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.

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.

Introduction: Autologous CD19-targeted chimeric antigen receptor (CAR)-T cell therapies have demonstrated clinical benefit for patients with R/R B-NHL; however, many patients are unable to receive these potentially life-saving therapies due to aggressive disease progression, manufacturing constraints, or limited access. A bispecific CAR-T targeting CD19 and CD20 may enhance efficacy by overcoming heterogeneous antigen expression and CD19-negative relapse. LUCAR-G39D is a first-in-class allogeneic γδ CAR-T cell therapy targeting both CD19 and CD20. (NCT06395870) Methods: This ongoing multicenter phase I clinical trial evaluates the safety and preliminary efficacy of LUCAR-G39D in adults with R/R B-NHL. Key eligibility criteria include presence of measurable lesions, expression of CD19 and/or CD20 on tumor cells, and ≥ 2 (or refractory to 1) prior lines of systemic therapy. All patients received moderate conditioning therapy with fludarabine (30mg/m2) and cyclophosphamide (500mg/m2) per day for 3-4 days followed by a single infusion of LUCAR-G39D at dose level 1 (DL1):30×106, DL2:100×106, DL3:200×106, or DL4:400×106CAR-T cells. Accelerated titration (DL1 only) followed by BOIN dose escalation was adopted. Patients who completed the 30-day DLT period were considered DLT evaluable. Treatment-emergent adverse events were graded by CTCAE v5.0; immune effector cell-associated neurologic syndrome and cytokine release syndrome (CRS) were assessed per ASTCT criteria. Objective response rates (ORR) were evaluated per Lugano 2014 criteria. CAR-T cell pharmacokinetics (PK) were assessed by qPCR. Results: As of 29 April 2025, 12 patients were dosed; 10 patients completed at least 30 days follow up or at least 1 efficacy evaluation, 10 were efficacy evaluable and 9 DLT evaluable (1 withdrawal due to PD). Of these 10 patients, the median age was 58 years (range 19-70) and 5(50%) were male. Six (60%) patients had diffuse large B-cell lymphoma, 1(10%) patient had primary mediastinal large B-cell lymphoma, and 3 (30%) had follicular lymphoma. At baseline, 10(100%) patients were CD20(+) and 6(60%) patients were CD19(+); CD19 status was unavailable for the remaining 4(40%) due to insufficient material. Four (40%) patients were IPI≥3, 3(30%) patients were triple-hit lymphoma, the median tumor burden was 1188(531-6431) mm2, and 7(70%) had stage III/IV disease. The median number of prior therapies was 3 (range 1-6). One, 4, 3, and 2 patients received DL1, DL2, DL3, or DL4, respectively. One patient at DL2 was re-dosed with the same dose level. LUCAR-G39D was well tolerated without DLT, neurotoxicity, or GvHD. CRS occurred in 4/10 (40%) patients: 2(20%) Grade 1, 1(10%) Grade 2, and 1(10%) Grade 3, with median duration 5 days (range, 3-7). Infections occurred in 5/10(50%) patients including 1(10%) Grade 1, 3(30%) Grade 2, and 1(10%) Grade 3. Of the infections, there was only 1 Grade 3 event (pneumonia); it was also the only serious adverse event and resolved post-treatment. The most common Grade 3 or Grade 4 adverse events (incidence ≥20%) included decreased neutrophil count (100%), decreased lymphocyte count (100%), decreased white blood cell (100%), and decreased platelet count (20%). No fetal adverse events occurred. PK expansion was detected in 80% (8/10) of patients for all dose levels (100% [2/2] at DL4). The median Cmax was 1999 copies/μg gDNA (range 59-164768), with a median Tmax of 5.5 days. ORR was 70% (7/10), and the complete response rate was 30%(3/10) for all patients (3 patients had deepening efficacy from Days 30-90). Both patients at DL4 achieved a response by the first efficacy evaluation. As of the cut-off date, all 7 responders were still in response and active follow up, the longest last to Day 270 (range 30-270). At a median follow-up time of 3.52 months (range 0.8-8.8), the 6-month rate of PFS was 75% (range 29.8%-93.4%). Following LUCAR-G39D, 7 of 8 patients (88%) with paired baseline and Day30 ctDNA samples had decreased ctDNA levels (median, –98%; range –23% to –100%), consistent with radiographic responses. Conclusions: LUCAR-G39D γδ CAR-T cells showed a manageable safety profile and good expansion in patients with NHL. Preliminary efficacy showed encouraging response rate and sustained durability in patients; this therapeutic strategy warrants further investigation.

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.

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.

The natural product Honokiol exhibits robust antitumor activity against a range of cancers, and it has also received approval to undergo phase I clinical trial testing. We confrmed that honokiol can promote the apoptotic death of tumor cells through cell experiments. Then siRNA constructs specific for PIAS3, PIAS3 overexpression plasmid and the mutation of the STAT3 Tyr705 residue were used to confirm the mechanism of Honokiol-induced apoptosis. Finally, we confrmed that honokiol can promote PIAS3 upregulation, in turn suppressing STAT3 Tyr705 phosphorylation through the in vivo and in vitro experiments. Honokiol was ultimately found to reduce tumor cell viability by promoting apoptosis through a mechanism dependent on the ability of Honokiol to promote PIAS3 upregulation and the selective inhibition of p-STAT3 (Tyr705) without affecting p-STAT3 (Ser727) or p-STAT1 (Tyr701) levels. PIAS3 knockdown and overexpression in tumor cells altered STAT3 activation and associated DNA binding activity through the control of Tyr705 phosphorylation via PIAS3-STAT3 complex formation, ultimately shaping Honokiol-induced tumor cell apoptosis. Honokiol was also confirmed to significantly prolong the survival of mice bearing xenograft tumors in a PIAS3-dependent fashion. Together, these findings highlight a novel pathway through which Honokiol can promote PIAS3 upregulation, in turn suppressing STAT3 Tyr705 phosphorylation and promoting the apoptotic death of tumor cells.

Hodgkin’s lymphoma（HL） is a common, malignant hematological tumor of the lymph nodes and lymphatic system, accounting for 10% of all lymphomas. HL comprises 2 main subtypes: classical HL（cHL） and nodular lymphocyte predominant HL.

Secondary central nervous system (SCNS) involvement is an infrequent but universally fatal event in diffused large B‐cell lymphoma. The occurrence rate of SCNS involvement is approximately 5% but comes with a poor prognosis ever after. However, existing risk models to predict the incidence and prognosis of these patients with SCNS involvement lack both efficiency and accuracy. Controversy has also been reported regarding which risk factor may best identify the population with a high CNS relapse rate. In this study, we retrospectively analyzed 831 patients with diffused large B‐cell lymphoma, diagnosed between March 2008 and June 2018 in Tianjin Medical University Cancer Institute and Hospital, Beijing Cancer Hospital, and Cancer Hospital of The University of Chinese Academy of Science. Risk factors and nomogram were identified and established based on Fine and Gray's competing risk analysis. Among these patients, 55 (6.6%) of them eventually developed SCNS involvement. The 1‐ and 2‐year incidence for SCNS involvement were 3.9% and 4.7%, respectively. The median time from de novo diagnosis to CNS relapse was 8 months, and the median overall survival of these patients was 28 months. Considering the competing mortality before SCNS involvement, Fine and Gray's competing risk model was performed to analyze the characteristics related to SCNS involvement, and identified risk factors as the multiple extranodal involvements, elevated LDH and AMC level, and the involvement of breast, adrenal gland/kidney, pulmonary and bone. Corresponding factors were integrated into the competing nomogram for SCNS involvement ( c ‐index = 0.778). In conclusion, we present the first predictive nomogram to evaluate the risk to develop SCNS involvement in de novo DLBCL patients, which may help in both prognostic evaluation and clinical decision for this subgroup.

Background Follicular lymphoma (FL), the most common indolent lymphoma, is a clinically and genetically heterogeneous disease. However, the prognostic value of driver gene mutations and copy number alterations has not been systematically assessed. Patients and Methods Here, we analyzed clinical-biological features of 415 FL patients to identify variables associated with disease within 24 months of first-line therapy (POD24). In addition, we applied whole exome sequencing (WES) to identify genomic alterations that predict POD24 based on 102 FL patients. Furthermore, we characterized the cellular and molecular heterogeneity within and across patients through bulk RNA sequencing and single-cell RNA sequencing. ResultsPOD24 occurred in 21% of evaluable FL patients. To further examine the effect of POD24 on OS, we used a 24-month landmark approach for Kaplan-Meier curve analysis. As expected, POD24 was related to poor OS, and the 3- and 5-year survival probabilities of patients in whom the disease progressed within the first 24 months were 89.2% (95% CI, 84.5-93.9) and 78.6% (95% CI, 70.4-86.8), respectively, compared with 98.5% (95% CI, 97.8-99.2) and 96.2% (95% CI, 95.0-97.4) in patients who were progression free at 24 months, respectively. Moreover, patients without progression at 24 months were more likely to exhibit a CR to front-line treatment (54% vs. 35%, P = 0.001) compared to the POD24 cohort. Patients with B symptoms, elevated lactate dehydrogenase and β2-microglobulin levels, unfavorable baseline haemoglobin levels, advanced stage, and high-risk FL International Prognostic Index (FLIPI) scores had an increased risk of POD24, with FLIPI being the most important factor in logistic regression. HIST1H1D, known as a driver mutation, was correlated with POD24. Gains of 6q22.2 ( HIST1H1D) and 18q21.33 ( BCL2) and loss of 1p36.13 ( NBPF1) predicted POD24 independent of FLIPI. Integration of the four variants led to the identification of 76% of POD24 patients. Gene expression profiling of FL samples showed that the POD24 cohort was significantly enriched in the inflammatory response (mediated by interferon and tumor necrosis factor), cell cycle regulation (transcription, replication and proliferation) sets and PI3K-AKT-mTOR signaling. This result was further validated with transcriptome-wide information provided by RNA-seq at single-cell resolution. ConclusionOur study, performed on a large cohort of FL patients, highlights the importance of distinctive genetic alterations and gene expression relevant to disease diagnosis and early progression.

Background: Peripheral T-cell lymphoma (PTCL) is a group of highly heterogeneous malignant tumors with poor prognosis, especially in patients with relapesd/refractory. The efficacy of traditional salvage chemotherapy in the treatment of Relapsed/Refractory (R/R) PTCL was poor, and the median OS and PFS after the first recurrence or progression were only 5.5 months and 3.1 months, respectively. There is an urgent need for more effective treatment regimens to improve the poor prognosis of these patients. Epigenetics, as a new discipline involved in gene expression regulation, provides a new approach for the occurrence, development mechanism research and clinical diagnosis and treatment of PTCL.This phase I study is a prospective, single center clinical study and designed to evaluate the safety, tolerability and efficacy of Azacitidine for injection combined with Chidamide in Relapsed/Refractory peripheral T-cell lymphoma. Methods: Eligible pts (18-75 years of age, ECOG PS 0-2) had histologically confirmed peripheral T-cell lymphoma that was either relapsed or refractory to at least 1 line of therapy. Considering that both Dose Group 2 (Azacitidine 75mg/m 2, Chidamide 20mg) and Group 3 (Azacitidine 50mg/m 2, Chidamide 30mg) adjust the dosage of a single drug based on Dose Group 1 (Azacitidine 50mg/m 2 ih d1-7, Chidamide 20mg po biw; 4 weeks/cycle), this study derived a “3+3” two-dimensional dose increasing design based on the classic “3+3” design, which allows two Dose Groups (Dose Group 2 and Group 3) to start ramp up trials simultaneously according to random principles. Enrollment in dose group 4(Azacitidine 75mg/m 2, Chidamide 30mg) can begin when either group 2 or 3 completes and no DLT occurs. The primary objectives of this study were to evaluate the safety and preliminary anti-tumor activity of Azacitidine for injection combined with Chidamide according to the Lugano 2014 criteria. Adverse events (AEs) were reported according to CTCAE v5.0. Results: Nineteen R/R PTCL pts (median age: 61 years, range: 52-71 years; male: 11 (57.9%) pts; ECOG PS=0: 10 (52.6%) pts) who was either relapsed or refractory to at least 1 line of therapy (median therapy lines:2) were enrolled. Among them, 11 pts were angioimmunoblastic T-cell lymphoma (AITL) and 8 pts were PTCL, NOS. 16 pts could evaluate the efficacy and safety. For 16 treated patients, treatment-related adverse events (TRAEs) of any grade occurred in 15 (93.7%) pts, ≥3 TRAEs occurred in 7 (43.8%) pts. The most frequent TRAEs (≥ 20%) were Pain at the injection site (n=12, 75.0%), Neutropenia (n=9, 56.3%), Erythema at the injection site (n=8, 50.0%), Nausea (n=7, 43.8%), Thrombocytopenia (n=6, 37.5%), Feeble (n=6, 37.5%), Anemia (n=5, 31.3%), Diarrhea (n=5, 31.3%), Neutropenia with fever (n=4, 25.0%). The most frequent grade ≥ 3 TRAEs (≥5%) was Neutropenia (n=3, 18.8%). 3 pts experienced TRAE leading to drug dosage adjustment. The recommended phase II dose (RP2D) was Azacitidine 75mg/m2, Chidamide 20mg (Dose Group 2). As of data cut-off date, 3 pts remained on Azacitidine for injection combined with Chidamide therapy. The objective response rate (ORR) and disease control rate (DCR) were 56.25% (9/16; 95% CI: 31.9-80.5) and 75% (12/16; 95% CI: 53.8-96.2), respectively. For AITL pts, the ORR was and DCR were 60% (6/10; 95% CI: 36.0-84.0) and 80% (8/10; 95% CI: 60.4-99.6), and 4 pts achieved CR. For all PTCL pts enrolled, Median PFS 6.45 months (95% CI: 3.97-12.7); Median OS 17.5 months (95% CI: 2.11-32.9). Conclusion: Azacitidine for injection combined with Chidamide showed a promising anti-tumor effectivity with a manageable safety profile in Relapsed/Refractory peripheral T-cell lymphoma patients, especially for AITL patients.

Epigenetic modifications contribute to lymphomagenesis. Here, we performed an expression clustering analysis and identified two epigenetic-related clusters (EC1 and EC2). EC1 presented abundant TP53, MYD88, HIST1H1D, HIST1H1C, KMT2D and EZH2 mutations and an inferior prognosis. Pathways involved in the regulation of DNA methylation/demethylation, histone methyltransferase activity, and protein methyltransferase activity were significantly enriched in EC1. However, EC2 was frequently accompanied by B2M, CD70 and MEF2B mutations, which presented with enrichments in DNA damage repair, cytokine-mediated and B-cell activated immune signaling, increased levels of CD8+ T-, γδT- and T helper-cells, as well as immune scores and immunogenic cell death (ICD) modulators. According to the prediction, EC1 was more sensitive to vorinostat, serdemetan and navitoclax. However, ruxolitinib, cytarabine and CP466722 were more suitable treatments for EC2. The novel immune-related epigenetic signature exhibits promising clinical predictive value for diffuse large B-cell lymphoma (DLBCL), particularly for guiding epigenetic therapeutic regimens. R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) based combination treatment regimens are suggested.

Background The data about the clinical features and outcomes of Chinese patients with follicular lymphoma (FL) are limited. Here, we conducted a retrospective study to explore the initial treatment strategies and clinical outcomes of Chinese patients with FL in the real world. Method This study included FL patients who were newly diagnosed in Tianjin Medical University Cancer Institute and Hospital from March 2002 to August 2020. Results A total of 926 FL patients were enrolled. The median age was 54 years old, and the majority of the Chinese FL patients had advanced-stage disease and Eastern Cooperative Oncology Group(ECOG) <1 but less frequently infiltrated bone marrow. After a median of 38-month follow-up, the 5-year progressive-free survival (PFS) and overall survival (OS) of grade1–3a were 57.8% and 88.7%, respectively, which both are similar to those reported in previous Chinese and Western studies. The co-existence at diagnosis of FL and diffuse large B-cell lymphoma (DLBCL) components (FL/DLBCL) was associated with poor outcomes. The FL grades and proportion of DLBCL component in FL/DLBCL did not have an impact on PFS and OS. The most common regimen with great efficacy and risk–benefit was RCHOP-like followed by R maintenance regimen. The 5-year cumulative hazard of histological transformation (HT) was 4.7% (95% CI, 3.5–5.9); median time to transformation was 23.5 months (range, 2–146 months) after diagnosis. Three-year survival following transformation was 55% (95% CI, 40–70). Patients with stage III–IV, elevated β2 microglobulin (β2-MG), and B symptoms seemed to be more prone to progress within 24 months of frontline therapy (POD24). The FLIPI-2 showed the highest specificity to predict POD24, reflecting the prediction of correctly classifying as low-risk patients, but the FLIPI had the highest sensitivity to predict the risk of progression for critical patients. Conclusions We revealed the clinical characteristics and outcomes of FL patients in the real world in China, which may provide novel data on prognostic factors and primary treatment of FL, applicable to routine clinical practice.

Background: Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous lymphatic malignancy. The role of TP53 gene alterations in DLBCL remains unclear. Methods: We performed a comprehensive analysis of the genomic characteristics of TP53 through targeted next-generation sequencing (n=176), RNA-sequencing (n=152), and circulating tumor DNA sequencing (n=38). Results: TP53 was frequently mutated in DLBCL; most TP53 mutations occurred in the DNA-binding domain (DBD). However, TP53 alone is insufficient to effectively differentiate the risk of DLBCL, even when only considering mutations in the DBD region. However, CD58 mutations, which are mutually exclusive from TP53 mutations, in combination with TP53 mutations, could significantly differentiate the prognosis of DLBCL. The survival of patients with either one of the mutually exclusive mutation patterns, namely, TP53MUT&CD58WT or TP53WT&CD58MUT, was inferior to those harboring both wild-type TP53 and CD58. Notably, patients with the TP53WT&CD58MUT mutation pattern had the worst outcome and were characterized by an enhanced immune escape, including features such as the abundant infiltration of inflammatory cells and upregulation of inhibitory immunomodulatory molecules; these patients represent the candidate populations for immune therapy. Conclusions: Our findings indicated that the mutation patterns of TP53 and CD58 accurately stratified patients with DLBCL to permit the optional immunotherapy.

头颈部鳞癌是一种异源性疾病,类型复杂而多样.不仅对患者外貌和基本生理功能、感觉功能和语言功能产生破坏和影响,还影响患者生活质量.尽管近年来对头颈部鳞癌的诊治取得显著进展[1],但由于其是易局部复发或远处转移的难治性恶性肿瘤,绝大多数复发性头颈部鳞癌患者需要接受姑息性系统治疗,但目前可用的系统治疗方案疗效仍不理想.

The mantle cell lymphoma (MCL) International Prognostic Index (MIPI) and combined MIPI (MIPI-c) are commonly used for risk classification of MCL patients. However, these indexes lack immune-related parameters. The purpose of this study was to develop a novel prognostic model that integrated clinical and immune parameters. A total of 189 patients with newly diagnosed MCL from January 2010 to June 2020 were enrolled in our study. A nomogram and immune-related prognostic index (IRPI) were established to predict the overall survival (OS) of patients according to univariate and multivariate analyses. Discrimination and calibration were used to compare the prognostic performance of the IRPI, MIPI, and MIPI-c. External validation was performed based on validation dataset (n = 150) from two other centers. The results for the training dataset indicated that B symptoms, platelet count, B2M level, CD4+ T-cell count<26.7% and CD8+ T-cell count>44.2% were predictors for OS. All the prognostic factors were integrated into the nomogram. For the overlap of confidence intervals of each variable, we assigned one point for each factor. The IRPI categorized patients into three risk categories: a score of zero indicated low risk, a score of one or two indicated intermediate risk, and a score of ≥3 indicated high risk. The IRPI showed better discrimination and calibration power than the MIPI and MIPI-c in the training dataset and validation dataset. The novel IRPI is a refined risk stratification index and reflects the strong complementary prognostic effects between clinical and immune parameters in MCL.

Progression of disease within 24 months (POD24) is strongly associated with a poor outcome in patients with follicular lymphoma (FL). Our study aimed to identify the potential risk factors for POD24 in patients with FL. Medline, EMBASE and the Cochrane Library were systematically searched from the earliest record to September 2020. Studies investigating the prognostic factors for POD24 in patients with newly diagnosed grade 1-3a FL were included. Among 10,014 pieces of literature, a total of 90 studies investigating 82 risk factors were included for qualitative analysis. Meta-analyses were performed in 31 studies with 11 factors. Results showed that elevated sIL-2R, β2m and LDH, total metabolic tumour volume > 510 cm3, vitamin D < 20 ng/mL, grade 3a and lymphoma-associated macrophages/high-power field ≥ 15 were significantly associated with an increased risk of POD24. No significant association was found between POD24 and the ALC/AMC ratio, sex, T effector signature or EZH2 genetic alteration. Additionally, minimal residual disease, Ki-67, PD-1 and TP53 were analysed narratively. Overall, this is the first study that comprehensively analysed the prognostic factors associated with POD24 in FL patients. We have confirmed the significance value of several common prognostic factors as well as others not commonly included in clinical study, helping to construct an integrated and more efficient model.

BGB-3111, a novel Bruton's tyrosine kinase (BTK) inhibitor, shows promising anti-cancer effects in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), mantle cell lymphoma (MCL), and Waldenstrom macroglobulinemia (WM). This study aimed to investigate the anti-cancer effects of BGB-3111 combined with bortezomib (BTZ) against the BTK-expressing MCL. We found that BTK, which was overexpressed in 59.4% of patients with MCL, was mainly characterized by high Ki67 and elevated MIPI scores. BGB-3111 strongly inhibited cell proliferation, induced cell cycle arrest in the G1/G0-phase, and promoted cell apoptosis in the MCL cells expressing BTK. BGB-3111 provides better safety than another BTK inhibitor, ibrutinib as ibrutinib inhibits the inducible T-cell kinase (ITK) as an off-target effect but BGB-3111 does not inhibit ITK. Low doses of BTZ enhanced the anti-cancer effect induced by the low dose of BGB-3111 by downregulating the expression levels of PARP and Bcl-2 and increasing the expression levels of cleaved PARP and cleaved caspase-9. In addition, low doses of BGB-3111, but not of BTZ, inhibited BTK phosphorylation. However, low-doses of BTZ strengthened the anti-cancer effect induced by the low-doses of BGB-3111 via synergistically suppressing the IκBα and P65 phosphorylation. Taken together, our findings validate that BGB-3111 is a novel and effective BTK inhibitor for MCL-expressing BTK. Hence, it can be harnessed as a potential therapeutic strategy through a combinatorial treatment comprising low-dose BGB-3111 and low-dose BTZ to gain strong anti-cancer effects and better safety for MCL patients.