zuberitamab

ABSTRACT The ‘Antibodies to Watch’ article series provides an annual summary of commercially sponsored monoclonal antibody therapeutics currently in late-stage clinical development, regulatory review, and those recently granted a first approval in any country. In this installment, we discuss key details for 16 antibody therapeutics granted a first approval in 2023, as of November 17 (lecanemab (Leqembi), rozanolixizumab (RYSTIGGO), pozelimab (VEOPOZ), mirikizumab (Omvoh), talquetamab (Talvey), elranatamab (Elrexfio), epcoritamab (EPKINLY), glofitamab (COLUMVI), retifanlimab (Zynyz), concizumab (Alhemo), lebrikizumab (EBGLYSS), tafolecimab (SINTBILO), narlumosbart (Jinlitai), zuberitamab (Enrexib), adebrelimab (Arelili), and divozilimab (Ivlizi)). We briefly review 26 product candidates for which marketing applications are under consideration in at least one country or region, and 23 investigational antibody therapeutics that are forecast to enter regulatory review by the end of 2024 based on company disclosures. These nearly 50 product candidates include numerous innovative bispecific antibodies, such as odronextamab, ivonescimab, linvoseltamab, zenocutuzumab, and erfonrilimab, and antibody–drug conjugates, such as trastuzumab botidotin, patritumab deruxtecan, datopotamab deruxtecan, and MRG002, as well as a mixture of two immunocytokines (bifikafusp alfa and onfekafusp alfa). We also discuss clinical phase transition and overall approval success rates for antibody therapeutics, which are crucial to the biopharmaceutical industry because these rates inform decisions about resource allocation. Our analyses indicate that these molecules have approval success rates in the range of 14–32%, with higher rates associated with antibodies developed for non-cancer indications. Overall, our data suggest that antibody therapeutic development efforts by the biopharmaceutical industry are robust and increasingly successful.

Research Background B lymphocyte-mediated adaptive immunity is pivotal in the pathogenesis of membranous nephropathy (MN). This study evaluated the efficacy and safety of zuberitamab, a novel anti-CD20 monoclonal antibody, in primary membranous nephropathy (PMN). Research Methods We retrospectively analyzed 25 patients with PMN treated with zuberitamab (zuberitamab group). Using 1:1 propensity score matching, we selected a comparable control cohort of 25 PMN patients who received rituximab during the same period (RTX group). The primary endpoint was the 12-month overall remission rate (CR + PR). Research Results All 25 patients (100.0%) in the zuberitamab group achieved clinical remission (CR 80.0%) at 12-month, with 11 patients achieving complete immunological remission. Compared to the RTX group, the complete remission (CR) rate was significantly higher (80.0% vs 32.0%, P<0.01). Kaplan-Meier analysis demonstrated a higher complete remission rate (log-rank P<0.001; HR = 4.187, 95% CI [2.285-7.672]). Zuberitamab induced progressive urine protein-to-creatinine ratio (uPCR) reduction (all P<0.001) and sustained albumin improvement (3-month: P<0.05; 6/9/12-month: P<0.001). Peripheral blood CD19+ B-cell counts decreased to < 5 cells/μl at 6-month among the 22 patients with complete follow-up data, and remained consistently low throughout follow-up. No severe adverse events were observed in either group. Conclusion Zuberitamab may be a promising treatment option for PMN, demonstrating a high complete remission rate and sustained proteinuria reduction in this study. Large-scale prospective studies are warranted to confirm these findings.

Rationale & Objective Idiopathic membranous nephropathy (IMN) is a major cause of nephrotic syndrome. Although rituximab has improved outcomes, resistance or intolerance occurs in a subset of patients. Zuberitamab, a chimeric anti-CD20 immunoglobulin G1 monoclonal antibody, may offer an alternative therapeutic option. This study aimed to evaluate the effectiveness and safety of zuberitamab in patients with phospholipase A2 receptor (PLA2R)–associated IMN. Study Design Single-center, retrospective observational cohort study. Setting & Participants Sixty patients with biopsy-proven or serologically diagnosed PLA2R-associated IMN were treated with zuberitamab at Henan Provincial People’s Hospital between July 2023 and June 2024. Thirty-five received zuberitamab as first-line therapy; 25 received it as second-line therapy following prior immunosuppressive treatment. Intervention(s) Zuberitamab infusions administered in 2-3 doses over several months, guided by B-cell kinetics. Outcomes The primary outcome was complete or partial remission of proteinuria at 3 and 6 months. Secondary outcomes included changes in serum albumin, serum creatinine, estimated glomerular filtration rate, CD19+ B cells, and anti-PLA2R antibody titers. Results At month 3, 80% (48/60) of patients achieved remission (5 complete and 43 partial). By month 6, 13 patients achieved complete remission (11 first line and 2 second line; P = 0.03), and 35 achieved partial remission. Serum albumin levels improved, whereas proteinuria and creatinine levels declined in both groups. At 6 months, PLA2R antibody < 2 RU/mL was seen in 90.9% (30/33) of first-line and 81.0% (17/21) of second-line patients (P = 0.29). No serious adverse events were observed. Limitations Single-center, retrospective design; short follow-up; no direct comparator group; incomplete biomarker data owing to testing limitations. Conclusions Zuberitamab was associated with favorable clinical and immunologic responses in patients with IMN, including those previously treated with rituximab. These findings support its potential role as a therapeutic option, warranting further validation in prospective studies.

Background In patients with untreated CD20-positive diffuse large B-cell lymphoma (DLBCL), a phase 3 trial was carried out to evaluate the efficacy and safety of zuberitamab plus CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone; Hi-CHOP) versus rituximab plus CHOP (R-CHOP) treatment regimens. Methods In a 2:1 ratio, eligible patients were assigned randomly to receive treatment of six cycles of either 375 mg/m2 zuberitamab or rituximab together with conventional CHOP chemotherapy. The objective response rate (ORR) at C6D50 served as the primary endpoint, and a non-inferiority margin of 10% was established. The secondary endpoints included the complete response (CR) rate at C6D50, duration of response (DOR), progression-free survival (PFS) and event-free survival (EFS) judged by blinded-independent review committee (BIRC), overall survival (OS) and safety outcomes. Results Of the 487 randomized patients, 423 patients including 287 in the Hi-CHOP and 136 in the R-CHOP groups completed the C6D50 assessment. For the full analysis set (FAS) and per-protocol set (PPS), BIRC-assessed ORR at C6D50 for the Hi-CHOP and R-CHOP groups were 83.5% versus 81.4% and 95.3% versus 93.7%, respectively. The non-inferiority was confirmed as the lower limit of the two-sided 95% CI for the intergroup differences of −5.2% and −3.3%; both were >−10% in the FAS and PPS. The BIRC-assessed CR rate of Hi-CHOP was significantly higher in PPS (85.7% vs 77.3%, p=0.038), but comparable in FAS (75.2% vs 67.9%, p=0.092). After a median follow-up of 29.6 months, patients in the Hi-CHOP group had a slight advantage with regard to the DOR (HR 0.74, p=0.173), PFS (HR 0.67, p=0.057), EFS (HR 0.90, p=0.517) and OS (HR 0.60, p=0.059). Patients with the germinal-center B cell-like subtype who received Hi-CHOP exhibited statistically significant improvements in ORR (p=0.034) and CR rate (p=0.038) at C6D50, EFS (p=0.046) and OS (p=0.014). Treatment-emergent adverse event occurrence rates were comparable across groups (all p>0.05). Infusion-related responses occurred more often in the Hi-CHOP group (32.1% vs 19.9%, p=0.006), all of grade 1–3 severity. Conclusions Zuberitamab (375 mg/m2) plus CHOP was non-inferior to R-CHOP regarding ORR but exhibited a higher CR rate and was well tolerated in CD20-positive, previously untreated Chinese patients with DLBCL. Trial registration number Chinese Clinical Trial Registry, ChiCTR2000040602, retrospectively registered.

Purpose To conduct a cost-effectiveness analysis comparing zuberitamab combined with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone; Hi-CHOP) versus rituximab combined with CHOP (R-CHOP) as first-line therapy for previously untreated CD20-positive diffuse large B-cell lymphoma (DLBCL) patients in China. Patients and Methods A partitioned survival model (PSM) was developed to conduct a cost-effectiveness analysis of Hi-CHOP versus R-CHOP regimens in newly diagnosed CD20-positive DLBCL patients. The study utilized a 20-year time frame. Evaluated outcomes included overall survival (OS), quality-adjusted life-years (QALYs), total treatment costs, and incremental cost-effectiveness ratios (ICERs). The willingness-to-pay (WTP) threshold was defined as $40,334.05 per QALY, equivalent to triple China’s 2024 per capita GDP. Results The base-case analysis indicated that Hi-CHOP provided an additional 1.49 life-years and 1.57 QALYs compared to R-CHOP. The total treatment cost of Hi-CHOP was $238,164.77 higher than that of R-CHOP over 20 years, resulting in ICERs of $151,373.19 per QALY and $160,273.99 per life-year. One-way sensitivity analysis (OSA) identified progression-free survival (PFS) utility as the most significant parameter impacting model outcomes. Probabilistic sensitivity analysis (PSA) demonstrated that almost all simulated outcomes surpassed the WTP threshold. The cost-effectiveness acceptability curve (CEAC) demonstrated R-CHOP’s superior cost-effectiveness probability relative to Hi-CHOP across a WTP range from $0 to $150,000. Conclusion Given that Hi-CHOP is not cost-effective at conventional WTP thresholds, a substantial price reduction or unnecessary procedures, and optimizing clinical workflows for Hi-CHOP would be necessary to make it an economically viable first-line option for DLBCL compared to R-CHOP.

… zuberitamab are scarce. This study aims to evaluate the real-world effectiveness and safety of zuberitamab … MN and administered treatment with zuberitamab between June 2023 and …

Primary thyroid diffuse large B-cell lymphoma (DLBCL) represents a rare and diagnostically challenging malignancy, particularly when arising in the setting of pre-existing Hashimoto's thyroiditis (HT). The present case report describes the case of an 86-year-old female patient with primary thyroid lymphoma (PTL) who presented with life-threatening tracheal compression. The aim of this report is to emphasize the diagnostic challenges due to overlapping clinical features with thyroid carcinoma and the absence of consensus management guidelines. Following ultrasound-guided biopsy and immunohistochemical analysis, germinal center-originated DLBCL was confirmed. The patient received four cycles of zuberitamab (a novel anti-CD20 monoclonal antibody) plus mini-CHOP therapy, with CT imaging demonstrating notable tracheal re-expansion after the first cycle. Successful disease control and quality of life were maintained throughout the follow-up. Furthermore, a comprehensive literature review was performed to elucidate the clinical manifestations and therapeutic approaches of PTL. In conclusion, the present case exemplifies that elderly patients with rapidly enlarging neck masses require urgent evaluation to distinguish between thyroid lymphoma and carcinoma. While individual case results cannot be generalized to all clinical scenarios, prompt diagnosis followed by appropriate treatment remains critical for favorable outcomes

For monoclonal antibody (mAb) drugs, the 'me-too' drug is a pharmacologically active compound that is structurally similar to the first-in-class drugs, acting on the same target and is used for the same therapeutic purposes, but it may differ in drug-drug interactions and adverse drug reactions. Capillary electrophoresis-sodium dodecyl sulfate (CE-SDS) has been widely used for quality evaluation of mAb drugs. The properties of the detected substances can interfere with the credibility and accuracy of the method. In the routine comparison analysis for both innovator rituximab and 'me-too' drug zuberitamab samples, an uncommon artifact related to the heavy chain (HC) of zuberitamab was observed in reducing CE-SDS and interfered with our identification of the purity of samples. In this work, the overall hydrophobicity of the HCs of rituximab, zuberitamab, and several other common mAbs was characterized and determined by reversed-phase high-performance liquid chromatography. Additionally, the local hydrophobicity and surface charge were compared using Expasy ProtScale and PyMOL software simulations. We concluded that noncovalent protein aggregation can be related to strong hydrophobicity and low electrostatic repulsion of local amino acid regions, which complicates drug quality control. These findings shed light on the relationship between protein aggregation and the local hydrophobicity region, and broaden the way to analyze the detection 'artifacts' in reducing CE-SDS studies of therapeutic proteins.

The pathogenesis of autoimmune hemolytic anemia (AIHA) remains incompletely understood, typically associated with immune dysfunction and the production of autoantibodies. Zuberitamab, a novel anti-CD20 monoclonal antibody, represents an important therapeutic strategy for managing autoimmune diseases. Here, we present the first case of a patient diagnosed with AIHA who developed severe immunosuppression, lymphopenia, and B-cell depletion following zuberitamab treatment, ultimately resulting in severe Pneumocystis jirovecii pneumonia(PJP). This case highlights the complexities of B-cell-targeted immunotherapy and underscores the necessity of close monitoring of immune status in patients receiving zuberitamab or other targeted immunotherapies to mitigate the risk of severe immune-related adverse events.

… Zuberitamab, a humanized antiCD20 monoclonal antibody, … safety of orelabrutinib‐zuberitamab combination therapy in … for up to 12 cycles; zuberitamab is administered every 2 cycles (…

Background Diffuse Large B-Cell Lymphoma (DLBCL) represents the most prevalent subtype of Non-Hodgkin Lymphoma (NHL). Cryoglobulinemia results from reversible precipitation of serum immunoglobulin complexes at low temperatures, with Type II (mixed) cryoglobulinemia commonly associated with hepatitis C virus (HCV) infection, autoimmune diseases, and B-cell lymphoproliferative disorders. However, its occurrence secondary to DLBCL is exceedingly rare. This report presents a rare case of DLBCL complicated by Type II cryoglobulinemia, acute liver injury, acute kidney injury, and severe infection. Case report A female patient in her 40s presented to an external hospital with unexplained high fever, dry cough, and chest tightness. She was diagnosed with DLBCL based on bone marrow cytology and histopathological findings. The patient received chemotherapy with the zuberitamab plus CHOP regimen. However, anaphylactic shock occurred during zuberitamab infusion, leading to temporary discontinuation of chemotherapy. Upon transfer to our hospital, laboratory tests indicated renal insufficiency and severe hepatic injury. Combined with clinical manifestations such as extensive skin and mucosal ecchymoses, bilateral lower limb edema, arthralgia, reversible serum cryoprecipitation, positive mixed type II cryoglobulin, and decreased C4 complement levels, a diagnosis of type II cryoglobulinemia was confirmed. Following fluid resuscitation, diuresis, and continuous renal replacement therapy, her condition temporarily improved. Unfortunately, the patient succumbed due to disease progression of lymphoma. Conclusion This case illustrates the diagnostic and therapeutic management of type II cryoglobulinemia secondary to DLBCL. It highlights the importance of closely monitoring clinical manifestations and implementing early intervention for related complications during the treatment of B-cell lymphoproliferative disorders, aiming to reduce the high mortality rate and improve patient outcomes.

According to the official website of China’s National Medicines and Pharmaceutical Administration (NMPA), a total of 87 novel drugs were approved in China in 2023, with targeted …

Background: Marginal zone lymphoma (MZL) is the second most prevalent form of indolent lymphoma and the optimal strategy for symptomatic, advanced MZL is CD20-based monoclonal therapy. Orelabrutinib, a novel and irreversible Bruton's tyrosine kinase (BTK) inhibitor, exhibited a high overall response rate of 58.9% in relapsed/refractory (r/r) MZL patients. The combination of Orelabrutinib with anti-CD20 monoclonal antibody has been shown to preserve natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) and in vitro studies demonstrated that the combination of the two drugs enhanced tumor cell apoptosis. The overall response rate (ORR) reached 90% in a small sample study of MZL treated with the combination of Orelabrutinib and rituximab. The presence of minimal residual disease (MRD) has been correlated with patient prognosis, with negative MRD status linked to improved survival. This study aims to evaluate the efficacy and remission depth of a regimen combining Orelabrutinib with CD20 monoclonal antibodies, with a focus on guiding treatment discontinuation based on ultra-minimal residual disease (uMRD) and complete response (CR) criteria. Methods: This study employed a single-arm, multicenter, retrospective design. Patients diagnosed with MZL were enrolled from two clinical centers. The treatment protocol involved initial therapy with anti-CD20 monoclonal antibodies (rituximab, obinutuzumab, and zuberitamab), with or without bendamustine to control the tumor load. Subsequently, patients received a combination of Orelabrutinib and anti-CD20 monoclonal antibodies, with or without bendamustine, and continued Orelabrutinib as monotherapy maintenance. The main clinical outcomes included ORR, CR, and the rate of uMRD negativity at the conclusion of combination therapy, as well as adverse events, progression-free survival (PFS), and overall survival (OS). Results: From August 2023 to July 2024, a total of 12 eligible patients were accrued at two centers. The median patient age was 58.5 years (range 29-79), with an equal gender distribution (6 males and 6 females). 33.3%（4/12） patients were refractory recurrence and 66.7%（8/12） patients were initial treatment .Mucosa-associated lymphoid tissue (MALT) lymphoma constituted 72.7% (8/12), nodal MZL (NMZL) 9.1% (1/12), and splenic MZL (SMZL) 18.2% (2/12). Disease sites predominantly included lymph nodes, the gastrointestinal tract, spleen, abdominal cavity, lung, parotid gland, bone, and eye. According to the Lugano stage, 58.3% (7/12) of patients were staged as IV, with two patients exhibiting bone marrow involvement. MRD was detected by next-generation sequencing (NGS) in 3 patients, and MRD reached 28×102 in 1 patient. Of the 12 patients, 66.7% (8/12) received anti-CD20 monoclonal antibody monotherapy, while 33.3% (4/12) were treated with a combination of anti-CD20 monoclonal antibodies and bendamustine, and combined therapy with Orelabrutinib after tumor control for a total of 6 cycles. Orelabrutinib monotherapy was continued after the end of combination therapy for maintance. The median follow-up duration was 4.5 months. Among the seven evaluable patients, the best CR and ORR were 42.5% (3/7) and 71.4% (5/7), respectively. No significant adverse events (AEs) led to drug discontinuation or dose reduction, with AEs including bone marrow suppression, herpes zoster, sleep disturbances, gastrointestinal disorders, and fever. Conclusion: The combination of Orelabrutinib with anti-CD20 monoclonal antibodies, with or without bendamustine, has demonstrated promising efficacy and safety in the treatment of MZL. The follow-up time of this study is short, and the dynamic changes of MRD will be updated later, and the timing of drug withdrawal will be monitored by uMRD and CR.

… ZUBERITAMAB Zuberitamab (HS006) is a novel chimeric anti-CD20 monoclonal antibody that induces B… treated with zuberitamab and a matched rituximab control cohort, treatment with …

… ripatuximab, and the humanized form zuberitamab, are widely used for primary MN. They … However, whether anti-CD20 monoclonal antibody therapy has comparable effectiveness in …

Background Targeted therapy-based induction regimens provide novel treatment options for newly diagnosed mantle cell lymphoma (MCL). Recent studies have demonstrated the promising efficacy of triple-drug combinations comprising BCL-2 inhibitors, BTK inhibitors, and CD20 monoclonal antibodies (e.g., IVO, IVR, AVO, ZVO). Sonrotoclax (BGB-11417), a next-generation BCL-2 inhibitor, exhibits higher selectivity and pharmacological potency than venetoclax, with a shorter half-life and no drug accumulation. Zanubrutinib, a next-generation BTK inhibitor, has shown favorable safety and efficacy profiles in treatment-naïve (TN) MCL patients. Objective To evaluate the efficacy and safety of sonrotoclax-containing, chemotherapy-free triplet induction therapy in TN MCL. Methods This open-label, single-arm, multicenter trial (NCT06463691) enrolled treatment-naïve MCL patients. Patients received zanubrutinib (160 mg BID) plus zuberitamab, a novel CD20mab with enhanced antibody-dependent cellulal cytotoxicity, for 2 cycles as lead-in treatment. Sonrotoclax was added at Cycle 3 Day 1 with dose escalation to target 320 mg daily. Triplet therapy continued through Cycle 12. After induction, patients achieving complete remission (CR) with undetectable minimal residual disease (MRD) without high-risk features would receive 1 year of sonrotoclax plus zanubrutinib, followed by 1 year of zanubrutinib monotherapy. Patients assessed as partial response (PR), or MRD-positive, or with high-risk, and who in the judgment of the investigator, are frail or intolerant of transplantation or intensive chemotherapy, would receive the same maintenance therapy as CR patients. Others would receive R-DHAP consolidation (4 cycles), with transplant eligibility assessed per investigator, followed by zanubrutinib maintenance. High-risk features were defined as blastoid histology, Ki-67 ≥30%, TP53 aberration, and simplified MIPI score >6. Patients who meet any one of the features are considered high risk. The primary endpoint was the CR rate after triplet induction. Secondary endpoints included ORR, PFS, OS, MRD negative rate, and safety. And at the end of Cycle 6, patients received an evaluation by CT to assess the efficacy of the triplet regimen. Results At the data cutoff (June 27, 2025), 30 patients were enrolled (median age 62 years [range 42-88]; 80% male). 86.7% (26/30) of patients had stage III/IV disease, and 76.7% (23/30) had extranodal involvement. Twenty patients were high-risk: 80% (16/20) had high Ki-67, 60% (12/20) had elevated as high MIPI scores, and among the TP53 evaluable patients, 5% (1/20) had TP53 aberrations. At baseline, among the 24 patients who underwent MRD assessment, with both bone marrow and peripheral blood samples testing positive. Twenty-eight patients initiated treatment: 4 in the lead-in phase, and 24 received sonrotoclax (13 patients have completed dose escalation to 320mg). At Cycle 6, among 10 evaluable patients (by CT), 8 patients showed CR, 1 patient achieved PR, and 1 patient experienced disease progression after lead-in treatment. Among these, MRD results were available for 3 patients, all achieving undetectable MRD(uMRD) status. With a median duration of treatment of 4.3 months (range, 1.5-11), treatment-related serious adverse events occurred in 2 patients (1 thrombocytopenia and 1 upper-gastrointestinal haemorrhage). No clinical or laboratory tumor lysis syndrome, atrial fibrillation/flutter, or additional sonrotoclax-related safety signals were observed. Conclusions The preliminary results indicate sonrotoclax combined with zanubrutinb and zuberitamab showed promising efficacy, with manageable toxicity and tolerability. The study is ongoing, and further results and details will be updated.

… trials are prospective clinical studies investigating various CD20 monoclonal antibodies. Thus, we stand at the forefront of clinical trials … This study provides evidence that Zuberitamab …

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.

To evaluate the efficacy and safety of the zuberitamab, cyclophosphamide, vincristine, doxorubicin, and prednisone (Hi-CHOP) regimen in the treatment of newly diagnosed diffuse …

… B-cell lymphoma-2 (later referred to as B-cell lymphoma/ … with sonrotoclax + zanubrutinib + zuberitamab (an anti-CD20 … cycles of zanubrutinib + zuberitamab. Sonrotoclax was added …

… Additionally, four patients received 179 instead pre-treatment with zuberitamab and one with rituximab. SCNSL patients exhibited a higher proportion of elevated baseline serum lactate …

… , methotrexate, azathioprine, cyclosporine, mycophenolate for rheumatoid arthritis or inflammatory bowel disease), human … Ripertamab and Zuberitamab are structurally optimized novel …