neutropenia (21%), and anemia (13%), with 2 febrile neutropenia events in 145 total cycles. All grade non-heme AEs (% pts) included hypokalemia (97%), diarrhea (76%), elevated LFTs (53%), and nausea (50%). G1–2 neuropathy occurred in 26% with no G3–4 neuropathy seen. 1 uncomplicated TLS event occurred and there was no tx-related mortality. Dose reductions occurred in 32% of pts, and 2 pts prematurely stopped tx due to toxicity.&lt;/p&gt;&lt;p&gt;In 36 evaluable pts off-tx, ORR was 78% (28/36) and CR rate was 56% (20/36). By IHC, CR rate was 67% (16/24) in non-GCB and 33% (4/12) in GCB, with all GCB CRs in HGBCL-DH-&lt;i&gt;BCL2&lt;/i&gt;. By RNA-seq, CR rate was 78% (7/9) in ABC, 45% (5/11) in GCB, and 100% (1/1) in unclassified DLBCL. In refractory and post-CAR-T pts, CR rate was 40% (8/20) and 38% (6/16), respectively. In 29 MRD evaluable pts, 66% (19/29) of all pts and 100% (18/18) of PET CR pts were MRD undetectable at EOT (Figure 1A). Undetectable MRD after C1 or at EOT was associated with improved PFS. With a median f/u of 28m, 71% of CRs are ongoing with a 2y PFS and OS of 41% and 53%, respectively. 2y PFS was 49% in non-GCB and 25% in GCB by IHC (Figure 1B), and 67% in ABC and 27% in GCB by RNA-seq. In refractory and post-CAR-T pts, 2y PFS was 22% and 26%, respectively.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; ViPOR-P × 6C leads to durable undetectable MRD CRs in R/R DLBCL, especially non-GCB and ABC subtypes, further validating the curative potential of ViPOR-based treatment. Compared to ViPOR, ViPOR-P is safe without sig","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_316","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292962","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}