The Smart Start trial demonstrated the combination of ibrutinib, rituximab, and lenalidomide resulted in impressive efficacy in newly diagnosed non-GCB diffuse large B-cell lymphoma (DLBCL). However, ibrutinib was associated with increased unexpected toxicity in elderly patients. Zanubrutinib and orelabrutinib have better target selectivity. This single-center, real-world, off-label study retrospectively included patients with newly diagnosed DLBCL who received SMART regimen (rituximab, lenalidomide plus BTK inhibitor) between January 2021 and June 2024. The outcomes included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. A total of 84 patients were analyzed for efficacy with a median follow-up of 13.5 (range, 2.5–42.2) months. The OR2 regimen (orelabrutinib, rituximab and lenalidomide) was administered to 60.7

Lymphoma-associated haemophagocytic lymphohistiocytosis (HLH) represents a rare and life-threatening hyperinflammatory syndrome with a dismal prognosis, largely due to its poorly understood pathogenesis and unclear distinctions from non-lymphoma associated HLH (NLAHS). To elucidate these differences, we performed an integrated multiomics analysis on peripheral blood samples from patients with newly diagnosed lymphoma-associated HLH (LAHS), NLAHS and healthy controls (NC). Single-cell ribonucleic acid sequencing (scRNA-seq) analysis (4 LAHS, 3 NLAHS, 2 NC) revealed that LAHS is characterized by enhanced glycolytic activity in significantly expanded monocyte populations, notably within a distinct subset of pituitary tumor-transforming gene 1+ (PTTG1+) monocytes. Metabolomic profiling (21 LAHS, 11 NLAHS, 7 NC) further confirmed elevated levels of glycolytic products, such as lactate and pyruvate. Clinically, hyperlactataemia (>5.1 mmol/L, n = 84) emerged as a significant independent predictor of poor survival in LAHS, with a median overall survival of only 43.5 days (p < 0.001). Remission induced by treatment was associated with a reversal of this hypermetabolic phenotype. Cell communication analysis revealed upregulated thrombospondin signalling from PTTG1+ monocytes, linked to glycolytic activity. Our findings indicate that LAHS is characterized by a pronounced Warburg-like metabolic state, primarily involving glycolytic monocytes. Hyperlactataemia is associated with adverse outcomes and may guide the development of novel therapeutic strategies targeting immunometabolic pathways.

Treatment options for relapsed or refractory extranodal natural killer/T-cell lymphoma (R/R ENKTL) remain limited. In this phase 1b/2 trial (NCT05464433), we evaluated the safety and efficacy of liposomal mitoxantrone (Lipo-MIT) plus anti-PD-1 tislelizumab in this setting. During dose escalation, patients received Lipo-MIT (16 or 20 mg/m2) plus tislelizumab using a 3 + 3 design, followed by dose expansion at the recommended phase 2 dose (RP2D). The primary endpoint of the dose-escalation phase was dose-limiting toxicities (DLTs), which were assessed to determine the RP2D. The primary efficacy endpoint of the dose-expansion phase was the best complete response (CR) rate. Between July 23 2022 and November 28 2024, 40 patients received study treatment (dose-escalation, n = 6; dose-expansion, n = 34). No DLTs were observed and the RP2D of Lipo-MIT was 20 mg/m2. The prespecified primary efficacy endpoint was met, with a CR rate of 53% (21/40; one-sided 95% lower confidence bound, 38%). The median progression-free survival (secondary endpoint) was 8.2 months (95% confidence interval, 6.1-not estimable) after a median follow-up of 15.3 months. The most common grade ≥ 3 adverse events were leukopenia (53%), neutropenia (40%), and febrile neutropenia (18%). In conclusion, Lipo-MIT plus tislelizumab showed promising anti-tumor activity with an acceptable safety profile in R/R ENKTL.

Peripheral T-cell lymphoma (PTCL) is a heterogeneous subtype of non-Hodgkin lymphoma with a poor prognosis. Red blood cell distribution width (RDW) is a hematological parameter reflecting variability in erythrocyte volume and has been associated with prognosis in various diseases. Therefore, we conducted a retrospective study on 629 newly diagnosed patients with PTCL to explore the relationship between baseline RDW, prognosis, and response to first-line treatment. The cutoff value for baseline RDW was 14.45

7004 Background: Peripheral T-cell lymphoma (PTCL) is a heterogeneous type of aggressive non-Hodgkin lymphoma with poor prognosis. CHOP-based regimens are most widely used for PTCL yet response rates and long-term survival remain unsatisfactory. Linperlisib, a selective PI3Kδ inhibitor, has shown encouraging antitumor activity with manageable safety profile in relapsed or refractory PTCL. This study aimed to evaluate the efficacy and safety of linperlisib plus CHOP (L-CHOP) as first-line treatment for newly diagnosed PTCL. Methods: The LINCH trial (NCT05949944), a multi-center, single-arm phase Ib/II study, enrolled patients aged ≥ 18 years with newly diagnosed PTCL. In phase Ib, 6 patients received 6 cycles of L-CHOP to determine the recommended phase II dose (RP2D). In phase II, patients received L-CHOP at the RP2D. Following 6 cycles, patients achieving complete response (CR) or partial response (PR) continued linperlisib maintenance until progression or intolerable toxicity or up to 24 months. The primary endpoints were the DLTs incidence (phase Ib) and the CR rate after 6 cycles of L-CHOP (phase II). Preliminary results were reported. Results: From August 15, 2023 to November 15, 2025, 44 patients were enrolled, including 6 patients in phase Ib. The median age was 57 years (range 18–77); 28 patients were males (63.6%). Most patients (n = 35, 79.5%) had stage III-IV disease, and 17 (38.6%) had an IPI score of 3–5. In phase Ib, one DLT (grade 3 febrile neutropenia) occurred in cycle 1, confirming linperlisib 80 mg once daily as RP2D. At the data cutoff on December 30, 2025, efficacy was evaluable in 34 patients (26 completed six cycles; 8 discontinued early), with 10 still receiving induction therapy. After six cycles of combination therapy, 19 patients (55.9%) achieved CR and four achieved PR, resulting in an objective response rate (ORR) of 67.6%. Treatment-emergent adverse events (TEAEs) occurred in 32 patients (94.1%); hematologic toxicity were common: neutropenia (n = 24, 70.6%), leukopenia (n = 21, 61.8%), anemia (n =14, 41.2%). Grade ≥ 3 TEAEs occurred in 19 patients (55.9%), most frequently neutropenia (n = 13, 38.2%), leukopenia (n = 10, 29.4%) and pneumonia (n = 4, 11.8%). Conclusions: Preliminary results from LINCH study suggest that linperlisib combined with CHOP as first-line treatment for PTCL achieved promising efficacy and manageable safety. A randomized controlled trial evaluating linperlisib plus CHOP versus CHOP in patients with newly diagnosed PTCL has been initiated (NCT06548347). Clinical trial information: NCT05949944 . Baseline characteristics. Characteristics Patients (n=44) Age, years (median [IQR]) 57 (18-77) Sex MaleFemale 28 (63.6%)16 (36.4%) ECOG PS 0-12 39 (88.6%)5 (11.4%) Lugano stage I-II III-IV 9 (20.5%)35 (79.5%) Pathological types AITLPTCL-NOSALCLTFHL-NOSMEITLSPTCL 23 (52.3%)14 (31.8%)3 (6.8%)2 (4.5%)1 (2.3%)1 (2.3%)

Very old or frail patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) frequently cannot tolerate full-dose R-CHOP, and long-term control with R-miniCHOP is suboptimal. We assessed a sequential, chemotherapy-limiting regimen using zanubrutinib, lenalidomide, and rituximab (ZR2) induction followed by response-adapted ZR2-miniCHOP. This single-center, open-label, investigator-initiated phase 2 trial enrolled untreated patients aged ≥ 80 years, or 60–79 years with ECOG performance status ≥ 2. All patients received two 21-day cycles of chemotherapy-free ZR2 (zanubrutinib 160 mg twice daily continuously; lenalidomide 25 mg once daily on days 1–10; rituximab 375 mg/m2 on day 0), then four cycles of ZR2 plus reduced-dose miniCHOP. PET/CT after cycle 6 determined consolidation: two cycles of ZR2 maintenance for complete responders or two additional cycles of ZR2-miniCHOP for partial responders. Primary endpoints were overall response rate (ORR) and complete remission (CR) rate after six cycles; secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Forty-eight patients were treated (median age 78 years; 45.8

Whether TP53 mutation can serve as a simplified prognostic surrogate for complex genomic classifiers in diffuse large B-cell lymphoma (DLBCL) remains unclear. we comprehensively analyzed a retrospective cohort of 444 newly diagnosed DLBCL patients. TP53 mutation was an independent prognostic factor for inferior overall survival (OS) and progression-free survival (PFS) (both P < 0.001), correlating with inferior response to R-CHOP and enrichment in refractory/relapsed disease. Furthermore, multivariate analysis revealed that the adverse prognostic effect of TP53 mutation was predominantly driven by its impact within the germinal center B-cell-like (GCB) subtype, as evidenced by a significant statistical interaction. Notably, the combination of TP53 mutation and double-expression lymphoma (DEL) identified an ultra-high-risk group with synergistic poor survival. The prognostic impact was not modified by the specific protein domain, mutation burden, or gain- versus loss-of-function nature of the mutations. However, a high variant allele frequency (VAF) ≥ 53

ABSTRACT Background Continuous venetoclax‐azacitidine (VA) therapy is currently the major intervention for elderly or unfit acute myeloid leukemia (AML) patients. However, moderate chemotherapy with finite‐duration VA could achieve comparable or superior efficacy to infinite‐duration VA. Additionally, umbilical cord blood (UCB) transfusion improves clinical safety for elderly patients. Therefore, this single‐center study presents an improved approach: A finite‐duration VA and decitabine priming with intermediate‐dose cytarabine followed by UCB infusion. Methods We included elderly AML patients who underwent the treatment between March 2021 and May 2024. Induction and maintenance regimens were VA. Our consolidation therapy involved intravenous decitabine (20 mg/m2 d1–3), intermediate‐dose cytarabine (1.0 g/m2 q12h d4–5), with subsequent UCB infusion (1.5% ± 25% × 107/kg) d7. Our endpoints included duration of response (DOR), overall survival (OS), and safety. Results We analyzed 16 patients with a median follow‐up of 53.6 months (95% CI: 36.2–71.0 months), and 7 out of 16 participants were at adverse risk. The median VA cycle number prior to disease relapse was 5 (IQR: 4–6). The median DOR was 17.4 months (95% CI: 7.3–27.5 months), with a 1‐year DOR rate of 68.8% and a 2‐year DOR rate of 35.2%. The median OS was 24.9 months (95% CI: 9.8–40.1 months), with a 1‐ and 2‐year OS rate of 100% and 55.6%. Specifically, among the 8 patients with IDH1/2 mutations, 4 experienced sustained remission, with 1‐year OS of 100%. Hematological and non‐hematological toxicities remained manageable during the consolidation phase. Conclusions We demonstrated prolonged survival, particularly in patients with IDH mutations, using the modified intervention. This approach holds significant value for elderly patients with untreated AML who are unfit for standard treatments.

Blastoid and pleomorphic mantle cell lymphoma (B/P-MCL) represents a high-risk subtype of hematological malignancy with an unfavorable prognosis. We conducted a retrospective analysis of 76 patients with classic MCL and 81 patients with B/P-MCL between January 2010 and May 2024 to investigate clinical characteristics, outcomes, and prognostic factors. Ki-67 ≥ 30

Introduction Angioimmunoblastic T-cell lymphoma (AITL) represents an aggressive malignancy derived from follicular helper T cells. Characteristic genetic mutations, including alterations in TET2, DNMT3A, IDH2, and the RHOA G17V variant, underpin the pathogenesis of this lymphoma subtype. Comprehensive investigations underscore the transformative potential of epigenetic-targeting agents in exerting pronounced anti-lymphoma activity.Methods This prospective study evaluates the therapeutic potential and safety profile of azacitidine combined with CHOP chemotherapy (ACHOP) in previously untreated AITL patients. Inclusion criteria encompassed patients aged 18–75 years with untreated AITL and an Eastern Cooperative Oncology Group (ECOG) performance status of 0–3. The therapeutic regimen administered azacitidine (75 mg/m², days 1–5) alongside CHOP chemotherapy every 21 days for four cycles. Patients achieving complete remission (CR) proceeded to an additional four ACHOP cycles, followed by recommendations for autologous stem cell transplantation (ASCT) in eligible patients aged under 65 years. Maintenance therapy with the histone deacetylase (HDAC) inhibitor chidamide was advised for two years for all participants. The study's primary endpoint assessed the CR rate, while secondary endpoints included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety evaluation.Results Fifty-two treatment-naïve AITL patients were sequentially enrolled, with a median age of 63 years (range: 41–75 years). Advanced disease was prevalent, with 96.2% (50 patients) classified as stage III or IV per the Ann Arbor staging system. Constitutional symptoms such as high-grade fever were present in 13 patients at baseline. Extranodal involvement was noted in 75% (39 patients), and 80.8% (42 patients) presented with an International Prognostic Index (IPI) score ≥2. Elevated Epstein-Barr virus (EBV) DNA levels (>500 copies/mL) were detected in 36 participants. All 52 participants received at least one cycle of azacitidine plus CHOP as of July 11, 2025. Of 48 evaluable patients, an ORR of 87.7% (43/49) was observed, comprising a CR rate of 73.4% (36/49) and a partial remission (PR) rate of 14.3% (7/49). Eleven patients experienced CR relapse, with seven relapsing within 12 months. The median follow-up period was 22 months. Median PFS reached 27 months, whereas median OS had not been reached at analysis time. Two-year PFS and OS rates stood at 63.2% and 83.7%, respectively. The ACHOP regimen displayed an acceptable safety profile. Common adverse events included leukopenia, anemia, and thrombocytopenia. Grade 3 or higher toxicities predominantly involved neutropenia, thrombocytopenia, infections, and pneumonia. No treatment-related deaths occurred.Conclusions The combination of azacitidine and CHOP presents a compelling therapeutic option with robust efficacy and manageable toxicity as a first-line treatment for AITL.

The absence of a standard first-line treatment for marginal zone lymphoma (MZL) and the toxicities of existing systemic therapies have inspired the exploration of novel regimens. In recent years, Bruton's tyrosine kinase inhibitors (BTKis) have demonstrated durable responses with a favorable benefit-risk profile across all MZL subtypes in the relapsed/refractory setting. Orelabrutinib is a novel BTK inhibitor with higher selectivity and fewer off-target than other BTK inhibitors. The National Medical Products Administration has approved it for the treatment of patients (pts) with MZL who have received at least one prior treatment. Aims:To evaluate the efficacy and safety of orelabrutinib plus bendamustine-rituximab or obinutuzumab followed by orelabrutinib maintenance in untreated MZL. Optimize was a multicenter, open-label, single-arm, phase II study (NCT06504940) that recruited treatment-naïve pts with MZL from 7 centers in China. Fit pts aged 18-70 years (group A) received 3 cycles of induction treatment with orelabrutinib (150 mg/day) plus bendamustine (70 mg/m2 on days 1-2) and rituximab (375 mg/m2 on day 0), while pts aged ≥70 years or unfit pts aged <70 years (group B) received 6 cycles of orelabrutinib (150 mg/day) plus obinutuzumab (1000 mg on days 1, 8, and 15 of cycle 1 and day 1 of cycles 2-6) every 4 weeks. Subsequently, pts without disease progression in both groups continued orelabrutinib maintenance at the same dose and scheduled for up to 21 (group A) or 18 (group B) cycles. The primary endpoint was complete response rate (CRR) at the end of induction treatment for both groups. Key secondary endpoints in both groups were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. As of Jul 2025, a total of pts were enrolled (group A, n=19; group B, n=6). The median age of overall population was 60.0 years (group A, 59.0 years; group B, 70.5 years), and 48% of pts were male (group A, 57.9%; group B, 16.7%). The majority of pts presented with MALT lymphoma (overall, 64.0%; group A, 63.2%25; group B, 66.7%) and had Ann Arbor stage II-IV disease (overall, 80%; group A, 84.2%; group B, 66.7%). International Prognostic Index (IPI) score of 2/3 and Ki-67 expression of >20% were reported in 48.0% (group A, 47.3%; group B, 50%) and 24.0% (group A, 21.1%; group B, 33.3%) of pts, respectively. At the end of induction treatment, efficacy evaluation was conducted in 12 pts in group A and 3 pts in group B. The CRR was 75% (9/12) in group A and 66.7% (2/3) in group B. The ORR was 93.3% and the CRR was 93.3% in the overall population. At the data cutoff, the median PFS and OS remained immature. Grade 3-4 adverse events (AEs) were occurred in 43.7% of pts overall (group A, 46.2%; group B, 33.3%).The primary toxicities were hematologic, including neutropenia, thrombocytopenia, and leukopenia. No BTKi-related AEs, such as atrial fibrillation or bleeding, were observed. Conclusion:Orelabrutinib combined with bendamustine-rituximab or obinutuzumab followed by orelabrutinib maintenance was effective and well-tolerated in untreated pts with MZL. The study is ongoing, with updated efficacy and safety data to be released in the future.

INTRODUCTION:High-mobility group box 1 (HMGB1) protein plays a significant role in cancer development and treatment response. The current research on the role of HMGB1 in lung cancer and its treatment outcomes is limited and inconsistent. This exploratory study investigated the association between HMGB1 common genetic variants and lung cancer susceptibility, as well as cisplatin chemotherapy response, in a Chinese cohort. METHODS:The current study included 106 individuals diagnosed with lung cancer and 93 healthy subjects, all of whom were part of a Chinese population cohort. HMGB1 polymorphisms (rs1045411, rs1412125, rs2249825, and rs1360485) were genotyped using the TaqMan single-nucleotide polymorphism typing method. HMGB1 gene expression in the lung tissue of patients was quantified using real-time PCR. All patients were administered cisplatin, and their response to the drug was evaluated. All statistical analyses were performed using GraphPad Prism v10. RESULTS:The control group exhibited a higher frequency of heterozygous variants for HMGB1 polymorphisms rs1045411 (p = 0.01, odds ratio [OR] = 0.45) and rs1412125 (p = 0.03, OR = 0.46) than the patients. Moreover, the combined mutant genotypes for HMGB1 rs1045411 (p = 0.0001, OR = 0.15) and rs2249825 (p = 0.003, OR = 0.19) exhibited favorable responses to cisplatin treatment. Moreover, the wild-type variants of rs1045411 and rs2249825 exhibited higher HMGB1 expression than the mutants; however, this difference was not statistically significant. CONCLUSION:This preliminary investigation indicated potential associations between HMGB1 genetic variants and lung cancer susceptibility and treatment response. These exploratory findings necessitate further validation through larger multicenter studies incorporating functional assays to elucidate the biological significance and clinical utility of HMGB1 polymorphisms in the management of lung cancer.

Introduction Myeloid/lymphoid neoplasms with FGFR1 rearrangement (MLN-FGFR1) constitute an aggressive stem-cell derived myeloproliferative disorder driven by translocations involving the FGFR1 locus at chromosome 8p11-12. FGFR1 tyrosine kinase is constitutively activated, triggering hematopoietic malignancies spanning chronic phase (CP) of a chronic myeloid neoplasms, and blast phase (BP) of AML/ALL/MPAL, and/or extramedullary disease (EMD). Current therapeutic options for MLN-FGFR1 remain limited and carry a poor prognosis. Olverembatinib (HQP1351), a novel third-generation multi-target TKI was evaluated for antitumor activity in both preclinical and clinical settings in this study. Methods Preclinical Study Two most common FGFR1 fusions of ZNF198::FGFR1, BCR::FGFR1were transfected into Ba/F3 cells and treated with olverembatinib, ponatinib, and pemigatinib. In vivo efficacy were tested in Ba/F3 xenograft models, and olverembatinib was administered via oral gavage at 3-20 mg/kg every other day. Longitudinal monitoring included daily observation of changes in physical condition, weekly assessment of survival rates, peripheral blood immunophenotyping by flow cytometry, and bioluminescent imaging of tumor burden. Clinical Study A phase 2, open-label, multicenter study was performed to evaluate the efficacy and safety of olverembatinib in adults with newly diagnosed or relapsed MLN-FGFR1. For treatment, patients in CP received olverembatinib 40 mg on alternate days (QOD) orally, whereas those in BP received a combination with regimens for AML or ALL. Allo-HSCT was recommended for all eligible patients following at least 2 years post-transplant maintenance with olverembatinib. The primary endpoint was the complete remission (CR) rate. Key secondary endpoints included CCyR, CMR, survival and adverse events(AEs). Results Preclinical Study Olverembatinib demonstrated potent anti-proliferation activity in Ba/F3 cells transformed by ZNF198::FGFR1 and BCR::FGFR1, with IC50 at 1 and 6 nM, respectively, which is significantly lower than that of ponatinib, and comparable to that of pemigatinib. Apoptosis analysis showed that olverembatinib induced apoptosis in these cells in a dose-dependent manner. In Ba/F3 mouse models, olverembatinib given at 3-20 mg/kg (QOD) dose-dependently increased the median survival time of mice by 2-8.5 days (P < 0.05) and 1-7 days (P < 0.01) respectively. Notably, in models expressing BCR::FGFR1, olverembatinib at 20 mg/kg increased the median survival time more significantly than pemigatinib at its efficacious dose (7 vs. 3 days). Mechanistically, olverembatinib inhibited phosphorylation of FGFR1, and downstream protein STAT5, STAT3, AKT and ERK1/2, increased cleavage of caspase-3 and PARP-1, suggesting apoptosis induction. We are exploring the binding site of olverembatinib into FGFR1, which will be reported in the final report. Clinical Study - Baseline characteristics As of July 30, 2025, 17 patients were enrolled and 16 patients were evaluated for efficacy. 4 (25.0%) were in CP disease, 12 were in BP disease (including 7 CP with EMD, 3 BP without EMD, 1 BP with EMD, and an EMD only). The median age was 45 years, and 7(43.8%) patients were men. 10 patients (62.5%) had peripheral blood eosinophilia. ZMYM2 was the most commonly observed fusion partner, as detected in 11(68.8%) patients. RUNX1 mutation was detected in 8/13 (61.5%) patients. At this writing, 5 patients had bridged to allo-HSCT upon achievement of CR/CHR. -Response 14 patients (87.5%) achieved CR/CHR, among whom 1 achieved CCyR and 1 achieved CMR at 2 months' evaluation. 2 patient achieved PR. Best responses were 5 CMR, 3 CCyR, 1 PCyR, 7 CR/CHR. With a median (range) follow-up of 9.5 (2-36) months, 11 patients were still alive with no detected disease. Among the 5 patients who had received HSCT, 4 had CMR, 1 died of transplant-related infection. -Adverse Events AEs in 8 patients who were treated with olverembatinib alone, were evaluated. ≥Grade 3 AEs were reported in 5 patients. One patient reported grade 4 neutropenia, one grade 3 platelet count reduction, one grade 3 hypertension and one grade 3 cerebral infarction. Conclusions Olverembatinib was highly effective and well tolerated in patients with MLN-FGFR1 in both preclinical and clinical settings. Combined chemotherapy was preferable in patients with BP disease, and allo-HSCT remained an important strategy for extending survival.

Background: Patients with relapsed or refractory (R/R) aggressive B-cell lymphomas, particularly diffuse large B-cell lymphoma (DLBCL), have a poor prognosis. Glofitamab, a CD20xCD3 bispecific antibody, has demonstrated significant efficacy in pivotal clinical trials. However, a pressing need exists for real-world evidence on its effectiveness and safety, especially within heavily pre-treated and heterogeneous patient populations. This study aimed to evaluate the outcomes of glofitamab-based therapy in a real-world cohort of Chinese patients with R/R aggressive B-cell lymphomas and to identify predictive factors for response. Methods: This retrospective, multicenter study enrolled 65 patients with R/R aggressive B-cell lymphoma treated with glofitamab-based regimens. We collected baseline demographic, clinical, and treatment data. The majority of patients received glofitamab as monotherapy (50.8%) or in combination with PD-1 inhibitors (27.7%). Primary efficacy endpoints were the overall response rate (ORR) and complete response (CR) rate. Survival outcomes, including progression-free survival (PFS) and overall survival (OS), were analyzed using the Kaplan-Meier method. Safety was evaluated based on reported adverse events (AEs). Univariate logistic regression analyses were performed to identify predictors for achieving a CR. Results: A total of 65 patients were included in the analysis. The cohort was characterized by high-risk features: 72.3% were older than 60 years, 80.7% had Ann Arbor stage III-IV disease, the median treatment line 4 (range 2-11), and 50.9% had refractory disease. The predominant histology was DLBCL (83.1%), with 67.2% being of the non-germinal center B-cell (non-GCB) subtype. Among 43 efficacy-evaluable patients, the best ORR was 67.4% (95% CI: 51.5%-80.9%), with a CR rate of 46.5%. For the 39 patients in the survival analysis, the median follow-up was 5.88 months (95% CI: 4.24-9.86). The median progression-free survival (PFS) was 6.0 months (95% CI: 4.3-NA) , and the median overall survival (OS) was 13.9 months (95% CI: 12.5-NA). The treatment was well-tolerated, with the most frequent grade ≥3 AEs being anemia (18.2%), neutropenia (15.9%), and leukopenia (13.6%). Cytokine release syndrome (CRS) occurred in 18.2% of patients, and was predominantly low-grade. Severe, grade ≥3 CRS was observed in only 4.5% of patients. Univariate analysis revealed that relapsed disease (vs. refractory, OR=5.06, p=0.020) and the absence of bone marrow involvement (OR=4.44, p=0.039) were associated with a higher likelihood of achieving CR.Conclusion: In this multicenter, real-world study of Chinese patients with R/R aggressive B-cell lymphoma, glofitamab-based therapy demonstrated substantial efficacy, achieving high response rates and promising survival outcomes. At the same time, the safety profile was predictable and manageable, with a low incidence of severe CRS. Our findings suggest that glofitamab is a valuable therapeutic option for this challenging patient population. Disease status (relapsed vs. refractory) and bone marrow involvement were factors significantly associated with complete response in univariate analysis, warranting further validation.

Abstract A deeper understanding of the immune landscape in patients with idiopathic multicentric Castleman disease (iMCD) is essential to establish early prognostic stratification and uncover novel therapeutic targets. We used single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) from a cohort of 15 patients with iMCD and 4 healthy controls. To explore the sources of interleukin-6 (IL-6), we included lymph node and bone marrow samples for comparison with PBMCs. Our results indicate that IL-6 primarily originates from the lymph nodes, particularly from activated B cells. Similarly, in peripheral blood, activated B cells are also the main source of IL-6. IL-6 receptor is primarily expressed in monocytes in PBMCs, with CCL monocytes showing the strongest activation of the IL-6 signaling pathway. This suggests that CCL monocytes in iMCD may play an important role in driving peripheral inflammatory storms. CellChat analysis reveals that during disease flares, CCL monocytes interact with specific natural killer (NK)/NKT cells through enhanced type II interferon (IFN-II) signaling, whereas this interaction significantly diminishes during remission, indicating a significant role for IFN-II in the pathogenesis of iMCD. Notably, serum IFN-γ levels positively correlate with both disease severity and treatment resistance, a finding validated by a large independent iMCD cohort. Our findings confirm that the IL-6 pathway remains central to iMCD pathogenesis and highlight a significant role for IFN-II pathway activation in amplifying inflammatory storms. Our findings provide valuable biomarkers for assessing disease severity and identify new therapeutic targets for iMCD.

Erythropoiesis-stimulating agents (ESAs) achieve hematological improvement-erythroid (HIE) in only 30% of ESA-naïve lower risk myelodysplastic syndrome (LR-MDS) patients with anemia, highlighting the need for developing novel drugs or new treatment strategies to improve the outcome of these patients. We conducted this multicenter, single-arm trial to investigate the efficacy and safety of a triple regimen consisting of recombinant human erythropoietin (rhEPO), all-trans retinoic acid (ATRA) and testosterone undecanoate in patients with anemia due to lower-risk MDS based on Revised International Prognostic Scoring System. Eligible patients received rhEPO 10000 IU/day, oral ATRA 25 mg/m2/day and oral testosterone undecanoate 80 mg twice daily for 12 weeks. The primary endpoint was the proportion of patients achieving HI-E during 12 weeks of treatment. Of 52 eligible patients, 32 (61.5%, 95%CI 48.0%-73.5%) achieved HI-E, meeting the primary endpoint. Fifteen patients (65.2% [15/23]) with baseline serum erythropoietin ≤500 IU/L had HI-E versus 58.6% of those (17/29) with baseline serum erythropoietin >500 IU/L. More patients with very low or low risk had HI-E than those with intermediate risk (73.3% vs. 45.5%, P = 0.041) and fewer patients with mutated ASXL1 had HI-E than those with wildtype ASXL1 (33.3% vs. 70.0%, P = 0.040). The regimen had an acceptable safety profile compatible with individual agents. In conclusion, the triple regimen of rhEPO combined with ATRA and testosterone undecanoate attained HI-E in approximately 61.5% of patients regardless of baseline serum EPO levels, supporting further development of this regimen for LR-MDS patients with anemia. This study was registered at CHICTR.ORG.CN as ChiCTR2000032845.