Introduction:Peripheral T-cell lymphoma (PTCL) is a heterogeneous and highly aggressive subtype of non-Hodgkin lymphoma. Approximately 30% of patients develop relapsed or refractory PTCL (R/R PTCL) due to disease recurrence or failure to achieve complete remission after first-line therapy. Despite therapeutic advances, the molecular and cellular mechanisms underlying treatment resistance in R/R PTCL remain unclear. Methods:Single-cell RNA sequencing and single-cell T-cell receptor sequencing were performed on seven tumor samples from six patients with R/R PTCL. These approaches were used to systematically characterize the transcriptional profiles of malignant T-cell clones and reactive T lymphocytes, define the transcriptomic landscape of R/R PTCL, and identify potential epigenetic biomarkers associated with drug response. Results:We observed significant upregulation of genes associated with cell proliferation, oncogenic signaling, and immune modulation in R/R PTCL. Within the tumor microenvironment, specific protumorigenic ligand-receptor interactions were identified, including CXCL13-CXCR5, CCL5-CCR5, and CD74-MIF interactions, which may facilitate immune evasion by malignant T cells. Longitudinal analysis of a patient who progressed following dual epigenetic therapy revealed marked downregulation of immune response-related genes, including HLA-DRA/DPA1/DRB5, CD74, C1QC, and LYZ, as well as functional reprogramming of tumor-associated macrophages. Enhanced LGALS9-HAVCR2 and CSF1-CSF1R interactions were also observed following combination treatment with chidamide and azacitidine. Discussion:This study delineates the transcriptional heterogeneity of malignant T-cell clones in R/R PTCL and suggests that this heterogeneity may contribute to resistance to epigenetic therapies. These findings provide novel insights into the molecular mechanisms underlying treatment resistance and highlight potential avenues for therapeutic intervention in R/R PTCL.

Introduction This study constructs a high-resolution multi-omics map of Diffuse Large B-Cell Lymphoma (DLBCL) by integrating single-cell, single-nucleus, and spatial transcriptomics.Methods We identified a previously unrecognized, recurrent subset of malignant B cells that unexpectedly express CD3, a protein typically found only on T cells. This unusual CD3⁺ B cell population appears to be driven by a specific genetic circuit involving five key regulatory genes: BCLAF1, CHURC1, FLI1, NFATC2, and ELF2.Result Spatial and functional analyses revealed that these cells are associated with macrophage enrichment and M2 polarization, potentially involving TGF-β signaling and contributing to an immunosuppressive tumor microenvironment. Clinically, the abundance of CD3⁺ B cells was associated with advanced disease stage, poor treatment response, and reduced survival.Conclusion Our findings support the presence of a CD3⁺ B cell subset with T cell-like features that is associated with tumor microenvironment remodeling and adverse clinical outcomes, highlighting molecular determinants like FLI1 and the TGF-β axis as potential therapeutic targets.

Primary large B-cell lymphoma of immune-privileged sites (IP-LBCL), a recently defined entity in WHO-HAEM5, includes primary diffuse large B-cell lymphoma (DLBCL) occurring in immune-privileged areas like the central nervous system (PCNS-LBCL), vitreoretinal system (PVR-LBCL), and testis (PT-LBCL) in immunocompetent patients. This study aimed to identify prognostic factors and create a predictive model for IP-LBCL. We analyzed 213 newly diagnosed IP-LBCL patients from April 2006 to April 2023. A nomogram and prognostic index, IPLBCL-PI, were developed based on elevated LDH, ECOG ≥ 2, and PCNS-LBCL subtype as independent risk factors for poorer PFS. IPLBCL-PI categorized patients into four risk groups: low, low-intermediate, intermediate-high, and high. The model effectively predicted both PFS and OS in the training cohort and was validated in two external centers. Subgroup analyses showed that IPLBCL-PI outperformed the Nottingham/Barcelona (NB) and Memorial Sloan Kettering Cancer Center (MSKCC) models in PCNS-LBCL and was comparable to the International Prognostic Index (IPI) in PT-LBCL. IPLBCL-PI is the first prognostic model for IP-LBCL, offering risk stratification and aiding clinical decision-making for this rare entity.

Background: Primary cutaneous peripheral T-cell lymphoma, not otherwise specified (pcPTCL-NOS), is a rare and aggressive form of lymphoma. Its characteristics and treatment outcomes remain poorly understood. Methods: We identified 15 patients who were diagnosed with pcPTCL-NOS between January 2014 and August 2024 at Tianjin Medical University Cancer Institute and Hospital (TMUCIH) in this retrospective study. The clinical and immunophenotypic features, treatment regimens, and outcomes of these patients were investigated. Results: All patients (4 men, 11 women; median age 54 years) presented with skin lesions, including five stage T1, four stage T2 and six stage T3 lesions. pcPTCL-NOS manifests clinically either with solitary or disseminated rapidly growing nodules/tumors and papules and, less often, ulcers. The lesion sites in patients presenting with solitary/localized tumors (stage T1 and T2) were the head and limbs, and those in patients presenting with disseminated lesions (stage T3) were the trunk, head, and limbs. The CD4/CD8 immunophenotypic characteristics were as follows: CD4+/CD8- 53.33%; CD4+/CD8+ 26.67%; CD4-/CD8- 13.33%; and CD4-/CD8+ 6.67%. One patient had a T follicular helper (TFH) phenotype. Five patients had aberrant expression of the B-cell marker CD20 by tumor cells. All patients received CHOP or CHOP-like regimens as the initial treatment, with three patients undergoing complete lesion resection before chemotherapy, seven patients receiving treatment combined with chidamide (tucidinostat), two patients receiving treatment combined with brentuximab vedotin, two patients receiving treatment combined with mitoxantrone liposomes (Lipo-Mit), three patients receiving treatment combined with radiotherapy, and two patients receiving ASCT after the first-line treatment. The OS rates at 1 year, 2 years, and 3 years were 80%, 77.8%, and 77.8%, respectively; the PFS rates were 60%, 44.4%, and 33.3%, respectively. With a median follow-up of 40 months, the median PFS was 21 months, and the median OS was not reached. Univariate analyses revealed that patients with B symptoms and the CD4-/CD8- phenotype had inferior outcomes (p < 0.05). Age, sex, tumor stage, PIT score, Ki-67 index, elevated β2-MG levels, expression of CD20 or PD1, and treatment selection were not associated with the prognosis. A trend of a survival benefit in patients with solitary (T1) tumors compared with patients with disseminated (T2, T3) tumors was observed, suggesting that it is possible to reduce the intensity of treatment in patients with T1 tumors in the future. Conclusions: pcPTCL-NOS is an aggressive but poorly characterized lymphoma that may require early and active systemic treatment. However, for patients with T1 tumors, reducing the intensity of treatment with CHOP should be appropriately considered.

Introduction Polatuzumab vedotin (pola) plus rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) demonstrated superior progression-free survival versus R-CHOP in untreated diffuse large B-cell lymphoma (DLBCL) with comparable safety. Recently, zuberitamab (Hi), a novel anti-CD20 monoclonal antibody with enhanced antibody-dependent cellular cytotoxicity, combined with CHOP, has shown non-inferior objective response rate (ORR) to R-CHOP in DLBCL and may offer higher complete response rates (CRR), especially in germinal center B-cell-like (GCB) DLBCL. Given the unmet clinical need in high-risk DLBCL and mechanistic synergy between antibody-drug conjugates (pola) and next-generation anti-CD20 agents (Hi), this study evaluated the real-world effectiveness and safety of Pola plus Hi-CHP (pola-Hi-CHP) in a Chinese cohort. Methods This retrospective study enrolled untreated adult DLBCL patients received pola-Hi-CHP at Tianjin Medical University Cancer Institute & Hospital in China between March 2024 and April 2025. Response was assessed by investigator using 2014 Lugano response criteria. Primary outcome was CRR at end of treatment (EOT), and secondary outcomes included ORR, and treatment-emergent adverse events (TEAEs). Subgroup analyses of CRR were performed based on age, Ann Arbor stage, B symptom, cell-of-origin, international prognostic index (IPI) score, expression of MYC and BCL2, and extranodal involvement. Results All patients completed the full six-cycle treatment regimen and received primary prophylaxis with long-acting granulocyte colony-stimulating factor (G-CSF). Among 72 evaluable patients (median age 63 years [range 19-83]), 54.2% were advanced stage. 16.7% patients presented with B symptoms, and 45.8% had elevated serum lactate dehydrogenase (LDH) level. 18.1% of patients had bone marrow involvement and 22.2% had more than one extranodal involvements. Most patients (76.4%) had an IPI score of 0-3, while 23.6% had an IPI score of 4-5. 54.2% of cases were non-germinal center B-cell-like (non-GCB) subtype, and 36.1% were GCB subtype. 33.3% of cases were MYC overexpression and 68.1%were BCL2 overexpression. 23.6% cases were double-expression of MYC and BCL2 proteins (DEL). Pola-Hi-CHP demonstrated a CRR of 83.3% (60/72; 95% confidence interval [CI] 69.7-89.8), with all patients attaining objective response (ORR 100%; 95% CI 95.0-100.0). Subgroup analyses demonstrated consistent CRR of pola-Hi-CHP across various subgroups, including those based on aged (<60 years: 85.2% [23/27] vs ≥60 years: 82.2% [37/45]), cell-of-origin (non-GCB: 87.2% [34/39] vs GCB: 84.6% [22/26]), and Ann Arbor stage (I/II: 81.8% [27/33] vs III/IV: 84.6% [33/39]). Patients with IPI 0-3 showed a CRR of 89.1% (49/55)compared with 64.7% (11/17) in patients with IPI 4-5, and those without B symptoms had a CRR of 85.0% (51/60) compared with 75.0% (9/12) in those with B symptoms. Bone marrow involvement was associated with a reduced CRR (76.9% [10/13] vs. 84.7% [50/59] in patients without involvement). Extranodal involvement also influenced outcomes. Among patients without extranodal involvement, the CRR was 85.7% (36/42), while it was slightly lower in those with at least one extranodal site involvement (80.0% [24/30]). Furthermore, patients with a single extranodal site involvement had a CRR of 85.7% (12/14), compared with 75.0% (12/16) in those with at least two sites involvement. Notably, patients with DEL achieved a CRR of 88.2% (15/17), while patients with MYC overexpression had a CRR of 87.5% (21/24) and patients with BCL2 overexpression had a CRR of 83.7% (41/49).The common grade ≥3 TEAEs included leukopenia (29.2%) and neutropenia (38.9%), with no new safety signals identified. Conclusions The pola-Hi-CHP regimen demonstrated encouraging effectiveness with CRR numerically exceeding historical R-CHOP and Pola-R-CHP benchmarks, particularly in non-GCB and DEL subgroups. The observed CRR reduction in high-risk IPI 4-5 patients underscores persistent therapeutic challenges in this population. Safety profiles aligned with established expectations for polatuzumab-based or zuberitamab-based regimens, with no new signals identified. These findings provide preliminary evidence supporting further evaluation of this novel combination in randomized controlled trials, particularly in subgroups defined by cell-of-origin and double-expression status.

Abstract Background Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas associated with poor survival outcomes. Relapsed or refractory (R/R) PTCLs have an even worse prognosis, with historically reported median overall survival (mOS) of less than 6 months. Current monotherapies yield only modest overall response rates (ORR) ranging from 22% to 38%, except for brentuximab vedotin in CD30-positive anaplastic large cell lymphoma (ALCL). Purinostat Mesylate (PM) is a highly selective HDAC I/IIb inhibitor. In a phase I dose-escalation study, PM achieved an encouraging ORR of 61.1% in R/R lymphomas with manageable toxicities. A phase IIa was conducted to further evaluate the efficacy and safety of PM in R/R PTCL (NCT06485219). Methods Eligible patients were adults with pathologically confirmed R/R PTCL who had received 1 to 5 prior lines of therapy, including anthracycline-based chemotherapy for PTCL and asparaginase-based therapy for NK/T-cell lymphoma (NKTCL), ECOG≤2. Patients were randomized 1:1 to receive PM at doses of 11.2 or 15.0 mg/m² on Days 1, 4, 8, and 11 of a 21-day cycle. 10-15 patients were planned to be enrolled at each group. Patients continued treatment until disease progression or unacceptable toxicity. The primary endpoint was ORR; secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Results As of July 23, 2025, 24 patients with R/R PTCL were enrolled. Baseline characteristics included a median age of 58.0 years (range: 36–76), 19 males (79.2%), and a median of 2 prior lines of therapy. Twenty patients had at least one response evaluation. After a median follow-up of 5.39 months, the ORR was 55.0% (11/20), comprising 4 complete responses (CR) and 7 partial responses (PR). Four patients at 11.2 mg/m2 (4/8) achieved an ORR of 50.0% with 1 CR and 3 PR. Seven patients at 15.0 mg/m2 (7/12) achieved ORR of 58.3% with 3 CR and 4 PR. ORRs by histology were 20% (1/5) for PTCL-NOS (CR), 100% (1/1) for NKTCL, 50.0% (5/10) for AITL, and 100% (4/4) for ALCL. Most patients can benefit from the treatment at an earlier time with a median time to response (TTR) of 2.76 months (1.28, NR), and the median duration of response (mDOR) was 6.01 months (0.66, NR). Among responders, 5 patients remain on treatment, with the longest ongoing treatment lasting 16 cycles. Median PFS was 4.24 months (2.56, 7.29) and median OS was 7.59 months (6.18, NR). The most common grade ≥3 treatment-related adverse events included neutropenia (83.3%), thrombocytopenia (75.0%), leukocytopenia (50.0%), lymphocytopenia (41.7%), anemia (20.8%), infectious pneumonia (16.7%), bacterial pneumonia (12.5%), and hypokalemia (12.5%). There was one treatment-related death due to infection. Conclusion Preliminary results from this phase IIa study indicate that PM administered in 21-day cycles demonstrates promising efficacy compared with currently available single agents, with a manageable safety profile in patients with R/R PTCL.

Little is known about the survival benefit of relmacabtagene autoleucel (relma-cel) in the current therapeutic landscape of relapsed/refractory (r/r) follicular lymphoma (FL). The current study compared the survival outcomes of Chinese FL patients administered relma-cel in RELIANCE (NCT04089215) and usual care in a retrospective, observational, large-scale real-world study (RWS). An indirect treatment comparison was carried out for 27 patients from RELIANCE and 53 patients from the RWS in China. Additionally, a direct comparison was made with the SCHOLAR-5 study, which assessed available treatment options abroad. After propensity score matching, disease status (FLIPI2 score, histological grade, relapse status, POD24) in the relma-cel group appeared to indicate more severe disease versus the usual care group. Nevertheless, median progression-free survival (PFS) was not reached (95% CI 8.97-NR) for relma-cel versus 19.98 months (95% CI 16.03-28.98) for usual care, indicating a hazard ratio (HR) of 0.40 (95% CI 0.13-1.23). Besides, a comparative analysis of RELIANCE and SCHOLAR-5, applying available treatment options abroad, revealed an HR for PFS of 0.20 (95% CI 0.07-0.58). At 24 months, 100% of patients survived after relma-cel infusion, versus 38.2% after usual care in China and 62.7% after usual care treatment in SCHOLAR-5, respectively. Relma-cel exhibits superior survival benefits versus current conventional therapies in r/r FL patients after ≥ 2 treatment lines.

Polatuzumab vedotin plus R-CHP (Pola-R-CHP) is approved as a new standard first-line therapy for diffuse large B-cell lymphoma (DLBCL) based on the POLARIX trial. However, real-world data on its efficacy and safety in unselected patients is lacking. We conducted a retrospective cohort study to evaluate Pola-R-CHP versus R-CHOP outcomes in routine clinical practice in China. This is a multi-institutional retrospective cohort study and included all consecutive patients that received at least one dose of polatuzumab vedotin up until February 2024. A total of 600 eligible patients from 6 centers were identified, 131 receiving Pola-R-CHP and 469 R-CHOP. After 1:2 propensity score matching, 128 pairs were obtained for further survival and prognosis analysis. With a median follow-up of 12.8 months, 12-month progression-free survival (PFS) was numerically higher with Pola-R-CHP versus R-CHOP (90.3% vs. 84.1%, p = 0.18). Benefits were consistently observed across molecular subgroups, especially advanced stage, ECOG >= 2, extranodal involvement >= 2 and non-GCB group. The complete response rate of the Pola-R-CHP group was higher than that of the RCHOP group (86.8% vs. 79.7%; p = 0.09), but there was no statistical difference. Safety profiles were comparable, with no new concerns. Among 128 patients treated with Pola-R-CHP, 96 underwent gene sequencing analysis: MCD (25.0%), EZB (13.5%), combined subtype (12.5%), ST2 (9.4%), and other/unclassifiable subtype (30.2%). The most common mutations (> 25% of cases) were PIM1, TP53, BCL-6, KMT2D, SOCS1, BCL-2. Genetic testing results show the correlation between genotyping, gene mutations in PIM1/TP53 and therapeutic efficacy. This large real-world study supports Pola-R-CHP as an effective frontline option for DLBCL, with sustained efficacy versus R-CHOP observed in unselected populations. While 12-month PFS failed to reach statistical significance, subgroup analyses favor Pola-R-CHP. Further research with a wider population, longer follow-up, and screening of advantageous groups are warranted.

The 2022 World Health Organization Classification of Haematolymphoid tumours classifies follicular lymphoma grades 1-2 (FL1-2) and grade 3A (FL3A) as classic follicular lymphoma (cFL) and reclassifies grade 3B (FL3B) as follicular large B-cell lymphoma (FLBL), without addressing cases of patients with concurrent FL and diffuse large B-cell lymphoma (FL/DLBCL). However, genetic information on FL histologic grading remains limited, and the latest classification lacks sufficient evidence to resolve whether these subgroups represent single or multiple distinct biological entities. This study analyzed clinical data from 831 patients, whole-exome sequencing (WES) from 149 patients, and transcriptome sequencing from 63 patients to explore differences among FL1-2, FL3A, FL3B, and FL/DLBCL. Clinical analyses revealed two distinct groups: an indolent group (FL1-2 and FL3A) with favorable prognosis and an aggressive group (FL3B and FL/DLBCL) characterized by poor prognosis. Genomics revealed that FL1-2 and FL3A share a common genetic background, whereas FL3B and FL/DLBCL lack mutations in epigenetic regulators CREBBP and KMT2D but exhibit additional copy number variations (CNVs), such as 1p36.32 losses and 3p21.1 gains, which are linked to poor prognosis. Transcriptomics revealed that with increasing histologic grade, immune-related pathway activity decreases, while the activity of metabolic and cell cycle pathways increases, which may be associated with the upregulation of MYC, IRF4, and BATF expression. Together, these findings define FL3B and FL/DLBCL as biologically and clinically distinct B-cell lymphomas, differing from traditional FL. FL1-2 and FL3A differ in their tumor microenvironments rather than genetic profiles.

Abstract Background: Patients with untreated follicular lymphoma (FL) and intermediate-high risk FLIPI scores (≥2) face poor outcomes: 5-year PFS is ~50% with standard G-CHOP plus 2-year obinutuzumab maintenance, accompanied by significant toxicity (infection, cytopenias, secondary malignancies and quality-of-life deterioration). Bruton's tyrosine kinase (BTK) inhibition is a rational therapeutic strategy, as BTK signaling drives FL pathogenesis and tumor microenvironment interactions. Zanubrutinib-a next-generation, highly selective BTK inhibitor-synergizes with anti-CD20 therapy and demonstrates clinical activity in relapsed/refractory FL. The phase II ZAP (Zanubrutinib-Adapted Protocol) trial pioneers a response-adapted de-escalation paradigm integrating zanubrutinib into frontline therapy, aiming to maximize early molecular remissions while reducing treatment burden in this vulnerable population. Methods: From April 2024 to December 2024, this phase II trial (NCT06474481) enrolled 32 untreated FL patients (FLIPI 2-5) receiving 4 cycles of zanubrutinib (160mg BID) + standard G-CHOP with mandatory pegfilgrastim prophylaxis. Response-adapted therapy post-cycle 4: patients achieving CR (Deauville 1-3 + MRD negativity) initiated abbreviated 12-month maintenance (zanubrutinib + obinutuzumab); others received 2 additional induction cycles. Minimal residual disease (MRD) was assessed via dual-modality tracking: tumor-informed ctDNA (PhasED-seq, 10⁻⁶ sensitivity) at baseline/C2/C4/C6/q6mo maintenance and ClonoSEQ® NGS (BM, 10⁻⁶). Correlative studies included baseline whole-exome sequencing, serial immune profiling (35-plex CyTOF on PBMCs), and patient-reported outcomes (EORTC QLQ-C30/LY20). Primary endpoint was CR rate after 4 cycles; secondary endpoints included MRD negativity, PFS, and safety. Results: As of July 25, 2025, all 32 enrolled patients completed at least 4 cycles of zanubrutinib-enhanced G-CHOP, demonstrating striking efficacy. The primary endpoint was surpassed with a CR rate of 84.4% (27/32; 95% CI: 68.3-93.1%) after just 4 cycles. MRD negativity, assessed through dual-modality tracking, confirmed profound molecular responses: 90.6% (29/32) achieved ctDNA clearance, while 87.5% (28/32) had bone marrow MRD eradication. Notably, 84.4% of patients (27/32) showed concordant negativity in both assays, establishing a robust biomarker-defined subgroup with exceptional outcomes (97% 12-month PFS). Early molecular responders-those achieving ctDNA negativity by cycle 2 (n=24)-universally attained CR by cycle 4, compared to only 37.5% (3/8) of delayed clearers (p<0.001), validating C2 MRD as a critical decision point for de-escalation. High-risk subgroups benefited uniformly: patients with bulky disease (>7 cm, n=14) achieved an 85.7% CR rate (12/14), while those with FLIPI 4-5 (n=11) reached 81.8% CR (9/11). Patient-reported outcomes (EORTC QLQ-C30) revealed clinically meaningful improvements, with Global Health Status scores rising from 58.2 at baseline to 83.6 post-induction (Δ25.4, p<0.001)-76% of participants rated their treatment experience as “much better” than standard regimens. The safety profile supported the de-escalation strategy. Grade 3-4 neutropenia occurred in 21.9% (7/32), with only 6.3% (2/32) developing febrile neutropenia-attributable to mandatory pegfilgrastim prophylaxis. BTK inhibitor-related adverse events were mild (grade 1-2 bruising: 5/32; atrial fibrillation: 1/32), and no treatment-related deaths occurred. Conclusion: The ZAP trial demonstrates that zanubrutinib-enhanced G-CHOP induces high CR (84.4%) and MRD negativity (>90%) rates in high-risk FL, enabling early chemotherapy de-escalation (omitting 33% of cycles) and shortened maintenance (12 months) without compromising efficacy (12-month PFS: 97%). This response-adapted, MRD-guided paradigm redefines frontline FL therapy by replacing fixed-duration treatment with a precision approach.

Diffuse large B-cell lymphoma (DLBCL) is a biologically and clinically heterogeneous malignancy. Advances in transcriptomic and genetic profiling have significantly enhanced our understanding of the disease's intrinsic pathogenesis, uncovering numerous potential therapeutic targets. However, the impact of tumor-infiltrating Regulatory T cells (Tregs) on the prognosis of DLBCL remains controversial. Here, we developed a Treg-associated gene signature by integrating single-cell and bulk transcriptome data to predict the prognosis of DLBCL patients receiving standard immunochemotherapy. In total, 227 Tregs feature genes were identified, six of which were selected for constructing a prognostic signature. DLBCL patients possessing high-risk scores had significantly poorer survival outcomes than those who possess low-risk scores in NCICCR and validation cohorts. Mutations in PIM1, MYD88, DTX1, CARD11, CD79B, ETV6, BCL6, and CDKN2A were predominantly observed in the high-risk group, whereas alterations in TNFRSF14 and DNMT3A were more frequently detected in the low-risk group. Immune infiltration analysis revealed that the high-risk group exhibited an immunosuppressive microenvironment, whereas the low-risk group showed a higher abundance of non-cellular components in the tumor microenvironment (TME). Finally, the Treg features TNFRSF25 and SELL can effectively predict long-term responses to Axicabtagene Ciloleucel (Axi-cel) treatment. In summary, our study developed a prognostic signature consisting of six Treg feature genes by integrating single-cell and bulk transcriptomics to predict clinical outcomes in DLBCL patients. The risk signature was significantly associated with immunological characteristics.

Our study aimed to assess the prognostic significance of the interim National Comprehensive Cancer Network International Prognostic Index and PET-CT-related parameters for predicting patient outcomes and achieving precise risk stratification for diffuse large B-cell lymphoma (DLBCL) patients. We retrospectively analyzed the clinicopathological and PET-CT data of 498 patients diagnosed with DLBCL across three medical centers in China. 418 patients were eligible for subsequent analysis after excluding those with incomplete data and 70% of which were randomly selected as the discovery cohort, whereas the remaining 30% constituted the validation cohort. The impact of candidate factors on survival was assessed via univariate and multivariate Cox proportional hazards models. The area under the curve AUC and C-index were calculated to assess the predictive performance of models. Univariate and multivariate Cox regression analyses identified changes in total lesion glycolysis (ΔTLG), iNCCN-IPI, interim abdominal residual disease (iARD) status, and changes in the maximum standardized uptake value (ΔSUVmax) as independent prognostic factors. Leveraging the outcomes of the multivariate analysis, we constructed the iPET-NCCN-IPI prognostic model and categorized DLBCL patients into two separate prognostic risk groups based on their computed Risk Scores (RS = 0.90×iNCCN-IPI + 1.41×ΔTLG + 0.79×ΔSUVmax + 0.83×iARD). The predictive performance of the model was validated by calculating the area under the receiver operating characteristic curve and the C-index. Notably, compared with other models, the iPET-NCCN-IPI demonstrated superior prognostic capability. In conclusion, our study indicates that the iPET-NCCN-IPI stratifies DLBCL patients into two distinct prognostic risk groups and surpasses other models in prognostic predictive ability.

Follicular lymphoma (FL) is a common B-cell lymphoma and typically affects the elderly population. It is urgently required to enhance our comprehension of disease-specific outcomes in elderly FL patients and identify a reliable predictive indicator to assess patient risk and guide treatment options for them. Therefore, we retrospectively analysed clinical data of 128 elderly patients (aged 60 years or older) with FL treated at Tianjin Medical University Cancer Institute & Hospital from 2002 to 2020. Univariate and multivariate analyses were performed to identify high risk prognostic factors, and we evaluated the predictive capacity of several prognostic scoring models by survival analysis and receiver operating characteristic (ROC) curves. Our analysis revealed that the age ≥70 was a significant independent predictor for both OS and PFS. FLIPI2 model can classify elderly FL patients into two risk groups with different prognoses, but the FLIPI and PRIMA-PI scoring systems may not be as applicable to this specific patient population. Based on the above results, we modified the FLIPI2 scoring system to set age ≥70 years as a risk factor and developed a novel prognostic index called the Age-adjusted FLIPI2 (A-FLIPI2), which effectively classified older FL patients into three distinct groups with significantly different outcomes. Among the four scoring systems evaluated, A-FLIPI2 showed the highest AUC for predicting risk of death (0.793) and disease progression (0.678). And the performance of A-FLIPI2 is validated in an external validation cohort. Thus, A-FLIPI2 is a better prognostic model for elderly FL patients. In conclusion, the newly developed prognostic index A-FLIPI2 in this study offers improved risk stratification for elderly FL patients.

e19001 Background: DLBCL comprises 38% of all non-Hodgkin lymphoma (NHL) in China. Outcomes for R/R DLBCL remain poor despite treatment (tx) advances including CAR T-cell therapy, for which access can be limited. Thus, an unmet need in China remains, especially for chemorefractory R/R DLBCL. Subcutaneous (SC) epcor is a CD3xCD20 bispecific antibody approved globally, including the US, for R/R DLBCL and follicular lymphoma (FL). Here we present first efficacy and safety data from R/R DLBCL Chinese pts treated with epcor monotherapy in the pivotal EPCORE NHL-4 (NCT5201248) trial. Methods: Pts had R/R NHL with ≥2 lines of prior systemic tx and were administered 48 mg epcor SC in 28-day cycles (C): QW, C1-3; Q2W, C4-9; Q4W, C10+ until disease progression or unacceptable toxicity. In C1, step-up dosing (day [D] 1, 0.16 mg; D8, 0.8 mg; D15, D22, 48 mg) and prophylactic corticosteroids were used to prevent cytokine release syndrome (CRS). Key endpoints included tx-emergent adverse events (TEAEs), response rates (overall response rate [ORR]/complete response rate [CRR]) and progression-free survival (PFS) by independent review committee (IRC), and duration of response (DoR/DoCR) by IRC. Results: As of June 19, 2024, 42 pts were enrolled (3 DLBCL, 2 FL in safety run-in; 37 DLBCL in dose expansion). In dose expansion, median age was 57.0 y and pts received ≥1 epcor dose; median follow-up was 18.5 mo. In dose expansion, 73% of pts had advanced disease (Ann Arbor Stage III–IV), 89% had primary refractory disease, and 65% were refractory to the last line of anti-CD20 tx. Median prior lines of tx was 3 (range, 2–7). Most pts (97%) had ≥1 Grade (G) 3/4 TEAE, most commonly lymphopenia (89%), neutropenia (57%), leukopenia (35%), and thrombocytopenia (22%). CRS was reported in 84% of pts: G1 51%, G2 32%, and no G≥3. Most CRS events occurred after the first full dose (C1D15), with median time to onset of 16 D (range, 2–29). All CRS events resolved and no pts discontinued epcor due to CRS. No pts had immune effector cell-associated neurotoxicity syndrome, and 1 pt (3%) had G3 clinical tumor lysis syndrome that resolved without dose interruption. Three fatal TEAEs were all due to progressive disease and unrelated to epcor. ORR was 65% and CRR was 38%; median DoR, DoCR, and OS were not reached (NR; Table). Conclusions: Epcor monotherapy showed favorable outcomes in Chinese pts with refractory and heavily pretreated R/R DLBCL.High ORR and CRR were achieved early and safety was manageable. CRS was low grade with predictable timing. Our results are consistent with the pivotal EPCORE NHL-1 and NHL-3 trials and support further development of epcor in China. Clinical trial information: NCT05201248 . Efficacy by IRC. Dose Expansion (n=37) ORR, % 64.9 CR 37.8 PR 27.0 Median time to response, mo (range) 1.4 (1.1–2.8) Time to CR 2.2 (1.1–5.4) Median DoR, mo (95% CI) NR (1.5–NR) DoCR NR (3.9–NR) Median PFS, mo (95% CI) 4.5 (2.7–NR) Median OS, mo (95% CI) NR (6.5–NR)

ObjectiveThis study aimed to evaluate the efficacy and safety of rituximab, methotrexate, cytarabine with or without ibrutinib in newly diagnosed primary central nervous system lymphoma (PCNSL) and explore the correlation between efficacy and genomic alterations.MethodsFrom March 2013 to October 2022, data from 88 patients with newly diagnosed PCNSL were retrospectively collected and analyzed. Fifty-nine patients received rituximab, methotrexate and cytarabine (RMA, group A), and twenty-nine patients received the same RMA combined with ibrutinib (RMA + Ibrutinib, group B).ResultsAt a median follow-up of 27.7 months, the complete response rate (CRR), overall response rate (ORR) and overall survival (OS) in group B superior to group A (41.4% versus 16.9% for CRR, P=0.013; 86.2% versus 59.3% for ORR, P=0.011; P=0.036 for OS). The ORR, progression-free survival (PFS) and OS of RMA + ibrutinib +deep lesions (group C) were better than those of RMA + deep lesions (group D) (P=0.027 for ORR, P=0.046 for PFS, P=0.004 for OS). Patients in group B had no more toxicities than those in group A and the most common adverse events in the two groups were primarily grade 1-2. Sequencing of tumor tissues from 22 patients showed that MYD88 mutations were the most frequent genetic alterations, two patients with CARD11 mutation did not respond to treatment and three patients without an MYD88 or CD79B had response after treatment.ConclusionsRMA in combination with ibrutinib regimen improved response rates and survival in newly diagnosed PCNSL with no serious adverse effects. Mutations in CARD11 gene may provide directions for patients to select targeted drugs.

Primary lymphoma of the female genital tract (PLFGT) is a rare disease. The incidence is gradually increasing each year. There have been few reports about PLFGT, and most of them have involved individual cases and small-sample retrospective analyses. The pathogenesis of PLFGT is still under exploration and may be associated with hormones, inflammation/infection, and immunodeficiency. Diffuse large B-cell lymphoma (DLBCL) is the most common pathological type. The majority of the patients presented with vaginal bleeding, abdominal pain, an abdominal mass, and other nonspecific symptoms. Lymphoma-associated B symptoms are quite rare. These patients initially visited gynecological departments, possibly leading to misdiagnosis due to nonspecific features. The treatment strategies for and prognosis of PLFGT differ substantially from those of other gynecologic malignancies. Thus, interdisciplinary cooperation among gynecologists, pathologists, and hematologists is essential.

BackgroundDiffuse large B-cell lymphoma (DLBCL) exhibits immunological heterogeneity that influences outcomes of immunochemotherapy, with CD8+ T cells playing a critical role in patient prognosis.MethodsWe integrated single-cell and bulk transcriptome data to establish a CD8⁺ T cell–associated prognostic signature. Single-cell RNA sequencing data from 29 samples (28 individuals), including DLBCL and reactive lymph nodes/tonsils, were analyzed to characterize CD8⁺ T cell heterogeneity, identify distinct subsets, and screen differentially expressed genes. Least absolute shrinkage and selection operator (LASSO) regression combined with multivariable Cox analysis was applied to bulk RNA-seq datasets to construct a prognostic model.ResultsAnalysis of 19,483 CD8⁺ T cells revealed eight transcriptionally distinct subsets, from which 48 genes were associated with clinical outcomes. Eight prognostic genes were incorporated into a CD8⁺ T cell–related signature, with higher CD69 and CD70 expression correlating with inferior survival. The signature effectively stratified patients into high- and low-risk groups that differed in cell-of-origin subtype, mutational landscape, and immune microenvironment characteristics. Moreover, the model showed potential to predict baseline response to chimeric antigen receptor T-cell (CAR-T) therapy.ConclusionThis study highlights CD8+ T cell heterogeneity in DLBCL and establishes a prognostic gene signature that informs patient survival prediction and CAR-T therapy efficacy.

Patients with relapsed/refractory follicular lymphoma (R/R FL) refractory to anti-CD20 therapy face dismal outcomes and limited options. Preclinical evidence indicates that glofitamab-a CD20xCD3 T-cell-engaging bispecific antibody-induces PD-1/PD-L1 upregulation, creating a strong rationale for synergistic PD-1 blockade. We present the first clinical translation of glofitamab combined with tislelizumab (anti-PD-1) in this high-risk population. Methods In this single-center retrospective study (Feb 2024-May 2025), 12 consecutive R/R FL patients received a fixed-duration regimen: Cycle 1: Obinutuzumab 1,000mg (Day 1, CRS prophylaxis) followed by glofitamab step-up dosing (2.5mg→10mg→30mg on Day 8/15/22). Cycles 2-12: Glofitamab 30mg + tislelizumab 200mg every 3 weeks (maximum 12 cycles). Endpoints included ORR/CR (Lugano 2014), MRD negativity (<10⁻⁵ by next-generation flow cytometry in peripheral blood/bone marrow), progression-free survival (PFS), safety (CTCAE v5.0), and tumor genomic profiling (128-gene NGS panel). Results Patients (58.3% male) had a median age of 66 years (range: 56-78) and a median of three prior treatment lines (range: 2-9); all patients are anti-CD20 refractory. As of July 25, 2025, in 12 high-risk R/R FL patients, glofitamab combined with Tislelizumab achieved an 100% overall response rate (ORR; 12/12) with 83.3% complete remission (CR; 10/12) and responses remained ongoing at a median follow-up of 10.4 months. Critically, all CR patients (10/10) achieved minimal residual disease (MRD) negativity (<10^−5 by next-generation flow cytometry) in peripheral blood and bone marrow at response assessment. Treatment was well-tolerated with only grade 1-2 cytokine release syndrome (41.7%, 5/12) and no grade ≥3 immune-related adverse events. The most common AEs (>20%) were pyrexia (41.7%, 5/12), neutropenia (33.3%, 4/12), anemia (33.3%, 4/12), and decreased appetite (25%, 3/12). The most common Grade ≥3 AEs (>10%) were neutropenia (16.7%, 2/12). Genomic profiling revealed recurrent mutations in epigenetic regulators (CREBBP 58.3%, KMT2D 50%) and TNFRSF14 (41.7%), with all CR patients harboring alterations in CREBBP and/or KMT2D. Conclusion Glofitamab plus tislelizumab demonstrated transformative clinical activity in ultra-high-risk R/R FL, achieving 100% ORR and 83.3% CR with durable MRD-negative remissions in a population uniformly refractory to anti-CD20 therapy. The regimen's exceptional safety profile (no high-grade immune toxicity) and predictive role of CREBBP/KMT2D alterations support this fixed-duration, chemotherapy-free strategy as a paradigm shift, representing the first clinical validation of synergistic PD-1 blockade with T-cell-engaging bispecifics in FL.