Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku - LARVOL DELTA

Venetoclax and Obinutuzumab Followed by Epcoritamab for the Treatment of Untreated Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, LonGEVity Trial (clinicaltrials.gov) - P2 | N=33 | Recruiting | Sponsor: City of Hope Medical Center | Not yet recruiting ➔ Recruiting | Trial completion date: Aug 2028 ➔ Jun 2029 | Trial primary completion date: Aug 2028 ➔ Jun 2029

Enrollment open • Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

Predictors of health-related quality of life in adults with chronic lymphocytic leukemia or small lymphocytic lymphoma (ASH 2025) - P | "All patients with pathology-confirmed diagnoses of CLL who are within 7 days of starting treatment with a BTKi +/- an anti-CD 20 monoclonal antibody or BCL2i with obinutuzumab treatment will be included...NCT 07030400. Funded by the National Comprehensive Cancer Network/Astra Zeneca"

Clinical • HEOR • Alzheimer's Disease • B Cell Lymphoma • Chronic Lymphocytic Leukemia • CNS Disorders • Dementia • Leukemia • Lymphoma • Small Lymphocytic Lymphoma • Vascular Neurology • BCL2

National practice patterns and preferences in the use of fixed-duration vs. treat-to-progression therapies for CLL (ASH 2025) - "In the R/R setting, fixed-duration preferences included venetoclax plus rituximab (39%) and venetoclax plus obinutuzumab (34%)...Among TTP strategies, first-line use of acalabrutinib (56%) and zanubrutinib (52%) was prominent in the survey, aligning with claims data that showed both agents as the most prescribed TTP therapies (28% each)... This data highlighted evolving practice patterns in the management of CLL and revealed variation in treatment preferences among academic and community-based clinicians and between survey and claims data. While adoption of genetic testing and newer therapeutic options appears high, clinicians face ongoing challenges in selecting and implementing appropriate regimens, particularly when balancing patient-centered factors with clinical efficacy and operational realities. Both fixed-duration and TTP strategies offer distinct advantages and limitations."

IO biomarker • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • IGH • TP53

Real-world discontinuation of cBTKi-based treatments in patients with CLL/SLL in the United States (ASH 2025) - "Combination with CD20 monoclonal antibody (n=550, 88.4%) was the most common, of which 55.1% (303/550) were in combination with obinutuzumab...High rates of early discontinuation of cBTKi in the real world raise the need for effective and more tolerable tx options in CLL/SLL. The interpretation of the findings is constrained by the unavailability of data on reasons for tx discontinuation and sequencing of different cBTKis."

Clinical • IO biomarker • Real-world • Real-world evidence • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Small Lymphocytic Lymphoma • IGH • TP53

A genomic analysis of patients with chronic lymphocytic leukemia treated with fixed duration therapy in a first-line setting in alberta, Canada (ASH 2025) - "For younger, fit patients with favourable-risk genetic markers such as the absence of del(17p)/ TP53 mutations and mutated IGHV, first-line (1L) chemoimmunotherapy (CIT) with fludarabine, cyclophosphamide, and rituximab (FCR) remains a reasonable option. With the emergence of targeted fixed-duration (FD) therapies, such as venetoclax plus obinutuzumab (V+O) and ibrutinib plus venetoclax (I+V), which have demonstrated superior efficacy and reduced toxicity, CIT use has declined in the 1L setting (Al-Sawaf et al., 2024; Schnaiter et al., 2024; George et al., 2025)...Among patients receiving CIT, 61 (30.5%) received FCR, 76 (38%) received bendamustine plus rituximab (BR), 26 (13%) received chlorambucil plus obinutuzumab (Clb+O), and 6 (3%) received chlorambucil plus rituximab (Clb+R)... In this chart-reviewed cohort of 200 patients, the average age at diagnosis was 65 years and 69.8% were male. 22% and 22.5% presented with Rai stage 3 or 4, respectively, at 1L therapy..."

Clinical • Genomic analysis • IO biomarker • Omic analysis • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • IGH • TP53

An international view on the current approaches to frontline chronic lymphocytic leukemia therapy (ASH 2025) - "First-Line Therapy Recommendations: CLL patients with del(17p)/TP53 mutations: For these high-risk patients, the panel strongly favoredcontinuous BTKi therapy, with second-generation BTKis (acalabrutinib, zanubrutinib) preferred due to their more favorable safety profiles...IGHV-unmutated CLL patients without del(17p)/TP53 mutations: While the majority of experts considered patient fitness for this group, recommending continuous BTKi monotherapy for frail patients and venetoclax-based combinations with either a BTKi (acalabrutinib, ibrutinib) or obinutuzumab for fit patients, some emphasized the overall suitability for targeted agents regardless of a traditional fitness assessment, focusing instead on specific comorbidities that might impact tolerability (e.g., cardiac or renal conditions)... This expert panel's insights address the evolving CLL treatment landscape and variable access to novel targeted therapies across LATAM, MEA, APAC, and Russia. It emphasizes that..."

IO biomarker • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Nephrology • IGH • TP53

Optim.AI™ 2.0: Functional precision platform for identifying effective immunotherapy combinations in DLBCL (ASH 2025) - "PBMCs were added to tumor cells at a fixed effector-to-target ratio, and Optim.AI 2.0 combinatorial drug sensitivity testing plates were applied to the co-culture system, with up to 12 FDA-approved drugs, including monoclonal antibodies (rituximab, obinutuzumab), antibody-drug conjugates (polatuzumab), bispecific antibodies (epcoritamab, glofitamab), targeted small-molecule inhibitors (venetoclax, everolimus, zanubrutinib), and cytotoxic chemotherapies (gemcitabine, oxaliplatin, cyclophosphamide, doxorubicin). This study demonstrates the feasibility of Optim.AI™ 2.0, an enhanced co-culture-based platform which provides a physiologically relevant and scalable approach to functionally evaluate immunotherapy drug sets. With further validation, Optim.AI™ 2.0 holds strong potential to support clinical decision-making and expand the use of immunotherapies in DLBCL."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Sarcoma • Solid Tumor

Efficacy and safety of obinutuzumab plus chlorambucil in treatment-naive chronic lymphocytic leukemia: A reappraisal for low-resource settings (ASH 2025) - "Despite being phased out in wealthier health systems, chlorambucil remains a relevant therapeutic option when combined with obinutuzumab—especially in regions where modern targeted therapies are unavailable. This regimen offers a viable, evidence-backed alternative for treatment-naive CLL patients in low-resource settings, with acceptable safety and efficacy profiles."

Clinical • Chronic Kidney Disease • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia

CD5-positive lymphoproliferative disorders with atypical phenotypes are associated with inferior overall survival compared to typical-phenotype chronic lymphocytic leukaemia when treated with targeted agents. (ASH 2025) - "Chemotherapy (CT) or chemoimmunotherapy (CIT) was the first line treatment in 15 (58%) and targeted treatment (TT) in 11 (42%) including bendamustine + rituximab in 6 (23%), fludarabine + cyclophosphamide + rituximab in 3 (11.5%), dexamethasone+ cyclophosphamide+ rituximab in 2 (7.7%), chlorambucil in 3 (11.5%), rituximab alone in 1 (3.8%), acalabrutinib in 6 (23%), ibrutinib in 2 (7.7%), Zanubrutinib + venetoclax (clinical trial) in1 (3.8%) and venetoclax + obinutuzumab in 2 (7.7%). Massive splenomegaly is a major feature in patients with CD5+LPD with atypical phenotype. These patients have an inferior OS outcome when treated with TT compared to CLL patients with typical phenotype."

Clinical • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Mantle Cell Lymphoma • CCND1 • CD5

Real‑world effectiveness and patient-centered outcomes of fixed‑duration vs continuous first‑line therapy in chronic lymphocytic leukemia (CLL) (ASH 2025) - "Background: The treatment landscape of chronic lymphocytic leukemia (CLL) has shifted with the adoption of targeted therapies administered either as fixed-duration ( venetoclax-obinutuzumab [VenO]) or continuous regimens ( Bruton tyrosine kinase inhibitors [BTKis]). Venetoclax-based fixed-duration regimens demonstrate strong real-world effectiveness with the added benefit of extended treatment-free intervals and favorable time-to-next-treatment outcomes, offering a patient-centered advantage over continuous BTKi therapy. These findings support the role of time-limited therapy in frontline CLL treatment algorithms and shared decision-making."

Clinical • Real-world • Real-world effectiveness • Real-world evidence • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia

Outcomes with a fixed duration combination of bruton tyrosine kinase inhibitors and venetoclax in chronic lymphocytic leukemia: A systematic review and meta-analysis (ASH 2025) - "BTK inhibitors used in the studies included ibrutinib (67%, n = 775), acalabrutinib (31%, n = 363), and pirtobrutinib (2%, n = 25). Anti-CD 20 antibody was added in 188 patients, Obinutuzumab in 163 (87%), and Rituximab in 25 (13%) patients... The fixed-duration combination of BTK inhibitors and venetoclax shows very promising response rates compared to either of these agents as monotherapy. This necessitates the continuation of high-quality trials to consolidate these findings."

IO biomarker • Retrospective data • Review • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia

Discovering the epidemiology, treatment patterns, and outcomes of chronic lymphocytic leukemia: A retrospective multicenter cohort study (ASH 2025) - "Among patients who required treatment, the most commonly used regimens were FCR (22.2%), R-CHOP (20%), R-COP (18%), R Bendamustine (15%), Obinutuzumab Venetoclax (12%), and BTK inhibitors (10%). We believe that this limitation does not allow patients to be treated according to their risks, which is why we see a high percentage of patients still receiving immunochemotherapy, which is not in accordance with international guidelines. Knowing these data allows us to increase efforts to improve access to diagnosis and targeted treatments in our country."

Retrospective data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia

BTK inhibitor (Bruton Tyrosine Kinase inhibitor) plus anti-CD20 antibody therapy surpasses CIT( chemoimmunotherapy)in frontline CLL( chronic lymphocytic leukemia) with obinutuzumab drives deeper remissions: A meta‑analysis of randomized controlled trials (ASH 2025) - "The depth of response is influenced by the choice of anti-CD20 antibody: obinutuzumab-based regimens are associated with higher complete response rates, while rituximab-based combinations tend to yield partial responses. These findings support the selection of obinutuzumab-based BTKi combinations to maximize response depth in frontline CLL treatment."

Retrospective data • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia

FCR-I/iven combination for CLL: «Cheap but fierce» (ASH 2025) - "Besides, in case of relapse, ibrutinib and venetoclax can be used as retreatment. The addition of obinutuzumab to the FC regimen is promising due to its superior results over rituximab."

IO biomarker • Chronic Lymphocytic Leukemia • IGH • NOTCH1 • RB1 • SF3B1 • TP53

A Phase II study of time-limited treatment with orelabrutinib plus bendamustine and obinutuzumab (OBG) in patients with treatment-Naïve CLL/SLL patients (ASH 2025) - "Background: FCR (fludarabine, cyclophosphamide, and rituximab) has been demonstrated to improve outcomes in previously untreated Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) CLL patients, but only for suitable patients, which limits it clinical application.Lower toxicity strategies, such as Bendamustine-Obinutuzumab or Bendamustine-Rituximab, demonstrated better tolerability but did not achieve comparable efficacy.BTK inhibitors (BTKi) are recommended for long-term therapy in CLL/SLL and time-limited treatment regimen has been hot topics. The Time-Limited Treatment of OBG regimen shows efficacy in unfit CLL/SLL patients, which achieved high rates of complete response combined with undetectable minimal residual disease. Safety analysis indicates that the OBG regimen is well-tolerated and adverse events are manageable. These findings support further investigation of the OBG regimen to optimize treatment outcomes in this patient population."

Clinical • P2 data • Atrial Fibrillation • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Herpes Zoster • Hypertension • Infectious Disease • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Small Lymphocytic Lymphoma • Thrombocytopenia • Varicella Zoster • IGH • TP53

The clinical trials landscape in chronic lymphocytic leukemia: A systematic review of control arm adequacy (ASH 2025) - "The Alliance A041202 and CLL14 trials demonstrated substantial progression-free survival (PFS) benefits of BTKi monotherapy and fixed-duration venetoclax plus obinutuzumab (Ven/Obi), respectively, establishing them as standard first-line treatments...Six trials (42.8%) employed substandard control arms, all utilizing a combination of chemoimmunotherapy: fludarabine/cytarabine/rituximab or bendamustine/rituximab (n=4) or chlorambucil and rituximab (n=2)...Notably, 2 of the BTKi trials utilized ibrutinib rather than next-generation BTKis, such as acalabrutinib or zanubrutinib... Of all modern phase III trials for treatment-naive CLL, nearly half did not utilize control arms that align with the current SOC in the US or EU, risking inflated estimates of the efficacy of their experimental therapies and compromising the external validity of their results. However, although the small sample size limited statistical analysis, we found that the majority of these trials were..."

Clinical • Review • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia

Efficacy of fixed-duration venetoclax-based regimens as first-line in chronic lymphocytic leukemia: A systematic review and meta-analysis of clinical trials (ASH 2025) - "Comparisons were drawn between ven-based regimens including doublets [Ven+Obinutuzumab (Obi), Ven+Ibrutinib (Ibr), Ven+Acalabrutinib (Acala)] and triplets (BTKi + Ven + Obi) and CIT comparators such as chlorambucil+Obi or fludarabine (Flu)-based combinations...Flu cyclophosphamide rituximab/bendamustine rituximab N=519, ORR, PFS 1 year, and PFS 2 years were given as 88% (CI 56-98%), 91% ( CI 86-94%), and 80% (CI 77-84%), respectively... Ven+Obi consistently showed superior PFS and ORR compared to CIT, positioning it as a frontline standard for time-limited therapy. While the Ven+Ibr combination offered similar durability, it introduced higher cardiovascular toxicity, requiring patient-specific consideration. The addition of a third agent did not yield meaningful clinical benefit in PFS but increased myelosuppression, underscoring the need for regimen personalization."

Retrospective data • Review • Atrial Fibrillation • Chronic Lymphocytic Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Hypertension • Leukemia • Neutropenia

First-line venetoclax-based regimens versus chemoimmunotherapy in chronic lymphocytic leukemia: A real-world analysis from the brazilian CLL registry (ASH 2025) - "Randomized trials such as CLL14 and CLL13 have demonstrated the superiority of venetoclax-obinutuzumab (VenO) over chemoimmunotherapy in both elderly and younger, fit patients...Three-year TTNT rates were: R-chlorambucil 34%, G-chlorambucil 51%, R-bendamustine 78%, FCR 67%, VenR 77%, and VenG 83%... Real-world data from this cohort allowed us to compare venetoclax-based regimens with CIT as first-line therapy for CLL, including high-risk patients. As expected, venetoclax-based regimens showed favorable results, and their use should be considered as an effective time-limited therapy, even in lower-middle-income countries. Updated analyses with longer follow-up and broader inclusion will be presented at the meeting."

Clinical • IO biomarker • Real-world • Real-world evidence • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • B2M • TP53

Oncogeriatric assessment of patients with chronic lymphatic leukaemia over 65 years old undergoing target therapies: A pilot study conducted at the fondazione policlinico gemelli. (ASH 2025) - "Treatments included ibrutinib (6), acalabrutinib (13), zanubrutinib (5), venetoclax (4), venetoclax - obinutuzumab (2), and venetoclax - rituximab (2). During the study period, 39 CLL pts were enrolled (28 males and 11 females), with a median age of 75 years (70-80). Concerning biological features, IGHV was unmutated in 16/26 (60%) pts. Del17 was present in 3/28 (11%)."

Clinical • IO biomarker • Atrial Fibrillation • Cardiomyopathy • Chronic Lymphocytic Leukemia • Congestive Heart Failure • Diabetes • Diabetic Nephropathy • Heart Failure • Hematological Malignancies • Hypertension • Leukemia • Metabolic Disorders • Renal Disease • TP53

Immune reconstitution after venetoclax-based treatments in CLL (ASH 2025) - "We assessed improvement in immunoglobulin levels after different Ven-based treatments, including Ven monotherapy, combinations with rituximab or obinutuzumab (Ven + O), and combination with ibrutinib (Ven + I). Our findings support that humoral immune reconstitution can be achieved after Ven-based treatment, based on recovery of IgA levels. IgA levels improved after Ven + CD20 therapy, as per prior reports, though Ven + CD20 mAb resulted in more significant initial reduction in IgA levels than Ven monotherapy or Ven + I. Interestingly, we did not find an association between superior IgA increases and depth of response."

Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia

Glofitamab combined with salvage therapy for relapsed or refractory aggressive B-cell lymphomas: Efficacy and safety in a real-world prospective observational study (ASH 2025) - P | "Pretreatment included obinutuzumab 1000mg (Cycle 1 Day 1), followed by glofitamab step-up dosing (2.5mg C1D8, 10mg C1D15, 30mg from C2D1). This real-world study demonstrates favorable efficacy and manageable safety of glofitamab-based salvage therapy in R/R aggressive B-cell lymphomas. Combination therapy significantly improved outcomes, with no regimen-dependent differences observed. CRS and infections require vigilant monitoring, but the regimen offers a promising therapeutic option for this refractory population."

Clinical • IO biomarker • Observational data • Real-world • Real-world evidence • B Cell Lymphoma • Burkitt Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • High-grade B-cell lymphoma • Infectious Disease • Lymphoma • Marginal Zone Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Richter's Syndrome • BCL2 • CD20 • MYC

Efficacy, safety, and T-cell population dynamics of glofitamab monotherapy in relapsed/refractory B-cell lymphoma (ASH 2025) - "Patients and methods All patients with R/R BCL received a single dose of obinutuzumab pretreatment (1,000 mg) 7 days before the first cycle of glofitamab. After two cycles therapy, the incidence of CRS and the level of IL-6 decreased significantly. It is very interesting that T-cell exhaustion in the early stage of treatment might be associated with better therapeutic effects."

Clinical • Monotherapy • B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Thrombocytopenia • CD4 • CD8 • IL6

Favorable Outcomes of Bridging Glofitamab Prior to anti-CD19 CAR-T cell Therapy in patients with non-Hodgkin lymphoma (ASH 2025) - " Pts with R/R NHL who underwent leukapheresis received pre-treatment with obinutuzumab prior to the first dose of glofitamab. Based on disease progression status, pts received glofitamab monotherapy or glofitamab combined with gemcitabine + oxaliplatin/ BTK inhibitor/ methotrexate regimens prior to CAR-T infusion... Glofitamab bridging therapy prior to CAR-T demonstrated promising efficacy in pts with high-risk NHL, without significant safety concerns or detrimental impact on CAR-T cell kinetics. This study provides preliminary evidence for redefining therapeutic paradigms in non-Hodgkin lymphoma, particularly PCNSL, supporting further investigation through expanded validation cohorts and longitudinal outcomes assessment."

CAR T-Cell Therapy • Clinical • IO biomarker • B Cell Lymphoma • Bone Marrow Transplantation • Burkitt Lymphoma • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Infectious Disease • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma • TP53

Safety and efficacy of glofitamab in combination with lenalidomide in relapsed or refractory central nervous system lymphoma: Real-world data (ASH 2025) - "Pretreatment with obinutuzumab (1000 mg) was administered intravenously 7 days before the first dose of glofitamab. Glofitamab was then administered intravenously by step-up dosing during cycle 1 (day 8: 2.5 mg; day 15: 10 mg), followed by fixed-dose glofitamab 30 mg on day 1 of cycles 2~12 To mitigate the risk of cytokine release syndrome (CRS), patients received premedication (dexamethasone 20mg intravenously, acetaminophen 1000mg orally, isopropanazine 25mg intramuscularly) 1 hour before glofitamab therapy... The cohort comprised one male and three females, with a mean age of 58 years (range: 51~69). Median time to relapse after last treatment was 5 months (range: 3~8). Relapse symptoms included neurological symptoms (such as headache, lethargy, limb weakness, gait disturbance, slurred speech, visual deficits, etc.) and systemic symptoms (such as nausea, anorexia, fatigue, etc.) After two cycles of treatment, all patients achieved rapid remission (two complete..."

Clinical • Combination therapy • Real-world • Real-world evidence • Anorexia • B Cell Lymphoma • Brain Cancer • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Solid Tumor • CD20

Pharmacokinetic failure of obinutuzumab due to massive third-space sequestration in a patient with high-burden follicular lymphoma: A rationale for therapeutic drug monitoring and dose intensification (ASH 2025) - "This case highlights a critical and underappreciated mechanism of treatment failure in high-burden lymphoma: pharmacokinetic failure due to dual impact of high tumor burden and massive third-space drug sequestration. The resulting subtherapeutic systemic exposure led to poor clinical response that could have been misclassified as primary drug resistance. Our findings underscore the necessity of recognizing the "pharmacokinetic sink" effect in patients with significant serous effusions."

Clinical • PK/PD data • B Cell Non-Hodgkin Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Pulmonary Disease • Respiratory Diseases • B2M