INTRODUCTION:The selection of an optimal maintenance agent in diffuse large B-cell lymphoma (DLBCL) continues to pose a significant clinical challenge. This study aims to evaluate the prognostic impact of maintenance therapy (MT) in DLBCL. METHODS:We conducted a retrospective analysis of data from DLBCL patients undergoing first-line MT at four hospitals in Beijing between January 2019 and August 2024. The REMoDL-B trial database was selected as the control group. RESULTS:The MT group comprised 106 cases and a median follow-up duration of 25.4 months. The rates of progression and death were 11.32% (12/106) and 1.89% (2/106), respectively. The 2-y progression-free survival (PFS) and overall survival (OS) rates were 90% and 98%, respectively. The MT group demonstrated significantly superior PFS and OS compared to the control group (p = 0.024, p = 0.008). Furthermore, multivariate analysis indicated that MT (p = 0.021, OR = 0.037, 95% CI, 0.002-0.605) was an independent prognostic factor associated with improved PFS. For patients receiving Bruton tyrosine kinase inhibitors (BTKi), the 2-y PFS and OS rates were 87.6% and 97.2%, respectively, both significantly better than those of the control group (p = 0.048, p = 0.024). Despite 43.6% of patients being at high risk for central nervous system (CNS), no CNS recurrences were observed. The PFS of the MCD subtype is better than that of the A53 subtype. CONCLUSIONS:While limited by the retrospective study, our analysis raises the hypothesis that MT may correlate with improved DLBCL outcomes. A similar trend suggesting potential benefit from BTKi maintenance was noted, meriting further investigation in controlled settings.

Primary central nervous system lymphoma (PCNSL) is a rare, aggressive malignancy presenting significant therapeutic challenges. Optimal maintenance therapy following initial remission remained debated. We conducted a multicentre, real-world study comparing BTK inhibitors (BTKi, n = 23) versus lenalidomide (n = 48) as maintenance in 71 newly diagnosed PCNSL patients in remission. With a median follow-up of 41.2 months, median overall survival (OS) and progression-free survival (PFS) remained unachieved for the total cohort. BTKi maintenance was associated with significantly superior PFS compared with lenalidomide (not achieved vs. 61.0 months; p = 0.016), with a substantially higher 6-year PFS rate (91.3

This phase 2, single-arm, multi-center study (NCT03934567) evaluates the efficacy and safety of abexinostat, a histone deacetylase inhibitor, in patients with relapsed or refractory (r/r) follicular lymphoma (FL). Eligible participants had previously received a minimum of two systemic treatment lines, such as cytotoxic agents and/or anti-CD20 monoclonal antibodies. Participants received abexinostat 80 mg oral twice daily on a schedule of seven days on and seven days off, within 28-day cycles, continuing until unacceptable toxicity or disease progression occurred. The primary endpoint was objective response rate (ORR), evaluated by an independent review committee (IRC). Secondary endpoints comprised duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Between May 2, 2019, and November 19, 2023, 90 patients were enrolled. As of October 08, 2024, with a median follow-up of 30.55 months (95% confidence interval [CI] 23.72-33.64), 17.8% (16/90) of patients were still on study treatment. The ORR was 69.5% (57/82, 95% CI 58.4-79.2), with a complete response rate of 14.6% (12/82). The DCR was 91.5% (75/82, 95% CI 83.2-96.5). Tumor size reduced in 89% (73/82) of patients. The median DoR was 13.96 months (95% CI 9.20-not reached [NR]) and the median PFS was 13.80 months (95% CI 9.69-30.26). The median OS was 47.18 months (95% CI 45.70-NR). The most common treatment-emergent adverse events were thrombocytopenia (77/90, 85.6%), neutropenia (53/90, 58.9%), and leukopenia (47/90, 52.2%). The results of this study demonstrated that abexinostat had promising efficacy and manageable safety profile, supporting abexinostat as a new treatment option for the third-line or later-line treatment of r/r FL.

6567 Background: Accurate cytogenetic characterization is critical for risk stratification in myelodysplastic syndromes (MDS). Conventional karyotyping and fluorescence in situ hybridization (FISH) are limited in resolution, target specific loci, and cannot detect copy-neutral loss of heterozygosity (CN-LOH). LeukoPrint, a CE-IVD-marked shallow whole-genome sequencing (sWGS, 1×coverage) test, enables genome-wide detection of copy number alterations (CNAs) and CN-LOH. Previously validated in acute myeloid leukemia and multiple myeloma, it improved CNA detection and prognostic accuracy. This study evaluated its ability to enhance diagnostic yield and refine prognostic precision in a large MDS cohort. Methods: Bone marrow samples from 461 MDS patients were profiled for genome-wide CNA/CN-LOH using LeukoPrint. Results were compared with conventional karyotyping and FISH to assess detection yield and concordance. The impact of additional LeukoPrint findings on Revised International Prognostic Scoring System (IPSS-R) cytogenetic risk stratification and MDS subclassification was evaluated. Results: LeukoPrint detected cytogenetic abnormalities in 63.3% of patients, comprising CNAs in 50.3%, CN-LOH in 23.9%, with 10.8% harboring both. Recurrent CNAs included del(5q) (10.0%), del(20q) (10.0%), +8 (8.9%), and del(7q) (7.8%), among others. CN-LOH frequently affected regions that overlapped common CNA loci, such as 5q (3.7%), 7q (3.7%), and 17p (0.7%). Compared with conventional cytogenetics, LeukoPrint showed 94.4% concordance (κ=0.854) with FISH for five key loci (−5/del(5q), −7/del(7q), +8, del(20q), −Y) and a higher detection rate than karyotyping (65.7% vs 39.2%). For the 11 IPSS-R defined cytogenetic abnormalities (del(3q), del(5q), del(7q), del(11q), del(12p), del(17p), del(20q), +8, +19, -7, and -Y), it identified all karyotype-detected lesions and increased detection yield by 49.4%. These newly identified abnormalities led to IPSS-R cytogenetic risk reclassification in 32.4% (33/102) of comparable cases, predominantly upgrading patients to higher-risk categories. Specifically, 26 patients were reassigned from Good to Intermediate (n = 17), Poor (n = 2), or Very Poor (n = 7); 5 from Intermediate to Poor (n = 4) or Very Poor (n = 1); and 1 from Poor to Very Poor. Furthermore, by detecting additional aberrations such as del(17p) or 17p CN-LOH, LeukoPrint enabled more accurate molecular classification, including the reclassification of one case from MDS-IB1 to MDS-biTP53. Conclusions: sWGS-based LeukoPrint substantially enhances cytogenetic detection in MDS, outperforming conventional karyotyping and FISH. By identifying additional clinically relevant cytogenetic abnormalities, it improves prognostic risk stratification and refines disease classification, supporting its integration into routine MDS cytogenetic assessment.

This multicenter, randomized, controlled study was conducted to explore the safety and efficacy of low-dose baricitinib plus danazol for ITP patients who had failed corticosteroids and at least one recommended subsequent treatment. Participants were randomly assigned to receive baricitinib plus danazol (n = 108) or danazol alone (n = 108) by a central, interactive web-based system. Patients and caregivers were not blinded to group assignment. Efficacy assessments were performed in the intention-to-treat population by investigators blinded to group assignment. The primary endpoint was 6-month durable response. Forty-nine (45.4%) patients in the combination arm and 22 (20.4%) patients in the monotherapy arm achieved 6-month durable response (P < 0.001). The safety analysis set included patients who received at least one dose of study medication (n = 108 in the combination arm and n = 105 in the monotherapy arm). Fifty-two (48.1%) patients receiving baricitinib plus danazol and 47 (44.7%) patients receiving danazol alone reported at least one adverse event. Each arm reported two patients who developed an adverse event causing study discontinuation and one patient who developed a grade 3 or more severe adverse event. Low-dose baricitinib plus danazol might be a novel option for difficult-to-treat ITP. Funding: National Key Research and Development Program of China (No. 2023YFC2507800), National Natural Science Foundation of China (No. 82230004, No. 82430006, No. 82400157), Capital Health Development and Research of Special (No. 2022-1-4082), and Beijing Natural Science Foundation (No. 7242154 and No. 7232188). ClinicalTrials.gov identifier: NCT05852847.

Background:The advent of novel therapies including chimeric antigen receptor (CAR) T cells, bispecific antibodies (BsAbs), and antibody-drug conjugates (ADCs), has markedly improved clinical outcomes for relapsed or refractory large B-cell lymphoma (R/R LBCL). However, direct comparisons of efficacy and safety among systemic treatments for R/R LBCL are lacking, complicating clinical decision-making. Methods:A systematic literature search was conducted across PubMed, Embase, and the Cochrane Library to identify eligible randomized controlled trials (RCTs). A Bayesian network meta-analysis (NMA) was performed to evaluate the systemic therapies across transplant-eligible and transplant-ineligible patients with R/R LBCL. The primary endpoint was progression-free survival (PFS), secondary endpoints included event-free survival (EFS), overall survival (OS), objective response rate (ORR) and grade ≥3 treatment-emergent adverse events (TEAEs). Results:The analysis included 14 RCTs comprising a total of 3,329 patients. Among the transplant-eligible cohort (7 evaluated regimens), CAR-T therapies maximized disease control; lisocabtagene maraleucel (liso-cel) ranked highest for PFS [hazard ratio (HR) =0.42; 95% credible intervals (CrI): 0.28-0.64] and EFS (HR =0.37, 95% CrI: 0.26-0.54), whereas axicabtagene ciloleucel (axi-cel) was associated with the highest incidence of grade ≥3 TEAEs [risk ratio (RR) =2.09; 95% CrI: 1.08-4.19]. In the transplant-ineligible cohort (9 evaluated regimens), glofitamab plus gemcitabine and oxaliplatin (Glofit-GemOx) ranked highest for PFS (HR =0.32; 95% CrI: 0.23-0.45), while polatuzumab vedotin plus bendamustine and rituximab (Pola-BR) yielded the maximum benefit for OS (HR =0.42; 95% CrI: 0.24-0.73) and ORR [odds ratio (OR) =5.21; 95% CrI: 2.01-14.3]. Both regimens were associated with higher toxicities, but remained overall manageable. Conclusions:This NMA provides a comprehensive comparison of systemic treatment strategies for R/R LBCL regarding efficacy and safety profiles.

Current biomarkers and prognostic systems lack sufficient evaluation of their predictive power on HMA efficacy for myeloid neoplasms. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to uncover the target module correlated with HMA response. Based on this module, Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to establish a predictive model with non-zero coefficients, termed the HMA-29 model. The magenta module was identified as the target module correlating with HMA response (R² = 0.37, p = 2 × 10⁻⁴). LASSO regression established the HMA-29 model, comprising the expression signatures of 29 genes, which stratified patients into responsive-like and resistant-like groups. HMA-29 risk scores significantly differed between HMA responders and non-responders and demonstrated superior predictive performance (AUC 0.9982, p < 0.0001). The predictive capability was validated across independent cohorts/disease subtypes/HMA drugs/sampling conditions. Notably, HMA-29 risk scores did not significantly differ between pre- and post-treatment samples. Moreover, Kaplan-Meier analysis demonstrated significant differences of disease-free survival (DFS) and overall survival (OS) between the HMA-29-defined groups. GSEA indicated that the G2M checkpoint, MYC targets, and E2F targets were positively associated with HMA-29 risk. We developed a novel predictive model for HMA response in myeloid neoplasms, demonstrating superior predictive and prognostic value compared to existing systems. Our findings provide insights into potential therapeutic strategies, including the integration of targeted therapies with HMA treatment.

Abstract: Comprehensive detection of copy number aberrations (CNAs) is critical for precise prognostic risk stratification in multiple myeloma (MM), yet conventional cytogenetic methods remain limited. We developed LeukoPrint, a shallow whole-genome sequencing (sWGS) assay for genome-wide CNA profiling. Using this platform, we analyzed CNA profiles of 423 patients with MM across 3 hospitals and compared LeukoPrint with karyotyping and fluorescence in situ hybridization (FISH) to evaluate its diagnostic performance and clinical utility in prognostic assessment. Compared with karyotyping, LeukoPrint demonstrated a significantly higher abnormality detection rate (75.2% vs 11.2%) and identified CNAs in 73.3% of karyotyping-negative cases. Concordance with FISH for key prognostic CNAs (amp(1q), del(1p), del(13q), del(17p)) was 94.0%. Based on these findings, we propose replacing karyotyping with LeukoPrint combined with FISH for routine diagnostics. Integrating LeukoPrint with FISH results into the Mayo Stratification for Myeloma and Risk-Adapted Therapy risk model reclassified 11.5% of standard-risk patients as high-risk, identifying candidates for intensified therapy. Furthermore, LeukoPrint genome-wide profiling revealed distinct CNA patterns between hyperdiploid and nonhyperdiploid MM, informing biological heterogeneity. LeukoPrint significantly outperforms conventional karyotyping and closely matches FISH for critical CNA markers, offering an alternative for cytogenetic profiling and prognostic risk stratification in MM.

BackgroundThe global epidemiological trends of chronic lymphocytic leukemia (CLL) provide a crucial macrolevel foundation for guiding precision medicine. However, translating broad risk factors and burden disparities into actionable clinical strategies requires a bridge to molecular pathogenesis. This study analyzes the global CLL burden to not only delineate its public health landscape but also inform the development of biomarker-based prevention and early detection frameworks.MethodsLeveraging data from the Global Burden of Disease Study 2021, we evaluated primary pre-pandemic trends in CLL incidence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2019 using estimated annual percentage change (EAPC), joinpoint regression, and decomposition analysis to identify key drivers of trends and inequalities. Predictive modeling (ARIMA) was employed to project future burden. Critically, the epidemiological insights-particularly regarding identified risk factors (e.g., smoking, high BMI) and high-burden populations-were framed as a strategic map to prioritize hypotheses for subsequent biomarker discovery research in CLL etiology and progression. We additionally analyzed three independent Gene Expression Omnibus (GEO) transcriptomic cohorts including CLL patients and nonleukemic controls. Differential expression analysis across cohorts identified 67 overlapping CLL-related genes, which underwent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Using least absolute shrinkage and selection operator (LASSO)-regularized logistic regression in a training cohort, we derived a 14-gene predictive signature and validated its discriminative performance in independent datasets.ResultsThe analysis revealed a mild decline in global age-standardized incidence but significant declines in mortality (31.3%) and DALYs (32.9%), alongside marked socioeconomic disparities. Decomposition analysis quantified the dominant role of population aging in driving DALY increases in Western Europe (+11403.53%) and epidemiological factors in Central Asia (+633.72%). Smoking and high body mass index were reaffirmed as modifiable risk factors. Projections indicate declining incidence and mortality but rising prevalence through 2040. These findings pinpoint specific demographics and risk exposures as high-priority targets for biomarker investigation and stratified screening. At the molecular level, differential expression analyses across three GEO cohorts identified 67 overlapping CLL-related genes, which were significantly enriched in immune cell differentiation, leukocyte adhesion, T/B cell receptor signaling, and cytokine/growth factor pathways. A LASSO-based model further distilled these into a 14-gene signature that effectively discriminated CLL from non-CLL samples in the training cohort and retained stable predictive performance in independent validation sets.ConclusionThis study synthesizes the global epidemiology of CLL into a framework that informs clinical and translational research. By combining global burden analysis with a complementary transcriptomic investigation, it provides epidemiological context and candidate molecular features for future biomarker-based risk stratification and early identification strategies in CLL.

Classical Hodgkin lymphoma (cHL) has excellent survival outcomes, but real-world data from large-scale cohorts in China remain limited. This multicenter study characterized the clinical profile of a large Chinese cHL cohort to evaluate the efficacy of BV-containing regimens and investigate the prognostic value of clinical, nutritional, and biological markers, including peripheral monocyte percentage (M

Acute myeloid leukemia (AML) exhibits substantial genetic heterogeneity in elderly patients. Although validated genomic alterations have improved precision prognostication, incomplete integration of genetic profiles, particularly the underutilization of copy number alterations (CNAs) and copy-neutral loss of heterozygosity (CN-LOH), contributes to prognostic uncertainty in elderly patients with nucleophosmin 1 (NPM1)-mutated AML. To address this gap, the present exploratory single-center study evaluated 61 elderly patients with NPM1-mutated AML. Shallow whole-genome sequencing was used to detect CNAs and CN-LOH, and targeted next-generation sequencing was performed to assess mutations in myeloid-associated genes. Genomic data were integrated with clinical and laboratory parameters to evaluate their prognostic significance. NPM1 subtype A was the predominant variant, and most patients harbored 4 or 5 concurrent somatic mutations, frequently involving fms-related receptor tyrosine kinase 3 (FLT3), DNA methyltransferase 3 (DNMT3A), tet methylcytosine dioxygenase 2 (TET2), and isocitrate dehydrogenase 2 (IDH2). Overall, 65.57% of patients harbored CNAs and/or CN-LOH events, with recurrent genomic aberrations including dup(4)(q11q35) in 4 cases. No significant differences in clinical parameters, complete remission rates or overall survival (OS) were observed between CNA/CN-LOH-positive and -negative groups. However, univariate survival analysis demonstrated that the OS of patients with ≥5 total mutations or ≥3 CNA/CN-LOH events was significantly shorter compared with that of other patients. Integrative analysis revealed a trend toward shorter OS in patients with FLT3 internal tandem duplication-positive AML and ≥2 CNA/CN-LOH events, and longer OS in patients with IDH2-mutated AML without CNA/CN-LOH. Multivariate Cox regression analysis tentatively identified ≥3 CNA/CN-LOH events and ≥5 total mutations as potential independent predictors of a poor prognosis. These findings provide preliminary evidence that integrating CNA/CN-LOH burden with mutational profiles may improve risk stratification in elderly patients with NPM1-mutated AML. However, given the small sample size, single-center design and lack of external validation, larger multi-center studies are warranted to assess the robustness of these findings.

Abstract Renal impairment (RI) is a common complication of multiple myeloma (MM), accounting for ~40% of newly diagnosed MM (NDMM), which associated with higher mortality, increased hospitalization, and poorer prognosis. Rapid and effective intervention to reverse renal dysfunction is critical for the management of these patients. In our previous study, the triplet combination of pomalidomide with bortezomib and dexamethasone (PVD) showed a renal response rate of 78.8% in patients with clearance of creatinine (CrCL)≤40ml/min. However, 21.2% of patients did not respond to the regimen. Selinexor is an oral selective inhibitor of nuclear export compound, with no contraindications based on renal dysfunction. Here we reported efficacy and safety of SPVD (Selinexor, pomalidomide, bortezomib, dexamethasone) as first-line therapy in NDMM with CrCL≤40ml/min. Methods This was a prospective, multicenter, phase 2 study (ChiCTR2200064695) in NDMM with RI. Patients with myeloma-defined RI [CrCL by MDRD ≤40ml/min] were enrolled. Patients received SPVD (Cycles 1-2: Selinexor 40mg on days 1,8,15, pomalidomide 4mg on days1-14, bortezomib 1.3mg/m2 on days 1,4,8,11, and dexamethasone 20mg on day of and after bortezomib, 21days/cycle; Cycles 3-9: Bortezomib 1.3mg/m2 weekly, the other drugs was given as before, 28 days/cycle). ASCT was administered after 3-6 SPVD cycles for transplant-eligible patients. Primary endpoint was the renal ORR at 3 months. Secondary endpoints included major renal response (≥ partial response) at 3 months, hematological ORR, survival and safety profile. Results Between Oct 28, 2022, and May 7, 2025, 66 patients were enrolled across 20 centers with a median age of 62.5 years (range: 44-80). The proportion of R-ISS III was 37.9%. Median serum creatine and CrCl were 357.5 μmol/L [interquartile range (IQR): 204.4-584.3] and 14.5 mL/min (IQR: 8.5-26.6), respectively. Ten (15.15%) patients requiring dialysis at diagnosis and 5 (50%) of whom were dialysis-independent after induction therapy. Nineteen (28.8%) patients had high-risk cytogenetic abnormalities [t (4;14), t (14;16), or del(17p)]. Patients with paraskeletal plasmacytomas and peripheral blood plasma cell accounted for 7 (10.6%) and 7(10.6%), respectively. At the data cut-off date, 63 enrolled patients who received ≥1 treatment cycle and documented response evaluation was defined as the IIT population. The median follow-up time was 16.6 (IQR: 12.3-24.9) months. The median SVPD cycles were 5 (IQR: 4-8) cycles and 55 patients completed at least 3 cycles treatment. Twenty-one (31.8%) patients received first-line ASCT. The renal ORR at 3 months was 87.3%, including 39.7% renal CR, 12.7% renal PR and 34.9% renal MR. Best renal response was 88.9% (41.3% CR and 15.9% PR). The ORR of the hematological response was 93.6% (61.9% CR or better, 20.6%VGPR and 19.3% PR). For 55 patients who received ≥3 cycles SVPD, the renal ORR at 3 months was 89.5% (42.1% CR, 14% PR) and the best renal ORR was 91.2% (43.9% CR and 17.5% PR). The ORR of hematological response was 96.8%. The most common treatment emergent adverse events (TEAEs) (incidence >10%) were myelosuppression (63.6%), infection (57.6%), nausea (28.8%), peripheral neuropathy (25.8%), fatigue (19.7%)，hypokalemia (13.6%), hyponatremia (13.6%), vomiting (12.1%), constipation (12.1%). Grade ≥3 toxicity included myelosuppression (33.3%), infection (31.8%). It should be noted that 4 patients experienced hepatic failure during 1st cycle, and one patient died. Dose reduction or interruption of pomalidomide occurred in 19 (28.8%) patients due to myelosuppression and infection and 22 (33.3%) patients had dose reduction of Selinexor due to infection or vomiting, which occurred mainly during the early cycles. Seven patients adjusted their regimen for adverse TEAEs: 1 for bone marrow suppression, diarrhea and infection; 1 for heart failure; 1 for erythroderma; 1 for severe rash; 1 for liver failure and 2 for severe gastrointestinal events. The median PFS and OS were not reached. There were 13 patients who experienced disease progression. Three patients had died: one due to liver failure and severe infection; one due to severe infection; and one with the cause of death being unclear. Conclusion The treatment of SVPD has demonstrated a robust renal response rate and hematological response rate, with acceptable safety. Given the complexity of this population of patients, supportive care needs to be strengthened in the early stages of treatment.

BACKGROUND AND AIMS:Mantle cell lymphoma (MCL), an uncommon lymphoma subtype, is clinically characterized by its heterogenous behavior. Established prediction system including several clinical and biological parameters can help in determining the aggressiveness of MCL in younger patients. However, there are limited parameters on predicting the clinical outcome of older patients. The present study was performed to identify the prognostic factors and optimal treatment modalities in older Chinese MCL patients. METHODS:Patients (age ≥ 65 yrs) with MCL from 19 comprehensive hospitals in China were included. Clinical characteristics, therapeutic strategies, progression-free survival (PFS) and overall survival (OS) time of these patients were collected. RESULTS:Totally, 259 eligible patients were enrolled. The median age of patients was 69 years (range, 65-88). The median of PFS and OS were 29 months (95%CI: 26-37) and 76 months (95%CI: 61-96) months, respectively. Multivariate regression analysis determined that ECOG score ≥ 2, high MIPI score and absence of maintenance treatment were independently associated with poorer PFS of MCL patients; while ECOG score ≥ 2 and absence of maintenance treatment were independently correlated with a poorer OS. Patients with MCL who received BTKi-containing regimens or maintenance therapy showed significantly longer PFS and OS than those who did not receive these therapies. Maintenance treatment can improve the survival rate of older patients with MCL regardless of TP53 status. CONCLUSIONS:ECOG ≥ 2, high MIPI score, and absence of maintenance therapy were associated with poorer survival outcomes for older Chinese MCL patients. Maintenance therapy and BTKi-containing regimens have been shown to increase the survival rate of older Chinese MCL patients.

Introduction Treating acute myeloid leukemia (AML), a diverse group of hematological cancers affecting bone marrow and blood, remains difficult, with a five-year survival rate of about 30%. Although screening for genetic mutations and fusion genes has become essential in AML diagnosis and risk stratification, the clinical significance of copy number aberrations (CNAs) remains poorly understood. To this end, we conducted a multicenter prospective clinical trial (ChiCTR2300077695) to characterize the genomic landscape of CNAs using shallow whole-genome sequencing (sWGS), termed LeukoPrint, in AML. Interim results from the first 205 patients (pts) are reported here. Methods In this prospective multicenter clinical trial, we aim to enroll 600 newly diagnosed AML pts (excluding APL) across 13 participating hospitals in China. Bone marrow samples were collected and underwent CNA profiling via LeukoPrint (1× sWGS) at three stages: pretreatment, post-induction, and relapse. CNAs only those greater than 5 Mbp were analyzed. Conventional karyotyping analysis was performed in parallel for this cohort, and its diagnostic performance was compared with LeukoPrint. European Leukemia Net (ELN)-defined CNAs were used for risk stratification, consistent with standard cytogenetic analysis protocols. The trial received approval from the Ethics Committees of all participating hospitals, and all pts provided informed consent. By April 9, 2025, 205 pts were enrolled in this study, with 136 in the younger group (aged 18–59) and 69 in the older group (aged ≥60). All pts underwent CNA profiling using LeukoPrint at least twice, at pretreatment and post-induction phases. Results Using LeukoPrint, we detected 193 CNAs in 87 pts (42.4% of the cohort). No notable difference in detection rates was observed between younger and older groups (41.9% vs. 43.5%). CNAs were frequently identified in chromosomes 7, 8, 11, and Y (each with >5% prevalence), with the most common recurrent CNAs occurring at 8q24.21 (13% prevalence), the locus containing the MYC oncogene. Recurrent deletions were predominantly observed in 5q31.3 and 7q36.1, the genomic regions harboring the oncogenes ACSL6, CD74, and EZH2. LeukoPrint outperformed karyotyping in CNA detection (42.4% vs. 27.3%), enhancing results for 51 pts (24.9% of the cohort). Notably, 38 pts, initially classified with normal karyotypes or failed karyotyping, were reclassified as carrying CNAs. Applying the 2022 ELN criteria, three pts initially classified as low- or intermediate-risk based on genetic mutations, fusions, and karyotypes were reclassified as high-risk following LeukoPrint analysis in place of karyotyping. Clinical follow-up in two cases confirmed poor outcomes in one, supporting LeukoPrint's prognostic value. LeukoPrint demonstrates strong potential for prognostic prediction by monitoring dynamic change of molecular response in 115 pts. A significantly higher proportion of pts with post-induction CNAs were identified as non-responders than those without CNAs (6 vs. 3). Similarly, the proportion of pts without detectable post-induction CNAs was 95.5% in complete remission (CR, n=22), 83.3% in CR with partial hematologic recovery (CRh, n=6), 71.4% in CR with incomplete hematologic recovery (CRi, n=7), 0% in partial remission (PR, n=3), and 0% in non-responders (NR, n=3). Copy-neutral loss of heterozygosity (CN-LOH) occurs when one allele is lost and the remaining allele is duplicated, resulting in no net change in copy number. This genomic alteration, such as TP53 CN-LOH, can have significant clinical impact but is undetectable by traditional karyotyping or fluorescence in situ hybridization (FISH). LeukoPrint identified CN-LOH in 43 (20.9%) of 205 pts in this cohort. Notably, CN-LOH was detected in 25 out of 114 pts without detectable CNAs, revealing that LeukoPrint provides additional insights into chromosomal aberrations in 12% (25/205) of pts. Combined with 24.9% from standard LeukoPrint analysis, LeukoPrint enhanced CNA detection in at least 36.9% of pts. Conclusions LeukoPrint outperforms traditional karyotyping in detecting CNAs, improving data accuracy in over one-third of pts in this cohort. It enables dynamic monitoring of treatment response and disease progression, demonstrating strong correlation with clinical outcomes. These findings suggest that LeukoPrint holds significant promise as a complementary or alternative tool for conventional cytogenetic methods in AML.

Introduction Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive B-cell lymphoma. Due to the use of Rituximab, the prognosis for DLBCL has significantly improved. However, in patients with intermediate-high risk International Prognostic Index (IPI) scores (i.e., IPI ≥ 3) —a widely accepted tool for risk stratification—are prone to early relapse or disease progression, resulting in poor long-term outcomes. The therapeutic value of autologous hematopoietic stem cell transplantation (ASCT) as consolidation therapy compared to chemotherapy alone remains controversial in younger patients with high-risk DLBCL who achieve first-line remission. Aim We conducted a retrospective study to evaluate the prognostic impact of first-line ASCT versus chemotherapy alone in newly diagnosed DLBCL patients with high-risk IPI scores (≥3). Propensity score matching(PSM) was employed to balance baseline characteristics between treatment groups. Methods A retrospective analysis was conducted on newly diagnosed DLBCL patients with IPI scores ≥3 treated at Beijing 6 Medical Center between March 2014 and March 2023. Among 194 eligible patients, 104 received ASCT following first-line remission induction (transplant group), while 90 were treated with chemotherapy alone or combined with radiotherapy (non-transplant group). To minimize baseline imbalances, a 1:1 PSM was performed based on age. Results Among the 194 patients, 102 were male patients and 92 were female, yielding a male-to-female ratio of 1.11:1. The median age was 53（22-69）years. Among these patients, 116 patients had an IPI score of 3, while 78 had scores of 4-5. A total of 51 pairs of DLBCL patients were successfully matched for data analysis, and the baseline characteristics of the two groups well balanced consistent after matching. After PSM the 1-,3-,and 5-year progression-free survival(PFS) rates for the transplant group and non-transplant group were 95.7%、86.8%、80.2% vs 77.8%、68.0%、60.6%, respectively. The Log-rank test showed a statistically significant difference in the overall PFS between the two groups (P<0.05). The 1-,3-,and 5-year overall survival(OS)rates for the transplant group and non-transplant group were 97.8%、91.0%、84.5% vs 98.0%、77.6%、71.3%, respectively. The Log-rank test showed no statistically significant difference in the overall OS between the two groups (P>0.05) Based on 194 patients, univariate analysis identified auto-HSCT, old age, high-risk IPI score, and elevated LDH as significant predictors of PFS (P<0.05), with auto-HSCT acting as a protective factor. Conversely, old age, high-risk IPI, and elevated LDH were associated with prognostic factors. For OS, auto-HSCT, old age, IPI score 5, and elevated LDH showed significant associations (P<0.05), where auto-HSCT remained protective. After excluding variables with >30% missing data, variables with P<0.2 in univariate analysis were included in multivariate modeling. Auto-HSCT retained its independent protective effect on PFS (P<0.05), while elevated LDH remained an independent adverse prognostic indicator (P<0.05). Multivariate analysis confirmed age and elevated LDH as the sole independent predictors of OS (P<0.05). Post-PSM subgroup analysis demonstrated that auto-HSCT significantly improved PFS across all patient subgroups. Notably, patients with IPI score 3(HR = 0.12, 95% CI: 0.01–0.92, P = 0.041), non-GCB subtype(HR = 0.31, 95% CI: 0.11–0.89, P = 0.029), or elevated LDH(HR = 0.36, 95% CI: 0.14–0.95, P = 0.039) exhibited markedly enhanced PFS benefits from auto-HSCT compared to the non-transplant cohort. Trends toward improved PFS were observed in patients with CD5 positivity(HR = 0.18, 95% CI: 0.02–1.33, P = 0.093), double-expression(HR = 0.34, 95% CI: 0.09–1.27, P = 0.107), bone marrow involvement(HR = 0.32, 95% CI: 0.10–1.06, P = 0.063), or ≥1 extra-nodal sites(HR = 0.43, 95% CI: 0.17–1.07, P = 0.070). Additionally, auto-HSCT demonstrated a trend toward improved OS in patients with IPI score 3(HR = 0.16, 95% CI: 0.02–1.28, P = 0.084). Conclusion Thus, ASCT represents a promising consolidation strategy that significantly improves PFS in specific subgroups of DLBCL patients with intermediate-high or high risk. Its potential benefits in OS deserve further validation.

Background:Characteristic genetic events underpin acute myeloid leukemia (AML) heterogeneity and enable precise risk stratification. However, prognostic assessment remains ambiguous in many patients due to inadequate integration of specific genetic information. Materials and Methods:Eighty NPM1-mutated AML patients were enrolled. Copy number alterations (CNAs) were detected via shallow whole-genome sequencing (sWGS), and concurrent mutations via targeted deep sequencing of myeloid malignancy-associated genes. Clinical and laboratory parameters were integrated with genomic data for statistical analysis, with the aim of assessing the potential clinical significance of CNA profiles in prognostic stratification. Results:NPM1 mutation subtypes A, B, and D were the most prevalent, with all patients harboring at least two concurrent mutations (4-5 mutations being the most frequent), and these mutations commonly co-occurred with those in FLT3, DNMT3A, TET2, IDH2, and NRAS. Forty-one samples (51%) exhibited CNAs across diverse genomic regions, with dup(18)(p11.23) identified as the most recurrent locus. No significant differences in FAB classification, hematologic parameters, demographic characteristics (gender, age), co-mutation profiles, complete remission (CR) rates, or survival outcomes were observed between the CNA-positive and CNA-negative groups. Univariate survival analysis revealed patients with ≥2 CNAs, or FLT3-internal tandem duplication (FLT3-ITD) had significantly shorter overall survival (OS). Notably, integrative analysis of CNAs with mutational profiles showed that patients harboring both FLT3-ITD and ≥2 CNAs had the poorest OS, followed by those with FLT3-ITD and <2 CNAs, and multivariate Cox regression analysis suggests a potential association between ≥3 CNAs and adverse outcomes; however, given the limited sample size of cases with high CNA burden, this result should be interpreted with caution. Conclusion:This exploratory study suggests that combining CNAs and gene mutation profiles may potentially improve the existing prognostic evaluation system for NPM1-mutated AML patients. Confirmation of these results requires additional validation in larger prospective cohorts.

Abstract Background The combination of venetoclax with azacitidine (VEN-AZA) has been widely utilized to treat newly diagnosed patients with acute myeloid leukemia (AML) who are elderly or ineligible for intensive chemotherapy (IC). In certain patients who were unfit at diagnosis, IC might become tolerable as their performance status improves after achieving complete remission (CR) or CR with incomplete hematologic recovery (CRi). However, the clinical benefit of switching to intensive chemotherapy for consolidation remains undefined. In this retrospective study, we compared outcomes in AML patients who either switched to intensive consolidation or were maintained on VEN-AZA therapy. Methods Patients aged 55–74 years with AML from 14 Chinese centers were included if they achieved CR/CRi after 1–2 cycles of VEN-AZA therapy and subsequently became eligible for IC consolidation due to improvement of performance status (ECOG PS < 2). Patients chose to either switch to IC consolidation or continue on VEN-AZA therapy based on personal preference. Cumulative incidence of relapse (CIR) was estimated with Fine-Gray test with non-relapse mortality (NRM) being the competing risk. Relapse-free survival (RFS) and survival were estimated with the log-rank test. Fine-Gray proportional hazards models and Cox regression models were used to identify prognostic factors. Propensity score matching was performed to compare the outcome switching to IC consolidation and continuous VEN-AZA therapy. Results 214 patients were included in this study. 98 (46%) patients were male. Median age was 66 years (interquartile range [IQR], 62‒70 years). According to the ELN 2022 or 2024 recommendation, 62 (29%), 57 (27%), and 95 (44%) patients or 138 (65%), 63 (29%), and 13 (6%) patients were in favorable, intermediate and adverse risk, respectively. 57 patients switched to IC consolidation (IC cohort) for 2‒3 cycles—15 receiving modified “3+7” regimens and 42 receiving intermediate- or high-dose cytarabine— followed by VEN-AZA maintenance, while 157 patients received continuous VEN-AZA therapy (VEN-AZA cohort). Compared with the VEN-AZA cohort, the IC cohort were younger (median age, 63 versus 67 years, P< 0.001), more frequently classified as ELN 2022 low-risk (40% versus 25%, P= 0.03), and had comparable rate of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in CR1 (12% versus 11%, P = 0.77). With a median follow-up of 15 months (IQR, 9‒24 months), there were no differences in 2-year CIR (48% [29%–66%] versus 43% [33%–53%], P =0.93), cumulative incidence of NRM (2% [0%–7%] versus 6% [2%–11%], P =0.28), RFS (53% [34%–71%] versus 51% [41%–61%], P =0.58) and survival (83% [69%–97%] versus 80% [72%–88%], P =0.61) between the IC cohort and the VEN-AZA cohort. Multivariate analysis showed that whether switching to IC consolidation or not was not associated with CIR, RFS or survival. To balance baseline characteristics, initial treatment response to VEN-AZA induction and receiving allo-HSCT or not, PSM analyses were performed at a 1:2 ratio between the IC and VEN-AZA cohorts. In the PSM analysis, 55 patients in the IC cohort and 91 patients in the VEN-AZA cohort were included. There were no significant differences in 2-year CIR and cumulative incidence of NRM and 2-year probabilities of RFS and survival between the 2 cohorts. Further stratified analyses by ELN 2022 or 2024 risk classification were conducted in the PSM population. In patients with ELN 2022 intermediate-risk, IC cohort (n = 12) had a higher 2-year CIR (78% [31%–100%] versus 24% [5%–43%], P =0.06) than the VEN-AZA cohort (n= 28). In patients with ELN 2024 intermediate-risk, IC cohort (n = 18) had a higher 2-year CIR (59% [26%–91%] versus 17% [1%–33%], P =0.02) and lower 2-year RFS rate (33% [2%–65%] versus 77% [58%–96%], P =0.02) than the VEN-AZA cohort (n = 33). However, there were no difference in outcomes between the patients classified as ELN 2022 or 2024 favorable- or adverse risk. These findings remained consistent in sensitivity analyses with censoring at the time of allo-HSCT. Conclusion Our study suggests that elderly AML patients who achieved CR/CRi after VEN-AZA induction therapy derive no benefit from switching to IC consolidation. IC consolidation even appeared to be associated with a higher relapse rate in patients classified as intermediate-risk by ELN 2022 or 2024. These findings warrant validation through prospective studies.

Introduction Current first-line R-CHOP therapy achieves a cure in only 50–70% of diffuse large B-cell lymphoma (DLBCL) patients, with 20–30% relapsing after achieving complete remission. Prolonging progression-free survival (PFS) remains a key clinical challenge. Rituximab maintenance shows limited efficacy in R-CHOP-treated patients, and lenalidomide improves PFS only in elderly populations without enhancing overall survival (OS). The role of novel agents such as bruton's tyrosine kinase inhibitors (BTKi) in maintenance therapy remains underexplored. This study aimed to assess the prognostic impact of upfront maintenance therapy in patients with DLBCL. Methods We retrospectively analyzed data from DLBCL patients receiving upfront maintenance therapy (MT) across four hospitals in Beijing (Beijing Tongren Hospital, China-Japan Friendship Hospital, Beijing Tsinghua Changgung Hospital, and Beijing Luhe Hospital) between January 2019 and August 2024, with follow-up through May 2025. Patients received rituximab, lenalidomide, or BTKi for up to two years as maintenance therapy after 6-8 cycles of R-CHOP±X (X mainly indicated BTKi or lenalidomide) treatment. The patients who had not received maintenance treatment in the publicly available REMoDL-B trial database were selected as the control group. The propensity score matching (PSM) method was used to match the two groups. The analysis focused on clinical characteristics, PFS, OS, and prognostic factors. Results There were 106 cases in the MT group. The median age was 69 years. The median follow-up time was 25.4 months. 2-year PFS and 2-year OS rates were 90% and 98%, respectively. In the high-risk group of IPI (IPI score ≥3), 2-year PFS rate was 87.0%. Multivariate analysis confirmed immune-privileged site involvement (P=0.013), Ki-67≥85% (P=0.025), and duration of maintenance (DOM) <12 months (P=0.012) as independent risk factors for PFS. There was no significant difference in PFS between patients achieving CR versus PR at the end of induction therapy. After PSM analysis, the baseline data of the MT group was balanced with the control group. The PFS and OS of the MT group were significantly better than those of the control group (P=0.024, P=0.008). Multivariate analysis revealed that MT (P=0.019) was independent risk factor for PFS. The MT regimens mainly included BTKi (73.6%), rituximab (24.5%), and lenalidomide (1.9%). For patients receiving BTKi, the 2-year PFS and 2-year OS rates were 87.6% and 97.2%, respectively. The PFS and OS were significantly better than those of the control group (P=0.048, P=0.024). 43.6% patients had high central nervous system (CNS)- IPI risk, yet no CNS recurrences occurred. There is no statistical difference between the two types of covalent BTKi (zanubrutinib or orelabrutinib ). MCD/A53 subtypes showed worse prognosis. These two groups of patients predominantly received BTKi, with the A53 subtype showing a shorter PFS. Conclusions In the era of novel agents, upfront maintenance therapy remains a promising strategy for improving outcomes in DLBCL. We recommend more proactive consideration of maintenance therapy for high-risk DLBCL patients and for those achieving only PR, with a recommended duration of at least one year. BTKi maintenance may be a suitable option for the MCD molecular subtype. Future prospective studies in larger cohorts are warranted to evaluate a broader range of maintenance strategies. Keywords diffuse large B-cell lymphoma, maintenance therapy, survival

5508 Background: Immunotherapy combined with chemotherapy has demonstrated efficacy in treating endometrial cancer (EC), with greater benefit in mismatch repair (MMR)–deficient (dMMR) tumors compared to MMR-proficient (pMMR) disease. Adding an anti-angiogenic inhibitor could potentially enhance treatment outcomes, particularly in patients with pMMR tumors. Benmelstobart (BMSB, TQB2450) is a humanized monoclonal antibody against PD-L1 and Anlotinib (ALTN) is an anti-angiogenic oral multi-target tyrosine kinase inhibitor. Here, we report the results of a randomized, open-label, phase 2 trial comparing BMSB plus carboplatin/paclitaxel ± ALTN followed by maintenance BMSB ± ALTN as first-line treatment for advanced or recurrent EC patients. Methods: Eligible patients with primary advanced stage III/IV or recurrent EC, who had not received first-line systemic anticancer therapy, were randomized in a 1:1 ratio to receive either BMSB 1200mg, Carboplatin (CBP, AUC=5 mg/ml.min) and Paclitaxel (PTX, 175mg/m 2 ) every 3 weeks for 6-8 cycles plus ALTN 8mg orally once daily (2-week on/1-week off), followed by maintenance BMSB 1200mg every 3 weeks and ALTN 10mg once daily (2-week on/1-week off) (BMSB + ALTN arm); or BMSB 1200mg, CBP (AUC=5 mg/ml.min) and PTX 175mg/m 2 every 3 weeks for 6-8 cycles followed by maintenance BMSB 1200mg every 3 weeks (BMSB arm). Stratification factors included MMR status (dMMR or pMMR). The primary endpoint was objective response rate (ORR) as assessed by investigator according to RECIST 1.1. Results: As of November 1, 2024, a total of 71 patients were enrolled: 38 in the BMSB + ALTN arm, and 33 in the BMSB arm. The median duration of follow-up was 16.2 mo vs. 14.2 mo in the two arms respectively. The ORR was 86.1% (95% CI: 70.5-95.3) in the BMSB + ALTN arm and 80.6% (95% CI: 62.5-92.5) in the BMSB arm. A significant PFS benefit was observed in the BMSB + ALTN arm (HR 0.38 [95% CI 0.18-0.81]; median not reached (NR) vs. 8.41 mo) compared to the BMSB arm. The median overall survival (OS) was not reached in either arm (HR=0.29 [95% CI: 0.07-1.16]). PFS benefit was also observed in subgroups with pMMR tumors (HR 0.35 [95% CI 0.15-0.79]). The incidence of Grade ≥3 TEAEs was similar between the two arms (81.58% vs 75.76%). The most frequent Grade ≥3 TEAEs(≥20%) were decreased white blood cell count (52.63% vs 60.61%), thrombocytopenia (28.9% vs 27.2%) and anemia (26.3% vs 27.7%). Conclusions: Benmelstobart combined with carboplatin/paclitaxel and anlotinib, followed by maintenance benmelstobart and anlotinib, demonstrated clinically meaningful ORR and PFS benefits in patients with previously untreated advanced or recurrent EC. The regimen was particularly helpful in improving outcomes for patients with pMMR tumors, potentially providing a new treatment option. Clinical trial information: NCT05481645 .