7073 Background: Mesutoclax (ICP-248) is a next-generation BCL2 inhibitor, and orelabrutinib is a marketed BTK inhibitor for CLL/SLL, MCL, and MZL. However, the clinical activity of their combination in these malignancies remains undefined. This analysis evaluated the combination of mesutoclax and orelabrutinib across B-cell malignancies. Methods: Patients with relapsed and refractory (R/R) MCL, MZL were enrolled in a phase 1 study (NCT05728658), and treatment-naive (TN) CLL/SLL were enrolled in a phase 2 study (NCT06378138). R/R MCL and MZL patients received continuous daily mesutoclax (125 mg) and orelabrutinib (150mg) from cycle 1 day 1 continuously until disease progression or unacceptable toxicity. For CLL/SLL patients, induction therapy with orelabrutinib (150 mg QD, Cycles 1-17) was administered first, followed by mesutoclax (100 mg or 125 mg QD, Cycles 3-14). The orelabrutinib treatment continued beyond cycle 17 if the uMRD (≤10-4) was not achieved. Mesutoclax was implemented with a ramp-up schedule in all patients to mitigate the risk of TLS. Results: As of 05 Jan 2026, 60 patients were enrolled and treated in the studies: 8 R/R MCL, 10 R/R MZL, and 42 TN CLL/SLL (mesutoclax 100 mg, n=21; 125 mg, n=21). In R/R patients, the median number of prior lines of therapy was 1 (1-4). 6 (33.3%) were refractory to the last line of therapy. For TN CLL/SLL, 76.2% (32/42) of patients had moderate or high TLS risk, and 14.3% (6/42) had TP53 mutation or del (17p). Among 5 MCL and 8 MZL patients who had at least one disease evaluation, the overall response rate (ORR) was 100%, with CRR of 100% and 50%, respectively. Five patients (38.5%) achieved peripheral blood (PB) uMRD. In the 21 CLL/SLL patients receiving mesutoclax 125 mg, the ORR was 100% and the CRR was 38.1%, and the peripheral blood uMRD rate at 36-week was 65%. The median time to CR was 3.7 months in R/R group and 7.1 months in TN group. The 12-month PFS rate was 100% in CLL/SLL, while data for MCL and MZL are immature due to short follow-up. As the safety data cutoff (31 Dec 2025), the combination of mesutoclax and orelabrutinib was well tolerated with a favorable safety profile, and no new safety signals were identified compared to either agent as monotherapy. Most TEAEs were grade 1-2, with no TEAEs leading to drug discontinuation or death reported. The most common grade ≥3 TEAEs include neutrophil count decreased (35%), platelet count decreased (11.7%). Notably, no grade ≥3 anemia was reported. No clinical or laboratory TLS occurred. Conclusions: Mesutoclax in combination with orelabrutinib demonstrated a tolerable safety profile across B cell malignancy subtypes (MCL, MZL, CLL/SLL). Significant 100% ORR and deep response were observed in patients receiving mesutoclax 125mg combined with orelabrutinib. This all oral, chemo-free regimen has the potential to establish a novel therapeutic option for B-NHLs. Clinical trial information: NCT05728658 .

PURPOSE:Patients with newly diagnosed multiple myeloma (NDMM) who are ineligible for or not proceeding to autologous stem-cell transplantation (ASCT)-often because of age or frailty-have limited opportunities to receive multiple effective lines of therapy, underscoring the need for novel frontline strategies. METHODS:In this phase II, open-label, single-arm trial (ClinicalTrials.gov identifier: NCT05860036), patients received 3-4 cycles of protocol-allowed induction, followed by B-cell maturation antigen (BCMA) CAR-T infusion, and subsequent consolidation and lenalidomide maintenance. The primary end point was the rate of minimal residual disease (MRD) negativity (10-5) at Month three postinfusion. RESULTS:Between April 4, 2023, and December 26, 2024, 43 patients were screened, 40 were enrolled, and 36 received infusion (median age, 68 years [46-75]). In the infused cohort, the MRD negativity rate at Month three postinfusion was 100% (36 of 36; 95% CI, 90.3 to 100.0). With a median follow-up of 15.8 months postinfusion (range, 4.3-26.0), no MRD recurrence was observed. The complete response rate (CRR) increased from 33.3% (12 of 36; 95% CI, 18.6 to 51.0) preinfusion to 69.4% (25 of 36; 95% CI, 51.9 to 83.7) at Month 3% and 94.4% (34 of 36; 95% CI, 81.3 to 99.3) at last follow-up. The most common grade 3 to 4 adverse events were transient cytopenia, including lymphopenia (100%), neutropenia (88.9%), leukopenia (80.6%), thrombocytopenia (19.4%), and anemia (8.3%). Cytokine release syndrome occurred in 52.8% of patients (all grade 1 to 2), immune effector cell-associated neurotoxicity in 5.6% (all grade 1), and infections in 30.6% (grade ≥3 in 19.4%). No deaths or disease progressions occurred by cutoff. CONCLUSION:Frontline BCMA CAR-T therapy induces deep, rapid, and durable remissions with a manageable safety profile in the NDMM population ineligible for or not proceeding to ASCT. These findings support its investigation as a potentially practice-changing strategy for this population.

PURPOSE:Patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) face an unfavorable prognosis once first-line treatment fails; therefore, there is an unmet need for new treatment options. We evaluated the efficacy and safety of polatuzumab vedotin plus rituximab, gemcitabine, and oxaliplatin (Pola-R-GemOx) as an alternative therapy in patients with transplant-ineligible R/R DLBCL. METHODS:The phase III POLARGO trial was a randomized, open-label, global study. Following a Pola-R-GemOx safety run-in (n = 15), patients with R/R DLBCL (not otherwise specified or transformed indolent lymphoma) ineligible for autologous stem cell transplant were randomly assigned 1:1 to receive Pola-R-GemOx or R-GemOx alone every 21 days for up to eight cycles. The primary end point was overall survival (OS). RESULTS:In total, 255 patients were randomly assigned to receive Pola-R-GemOx (n = 129) or R-GemOx (n = 126). After a median follow-up of 24.6 months, patients receiving Pola-R-GemOx versus R-GemOx had a significantly lower risk of death (hazard ratio, 0.6 [95% CI, 0.43 to 0.83]; P = .0017) with a median OS of 19.5 months (95% CI, 13.3 to not estimable) versus 12.5 months (95% CI, 8.9 to 15.8). The most common grade 3/4 adverse events (AEs) were thrombocytopenia and neutropenia. Peripheral neuropathy was more common with Pola-R-GemOx (n = 73 [57%]) versus R-GemOx (n = 36 [29%]) and was primarily grade 1. Fatal AEs occurred in 15 (12%) and five (4%) patients in the Pola-R-GemOx and R-GemOx groups, respectively, and were largely driven by infections (including COVID-19). CONCLUSION:Pola-R-GemOx significantly improved OS compared with R-GemOx, offering an additional treatment option in patients with transplant-ineligible R/R DLBCL.

Minimal residual disease (MRD) negativity is a well-established prognostic marker in multiple myeloma (MM), yet the clinical relevance of MRD response timing and duration remains unclear, particularly in real-world settings. We retrospectively analyzed 1048 newly diagnosed MM patients from the National Longitudinal Cohort of Hematological Diseases in China (NICHE) between 2012 and 2023, with a total of 5406 MRD assessments. A longer time to best MRD response (> 6 months) was significantly associated with improved progression-free and overall survival, especially among those with persistent MRD positivity but stable low-level disease burden. Early responders were more likely to exhibit high tumor burden and high-risk cytogenetic abnormalities. Notably, a prolonged MRD duration (≥ 36 months) predicted favorable outcomes regardless of MRD negativity status. Integrating response timing and duration identified a "Late + Durable" MRD pattern consistently associated with the best prognosis, even in patients with persistent MRD positivity, high-risk cytogenetics, or without ASCT. These findings highlight the prognostic significance of longitudinal MRD monitoring beyond single-timepoint assessments. A slow but durable MRD response may overcome adverse biological features and support individualized risk stratification, therapeutic decisions, and long-term disease monitoring in MM.

e19571 Background: The treatment of newly diagnosed multiple myeloma (NDMM) has evolved rapidly over the past two decades. We aimed to describe temporal trends in treatment patterns and clinical outcomes among patients in China. Methods: This retrospective cohort study utilized electronic medical record data from the National Longitudinal Cohort of Hematological Diseases in China. Eligible patients were ≥18 years at diagnosis and received ≥ 4 cycles induction therapy. Patients were excluded if previously treated for MM. Patients were followed until death, study end (June 30, 2023), or last follow-up via telephone. OS and PFS were estimated by Kaplan–Meier methods. Age group stratified Cox proportional hazards regression was performed to identify prognostic factors for survival. Results: A total of 1,622 patients were included. Median age was 57.0 years, and 18.4% were aged >65 years. Most patients were male. At diagnosis, 41.8% had ISS stage III disease. IgG was the predominant subtype, and high-risk cytogenetic abnormalities were present in 24.1% of patients. Induction therapy shifted from mainly chemotherapy to proteasome inhibitor–based regimens by 2009, and to PI+IMiD-based combinations by 2019. By 2023, about 60% of patients received PI+IMiD-based induction and 30% received anti-CD38 antibody–based induction. Utilization of autologous stem cell transplantation (ASCT) also increased steadily over time, ranging from 22% to 48% annually. With median follow-up of 35.6 months, survival improved steadily over time: median PFS increased from 32.3 months (95% CI: 26.7–38.9) in 2008–2012 to 33.6 months (95% CI: 30.7–36.7) in 2013–2017, and to 48.0 months (95% CI: 44.6–52.5) in 2018–2023, while median OS rose from 78.5 months to 85.6 months to not reached. Advanced ISS stage and high-risk cytogenetics were linked to poorer clinical outcomes. In contrast, ASCT and the use of PI+IMiD-based or CD38 antibody–based induction regimens independently correlated with improved PFS and OS. Among patients aged >65 years, treatment pattern shifts were similar to those in the overall cohort, with increasing use of PI+IMiD-based and anti-CD38 antibody–based induction in recent years. Since 2016, roughly 10% of older patients received ASCT. Improvements in PFS and OS across time periods were likewise observed in this age group as well. Conclusions: Over two decades, NDMM treatment in China has transitioned from chemotherapy-based regimens to widespread use of PI+IMiD combinations and increasing use of anti-CD38 antibodies, and expanding application of ASCT. These advances have driven meaningful improvements in PFS and OS across the study period. Similar trends were observed among patients aged >65 years. Continued efforts to expand access to novel agents and optimize treatment strategies are essential to sustain and accelerate these gains.

Background:Enterococcal bloodstream infection (EBSI) carries high mortality in hematologic patients, yet no prognostic model tailored to this population exists. Methods:We retrospectively analyzed 192 hematologic patients (≥14 years) with EBSI admitted between 2014 and 2024. Clinical features, microbiology, treatment, and outcomes were assessed. Candidate predictors for 30-day mortality were selected by LASSO and entered into multivariable logistic regression. A simplified risk score was derived from regression coefficients and internally validated by bootstrap resampling. Results:The median patient age was 43 years, and acute leukemia was the predominant underlying disease (72.4%). Enterococcus faecium was the leading pathogen (71.4%), with low vancomycin resistance (1.6%). Most cases (71.9%) occurred as breakthrough infections, mainly during carbapenem therapy, and 72.9% met mucosal barrier injury laboratory-confirmed bloodstream infection criteria. The 14- and 30-day all-cause mortality rates were 13.5% and 22.4%, respectively. Independent predictors of 30-day mortality included age ≥50 years (aOR=2.29, p=0.038), severe graft-versus-host disease (aOR=6.06, p=0.003), septic shock (aOR=30.01, p<0.001). The final predictive model, incorporating these three factors along with pneumonia and high-risk hematologic disease, demonstrated optimal discrimination (AUROC 0.79, 95% CI 0.705-0.867) and calibration. A derived risk score stratified patients into low- (<2 points) and high-risk (≥2 points) groups, with markedly different 30-day mortality (11.3% vs. 39.0%, P<0.001). Conclusions:In hematologic patients, EBSIs commonly arise as breakthrough infections despite broad-spectrum antibiotic coverage, most often associated with mucosal barrier injury. Our parsimonious risk score enables early identification of patients at high risk of 30-day mortality to guide timely interventions.

Relapse and treatment resistance remain critical obstacles in the clinical management of angioimmunoblastic T-cell lymphoma (AITL), limiting the success of current therapeutic strategies. Therefore, a comprehensive characterization of the tumor microenvironment (TME) in AITL is essential to enhance treatment efficacy. This study analyzed samples from 68 patients with AITL, stratified into three molecular subtypes based on immunoglobulin (IG) gene rearrangement and flow cytometry results. Utilizing single-cell RNA sequencing, the TME was profiled across subtypes A, B, and C, sampling multiple disease sites including the bone marrow, lymph nodes, and peripheral blood. Our findings revealed subtype-specific variations in cellular composition and transcriptional programs within the TME. Unlike other subtypes, subtype C was associated with a pronounced immunosuppressive environment at diagnosis and relapse. Additionally, it exhibited an enhanced response to Epstein–Barr virus infection, consistent with upregulated CD70 expression at relapse. Through the analysis of cellular communication networks, CD70, programmed cell death 1 (PDCD1), and inducible T cell costimulator (ICOS) were identified as promising immunotherapeutic targets in AITL. Finally, we delineated distinct cellular proportions and gene expression signatures characteristic of each subtype, providing a foundation for the development of tailored therapeutic interventions for patients with AITL.

Orelabrutinib is a potent, irreversible, and highly-selective BTK inhibitor that has been approved for the treatment of relapsed/refractory chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL). This randomized, phase 3 study (ClinicalTrials.gov identifier: NCT04578613) compared orelabrutinib with chemoimmunotherapy in patients with treatment-naïve CLL/SLL. From February 20, 2021, to July 8, 2024, 192 eligible patients were randomly assigned (1:1) to receive either orelabrutinib (91 patients) or chlorambucil plus rituximab (101 patients), comprising the intention-to-treat population. At a median follow-up of 21.4 months (data cutoff, May 17, 2024), the primary endpoint of progression-free survival (PFS) per independent review committee (IRC) was not reached (NR; 95% CI, not estimable [NE]-NE) with orelabrutinib versus 19.4 months (95% CI, 16.6-NE) with chlorambucil plus rituximab (hazard ratio [HR], 0.32; 95% CI, 0.18-0.58; p < 0.0001; crossing the efficacy boundary). The IRC-assessed overall response rate (90.1% vs 79.2%; p = 0.041) and duration of response (HR, 0.30; 95% CI, 0.15-0.60; p = 0.0003) also favored orelabrutinib over chlorambucil plus rituximab. In the safety population, treatment-related adverse events occurred in 82 of 91 patients (90.1%) receiving orelabrutinib and 89 of 98 patients (90.8%) receiving chlorambucil plus rituximab, with 32 (35.2%) and 59 (60.2%) at grade 3 or worse, respectively. Orelabrutinib maintained or improved patient-reported outcomes compared with chemoimmunotherapy. In summary, orelabrutinib significantly improved PFS and response versus chemoimmunotherapy in patients with treatment-naïve CLL/SLL, with a manageable safety profile, supporting it as an effective alternative first-line option.

In this phase 2 TAI-SHAN9 study, we evaluated the safety and efficacy of birelentinib, a first-in-class oral dual inhibitor of LYN and BTK, in patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). A total of 58 patients were enrolled and received birelentinib at doses ranging from 25 to 75 mg once daily (QD). Antitumor efficacy was observed at 50 mg and above, among 42 efficacy-evaluable patients treated at 50 mg or 75 mg QD, overall objective response rate (ORR) was 47.6% (20/42) and complete response rate (CRR) was 31.0% (13/42). Responses were observed across GCB (ORR 58.3%) and non-GCB (ORR 44.8%) subtypes, as well as across the MCD-like, TP53Mut, and NOS molecular subtypes (each ORR 50.0%). At a median follow-up of 9.2 months for complete responders, the median DoR was not reached, with the longest ongoing CR exceeding 9.3 months. The grade ≥3 treatment-related adverse events included thrombocytopenia (20.7%), neutropenia (12.1%), and pneumonia (5.2%). No major bleeding, atrial fibrillation, or drug-related death was reported. These results suggest that birelentinib is a promising oral treatment for r/r DLBCL across molecular subtypes. Further clinical evaluation of LYN/BTK dual inhibition is warranted. Clinical trial information: ClinicalTrials.gov NCT06539195.

The 2025 IMS-IMWG consensus genomic staging (CGS) system has improved genomic risk stratification in newly diagnosed multiple myeloma (NDMM), yet does not capture whether high-risk clones have acquired a disseminated phenotype. We investigated whether circulating tumor cells (CTC) refine CGS and enable longitudinal residual disease monitoring. We retrospectively analyzed 631 MM patients from the NICHE cohort (NCT04645199) who underwent CTC assessment across disease phases. Among 410 patients assessed at diagnosis, CTC were detectable in 63.9% and correlated with both bone marrow plasma cell infiltration and accumulation of high-risk cytogenetic abnormalities. In 359 NDMM patients with adequate follow-up, a cohort-derived CTC threshold of 0.38% independently predicted inferior progression-free survival (PFS) after multivariable adjustment. Importantly, CTC refined prognostic stratification specifically within the CGS high-risk subgroup. Patients with CGS high-risk/CTC-high disease had the shortest PFS, thereby defining a disseminated genomic high-risk phenotype comprising 12.4% (39/314) of evaluable NDMM patients. In follow-up cohorts, detectable CTC were associated with inferior outcomes in 127 patients assessed during non-progressive disease states, whereas combined CTC and bone marrow minimal residual disease assessment stratified outcomes in 120 patients with paired measurements. Overall, CTC-integrated CGS supports minimally invasive baseline risk stratification and longitudinal disease monitoring.

Introduction: Targeted therapies have significantly transformed the management of chronic lymphocytic leukaemia (CLL), yet most recommendations continue to reflect Western practice patterns. Variations in disease biology, healthcare resources and treatment accessibility across the Asia-Pacific (APAC) necessitate region-specific guidance. The Asia-Pacific Leukaemia Consortium (APLC) therefore developed updated consensus statements to support standardised, context-appropriate care for patients with CLL. Methods: A modified Delphi process was conducted with 17 haematology experts from multiple APAC regions. A systematic literature search (i.e. MEDLINE via PubMed) covering publications from 2016 onwards informed the development of 29 statements across 3 domains: diagnosis, treatment and long-term management. Panel members rated each statement using a 5-point Likert scale. Consensus was defined a priori as a mean score ≥3.5. Statistical measures and iterative expert discussions guided refinement of the final recommendations. Results: Twenty-nine statements reached consensus with key recommendations addressing: (1) appropriate use of genetic and prognostic testing, particularly TP53 and immunoglobulin heavy chain (IGHV) status; (2) first-line and relapsed/refractory treatment selection, including the role of Bruton’s tyrosine kinase (BTK) inhibitors, B-cell lymphoma 2 inhibitors, combination strategies, cellular therapies and emerging modalities; and (3) long-term monitoring, toxicity surveillance and management of complications such as autoimmune cytopenias. Region-specific considerations—such as variable access to novel agents and diagnostic platforms—were incorporated throughout. Conclusion: These updated APLC consensus recommendations provide clinicians across the APAC with an evidence-based, pragmatic framework for managing CLL. They aim to support treatment consistency, optimise sequencing strategies and address gaps in diagnostics, access and long-term survivorship care across diverse healthcare settings.

Abstract Mantle cell lymphoma (MCL) is a biologically heterogeneous B-cell malignancy. Although genomics and transcriptomics have delineated parts of the MCL disease spectrum, proteomics remains largely unexplored. Here, we conducted a comprehensive proteogenomic analysis integrating genomics, transcriptomics, and proteomics on peripheral blood samples from 27 patients with MCL and 4 healthy donors to investigate the translational and posttranslational dimensions of MCL. Our study identified 1296 downregulated and 468 upregulated proteins in MCL cells. The splicing pathways were significantly upregulated at both the mRNA and protein levels, suggesting a critical role for aberrant RNA splicing in MCL pathogenesis. Integration of proteomic data with genetic aberrations revealed immunoglobulin heavy chain variable mutational status and CCND1 mutation are associated with distinctive transcriptomic and proteomic profiles, which correspond to significant differences in clinical outcomes. A multiomics molecular stratification model incorporating proteomic data showed superior predictive power for patient survival compared with single-omics models (concordance index, 0.83 vs 0.74). This study provides, to our knowledge, the first comprehensive proteogenomic profile of MCL, offering novel insights into its molecular mechanisms and clinical behavior. The identification of molecular subtypes and prognostic protein signatures underscores the potential of proteomics to guide precision medicine strategies for MCL.

Abstract Background: Epidemiologic and other studies have identified environmental, occupational, and genetic risk factors for lymphoid and myeloid malignancies, but most studies have been conducted in Western populations. Investigations in populations with differing exposure patterns, distributions of disease subtypes, and genetic architecture are needed to fully understand hematopoietic tumor etiology. Methods: We conducted a large, multicenter, hospital-based case-control study of lymphoid and myeloid neoplasms in East Asia (AsiaLymph), including 5,671 lymphoid cases, 1,879 myeloid cases, and 3,858 controls. Participants completed a computer-assisted personal interview and provided biospecimens. Cases underwent central pathology review and were coded into the WHO Classification. Herein, we describe the study methods in detail and report association results for education, body mass index, and family history. Results: Greater BMI at age 20 but not at age 40 was associated with odds of total lymphoid neoplasm (per 5 kg/m2 increase: OR [95% CI]: 1.18 [1.09-1.27]), total myeloid neoplasm (OR [95% CI]: 1.17 [1.05-1.29]), and several subtypes. Greater educational attainment was associated with increased odds of total lymphoid neoplasm (for college vs. less than primary education: OR [95% CI]: 1.41 [1.21-1.65]) but not myeloid neoplasm (OR [95% CI]: 1.17 [0.95-1.45]; p-heterogeneity=0.02). There were also positive associations between family history of hematologic cancer in first degree relatives and odds of lymphoid neoplasm (OR [95% CI]: 1.53 [1.15-2.03]) and myeloid neoplasm (OR [95% CI]: 1.65 [1.11-2.44]) and specific subtypes. None of the evaluated risk factors were associated with NK/T-cell lymphoma, which supports a distinct etiology for this subtype. Conclusion: The AsiaLymph Study is one of the largest molecular epidemiology studies of both lymphoid and myeloid neoplasms with standardized World Health Organization classification of histopathologic subtypes and will serve as a valuable resource for etiologic investigations into risk factors for these malignancies. Citation Format: Qing Lan, Lauren M. Hurwitz, John K. Chan, Tai Hing Lam, Kexin Chen, Yok Lam Kwong, Xu Caigang, Brian CH Chiu, Raymond Liang, Ip Dennis, Wei Hu, Bryan Bassig, Mark Purdue, Jun Xu, Sarah Locke, Sophia S. Wang, James R. Cerhan, Sonja Berndt, Jonathan N. Hofmann, Jianxin Shi, Kai Yu, Shahinaz Gadalla, Lisa J. McReynolds, Rena Jones, Hongji Dai, Zhangyan Lyu, Lugui Qiu, Wei Liu, Huilai Zhang, Xianhuo Wang, Lindsay M. Morton, Stephen Chanock, Martha Linet, Melissa C. Friesen, Roel Vermeulen, Nathaniel Rothman. A multi-center hospital-based case-control study of lymphoid and myeloid neoplasms (AsiaLymph): Study design and initial findings for education, body mass index, and family history [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5051.

This study evaluated the efficacy and safety of obinutuzumab plus bendamustine (GB) as first-line treatment for indolent B-cell lymphomas. In this prospective, multicenter, single-arm trial (NCT06415708), adults with newly diagnosed indolent B-cell lymphomas—including follicular lymphoma (FL), marginal zone lymphoma (MZL), Waldenström macroglobulinemia (WM), hairy cell leukemia variant (HCL-v), and unclassified B-cell lymphoproliferative disorder (BCLPD-U)—received six induction cycles of GB followed by 2 years of obinutuzumab maintenance in responders (⩾ partial response). The primary endpoint was overall response rate (ORR), whereas secondary endpoints included complete response rate (CRR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Among 220 enrolled patients (149 with FL and 71 with non-FL), 210 completed ⩾ 3 treatment cycles. At a median follow-up of 13.1 months, ORRs in the different patient subgroups were 96.6

OBJECTIVES:Talquetamab (G-protein-coupled receptor class C group 5 member D [GPRC5D] × CD3 bispecific antibody) demonstrated antitumor activity in relapsed/recurrent multiple myeloma (RRMM) in the phase I/II MonumenTAL-1 study. We report the safety profile of talquetamab in Chinese patients from MonumenTAL-1, focusing on GPRC5D-associated on-target/off-tumor adverse events (AEs). METHODS:Adult Chinese patients with heavily pretreated RRMM and measurable disease received subcutaneous talquetamab 0.4 mg/kg once weekly (QW) or 0.8 mg/kg biweekly (Q2W). Incidence, time to onset, duration, and recovery status of GPRC5D-associated AEs were reported. Data cutoffs: 29 February 2024 (QW cohort); 26 August 2024 (Q2W cohort). RESULTS:A total of 41 adult Chinese patients were included in this study (QW cohort, n = 29; Q2W cohort n = 12). Median treatment duration was 7.7 months (QW cohort) and 7.1 months (Q2W cohort); median follow-up was 16.3 and 13.9 months, respectively. GPRC5D on-target/off-tumor AEs, predominantly grade 1-2 (one grade 3 non-rash skin toxicity; QW cohort), were most commonly oral AEs (dysgeusia, dry mouth), skin AEs (rash, non-rash skin toxicity), and nail disorders; 50%-100% resolved by data cutoff. AEs were managed with supportive therapies. Talquetamab dose modification was needed in one case (grade 2 weight decrease). DISCUSSION:The generally mild GPRC5D-associated AEs were well tolerated and consistent with the known safety profile of talquetamab. Supportive management of these AEs without need for dose modification enabled prolonged treatment. CONCLUSIONS:Education of patients with RRMM on potential GPRC5D-associated AEs before starting treatment, and timely management upon experience, may ensure optimum exposure and thus maximum benefit with talquetamab.

To assess the effectiveness of cord blood nucleated cell extract (CBNCE) in rheumatoid arthritis (RA) and explore the mechanism preliminarily. CBNCE injection was prepared by adding HClO4 and KOH to cord blood. The efficacy of CBNCE was assessed through a lymphocyte proliferation assay. Subsequently, the CIA model was utilized as the RA model, with rats being randomly assigned to a normal group, model group, CBNCE group (1 mL/d), and HSS group (hydrocortisone sodium succinate, 0.2 mL/d). Following a 7-day period of immune system enhancement, continuous medication was administered for the subsequent 21 days. Foot swelling tests, HE staining, flow cytometry, ELISA, WB, and immunofluorescence were conducted. The average inhibitory rate of CBNCE on lymphocyte proliferation was 83.51

OBJECTIVES:Zanubrutinib demonstrated superiority to ibrutinib in the ALPINE (NCT03734016) phase 3 trial for relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma (R/R CLL/SLL). This post hoc analysis examined patient-reported outcomes (PROs) in the Chinese subgroup. METHODS:Adults with R/R CLL/SLL and ≥1 prior therapy were randomized 1:1 to zanubrutinib or ibrutinib. PROs, a secondary endpoint, were measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30. Differences between treatment arms from baseline to Cycles 7 and 13 for key PRO endpoints were assessed using a mixed model for repeated measures. Changes from baseline on the EQ visual analog scale (EQ-VAS) were examined descriptively. RESULTS:As of February 28, 2024, 90 Chinese patients were randomized to zanubrutinib (n = 47) or ibrutinib (n = 43). Global health status/quality of life improved in both arms. Fatigue was reduced in both arms, with greater improvement in the zanubrutinib versus ibrutinib arm at Cycles 7 and 13. Nausea/vomiting scores generally remained unchanged, and all other symptoms showed similar improvement in both arms. Greater improvement in health status, measured by VAS score, was observed for the zanubrutinib arm at Cycle 13 (Cycle 7, 4.8 vs 4.1; Cycle 13, 5.7 vs 1.7). CONCLUSIONS:In ALPINE, Chinese patients with R/R CLL/SLL treated with zanubrutinib showed better and faster PRO outcomes versus those treated with ibrutinib, particularly in fatigue. These results corroborate PRO findings in the intent-to-treat population and support the benefit of zanubrutinib as a valuable treatment option for Chinese patients with R/R CLL/SLL. TRIAL REGISTRATION:NCT03734016. Registered 01 November, 2018 https://clinicaltrials.gov/study/NCT03734016.