Brukinsa (zanubrutinib) / BeOne Medicines, Medison - LARVOL DELTA

Cases and Conversations: Sequencing Strategies in Relapsed and Refractory CLL (ASH 2026) - "Pivotal phase 3 readouts — AMPLIFY (acalabrutinib + venetoclax ± obinutuzumab), CLL17, BRUIN CLL-313/-314 (pirtobrutinib), CELESTIAL-TN (sonrotoclax + zanubrutinib), and MAJIC — have reshaped both the treatment armamentarium and the decision framework around fixed-duration vs continuous therapy. Real-world data show persistent gaps in molecular testing, treatment selection, and toxicity management. This Medical Crossfire® session uses focused didactic primers paired with moderated expert debate to examine the frontline decision points clinicians face every day, with attention to molecular testing, fixed-duration vs continuous therapy, MRD-guided approaches, and proactive AE management."

Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia

CELESTIAL-TNCLL: An ongoing, open-label, multiregional, phase 3 study of sonrotoclax (BGB-11417) + zanubrutinib vs venetoclax + obinutuzumab for treatment-naïve (TN) CLL. (ASCO 2024) - P3 | "Background: The combination of venetoclax (ven), the first-generation BCL2 inhibitor, and ibrutinib, a BTK inhibitor, has demonstrated efficacy in patients with CLL (Wierda et al. Other secondary endpoints include PFS as assessed by investigator (INV); CRR by INV; rate of uMRD4 based on flow cytometry; overall response rate by IRC and INV; duration of response by IRC and INV; patient-reported outcomes; and safety and tolerability. Recruitment is ongoing."

Clinical • IO biomarker • P3 data • Chronic Lymphocytic Leukemia • Hematological Disorders • Neutropenia • TP53

Preliminary Safety and Efficacy from a Multicenter, Investigator-Initiated Phase II Study in Untreated TP53 Mutant Mantle Cell Lymphoma with Zanubrutinib, Obinutuzumab, and Venetoclax (BOVen) (ASH 2021) - P2 | "Obinutuzumab, ibrutinib, and venetoclax has been shown to be well tolerated and associated with high response rates in relapsed and untreated MCL patients (Le Gouill Blood 2021). BOVen was well tolerated in untreated TP53 mutant MCL. The preliminary efficacy is promising in this high-risk subset of MCL, however, follow-up is limited. Updated response data, including minimal residual disease assessment using a next-generation immunosequencing (IS) assay, will be presented at the meeting."

Clinical • IO biomarker • P2 data • Hematological Disorders • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Neutropenia • Oncology • Thrombocytopenia • CARD11 • SMARCA4 • TP53

ZANUBRUTINIB + OBINUTUZUMAB (ZO) VS OBINUTUZUMAB (O) MONOTHERAPY IN PATIENTS (PTS) WITH RELAPSED OR REFRACTORY (R/R) FOLLICULAR LYMPHOMA (FL): PRIMARY ANALYSIS OF THE PHASE 2 RANDOMIZED ROSEWOOD TRIAL (EHA 2022) - P2 | "Proportion of pts refractory to rituximab, refractory to the most recent line of therapy, or with PD within 24 mo of initiation of first-line therapy was 54%, 32%, and 35% with ZO and 50%, 40%, and 42% with O, respectively. Conclusion ZO demonstrated superior efficacy to O in treatment of pts with R/R FL. ZO had a favorable benefit-risk profile and represents a potential combination therapy for pts with R/R FL."

Clinical • Monotherapy • P2 data • Atrial Fibrillation • Cardiovascular • Constipation • Cough • Fatigue • Follicular Lymphoma • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Neutropenia • Oncology • Pulmonary Disease • Respiratory Diseases • Thrombocytopenia

COMBINED PIRTOBRUTINIB, VENETOCLAX, AND OBINUTUZUMAB IN FIRST-LINE TREATMENT OF PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL): A PHASE 2 TRIAL (EHA 2024) - P2 | "Background: Treatment with combined covalent BTK-inhibitor (cBTKi such as ibrutinib, acalabrutinib, zanubrutinib) withBCL2-inhibitor, venetoclax +/- CD20 monoclonal antibody obinutuzumab showed high rates of undetectableMRD (U-MRD) remission in patients (pts) with CLL (Jain, NEJM 2019; Munir NEJM 2023; Wierda, JCO 2021; Kater, NEJM Evidence 2022). We report the first results for first-line combined pirtobrutinib, venetoclax, and obinutuzumab in pts with CLL. Avery high rate of bone marrow U-MRD at 10-6 sensitivity was noted at 6-months of combined treatment. Adverse event profile was similar to what was noted in previous studies with these agents."

Clinical • P2 data • Chronic Lymphocytic Leukemia • Febrile Neutropenia • Head and Neck Cancer • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Solid Tumor • Thrombocytopenia • TP53

Zanubrutinib, Obinutuzumab, and Venetoclax for First-Line Treatment of Mantle Cell Lymphoma with a TP53 Mutation. (PubMed, Blood) - P2 | "These data support its use and further evaluation of the BOVen regimen in this high-risk population. NCT03824483."

IO biomarker • Journal • Hematological Disorders • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Neutropenia • Oncology • TP53

A Study of Zanubrutinib, Obinutuzumab, and Sonrotoclax in People With Mantle Cell Lymphoma (clinicaltrials.gov) - P2 | N=45 | Not yet recruiting | Sponsor: Memorial Sloan Kettering Cancer Center

New P2 trial • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • Transplantation • CD4

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

Combined Pirtobrutinib, Venetoclax, and Obinutuzumab As First-Line Treatment of Patients with Chronic Lymphocytic Leukemia (CLL) (ASH 2024) - P2 | "Introduction : Combined treatment with covalent BTK-inhibitor (cBTKi), such as ibrutinib, acalabrutinib, or zanubrutinib with BCL2-inhibitor, venetoclax, +/- CD20 monoclonal antibody obinutuzumab showed high rates of undetectable MRD (U-MRD4, 10-4 sensitivity) remission in patients (pts) with CLL (Jain, NEJM 2019; Munir NEJM 2023; Wierda, JCO 2021; Kater, NEJM Evidence 2022). Adverse event profile was similar to what was noted in previous studies with these agents. Updated data will be presented."

Clinical • IO biomarker • Chronic Lymphocytic Leukemia • Head and Neck Cancer • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Solid Tumor • Thrombocytopenia • TP53

Efficacy of pirtobrutinib monotherapy in treatment-naïve chronic lymphocytic leukemia: A Bayesian network meta-analysis of randomized controlled trials (ASH 2025) - P3 | "Background BRUIN CLL-314 (NCT05254743) is a global phase 3 open-label randomized controlled trial (RCT)comparing pirtobrutinib with ibrutinib (ibr) in both treatment-naïve (TN) and relapsed/refractory patients(pts) with CLL/SLL and no prior BTKi exposure...Thisresulted in two disconnected networks of NCCN-recommended therapies: Network1 includedpirtobrutinib, ibr, and zanubrutinib (zanu); Network2 included venetoclax (ven) + obinutuzumab (obi), ven+ ibr, acala (acala), acala + obi, acala + ven, and acala + obi + ven.In Network1, pirtobrutinib had an 87.5% probability of being ranked first for ORR (surface under thecumulative ranking curve [SUCRA]=96.8%), followed by zanu (5.7% probability of being first,SUCRA=64.2%)...While the efficacy of pirtobrutinib as measured by ORR andpreliminary PFS generate favorable point estimates relative to currently available therapy (i.e., ORs > 1and HRs < 1), caution is needed when interpreting the data due to the wide..."

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

A Multicenter Phase 2 Trial of Zanubrutinib, Obinutuzumab, and Venetoclax (BOVen) in Patients with Treatment-Naïve, TP53-Mutant Mantle Cell Lymphoma (ASH 2023) - P2 | "Obinutuzumab, ibrutinib, and venetoclax were well tolerated and efficacious in relapsed and untreated MCL patients (Le Gouill, Blood 2021). BOVen is a well-tolerated, outpatient regimen associated with high response rates and high rates of undetectable MRD in untreated TP53-mutant MCL. The early PFS and OS estimates with BOVen compare favorably with historical outcomes of chemoimmunotherapy in this high-risk subset of MCL. Based on this data, BOVen emerges as a promising treatment option for TP53-mutant MCL and, therefore, the study was expanded to include an additional 25 (total 50) TP53-mutant MCL patients."

Clinical • IO biomarker • P2 data • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Mantle Cell Lymphoma • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Thrombocytopenia • TP53

ZANUBRUTINIB PLUS OBINUTUZUMAB VERSUS OBINUTUZUMAB IN PATIENTS WITH RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA: UPDATED ANALYSIS OF THE ROSEWOOD STUDY (ICML 2023) - P2 | "A total of 114 (52.5%) pts were refractory to rituximab; 214 (98.6%) patients received prior immunochemotherapy. Prior exposure to anticancer drugs included anthracyclines (80.6%), cyclophosphamide (94.0%), and bendamustine (54.8%)... ZO demonstrated meaningful activity and a manageable safety profile in patients with heavily pretreated R/R FL, representing a potential novel therapy. Encore Abstract—previously submitted to ASCO 2023 and EHA 2023"

Clinical • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

Risk of Therapy-Related Myeloid Neoplasms in Patients With Chronic Lymphocytic Leukemia Treated With BTK Inhibitors: A Retrospective Multicenter Analysis Using the TriNetX Database (SOHO 2026) - "Adult patients with CLL treated with ibrutinib, acalabrutinib, or zanubrutinib were included. Patients with prior chemoimmunotherapy exposure, including fludarabine/cyclophosphamide, FCR, bendamustine/rituximab, and obinutuzumab/chlorambucil, were excluded to better isolate the long-term effects of BTKi therapy... In this large real-world TriNetX analysis of patients with CLL treated with BTK inhibitors and without prior chemoimmunotherapy exposure, therapy-related myeloid neoplasms were uncommon but increased over longer follow-up. MDS was the most frequent secondary myeloid neoplasm, followed by AML. The underlying immune dysregulation inherent to CLL, including impaired immune surveillance and defective T-cell function, may also contribute to the development of secondary malignancies in this population."

Retrospective data • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology

Acalabrutinib Monotherapy vs Investigator's Choice of Treatment in Patients With CL Leukaemia and Heart Failure (clinicaltrials.gov) - P4 | N=60 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Aug 2030 ➔ Sep 2032 | Trial primary completion date: Aug 2030 ➔ Sep 2032

Monotherapy • Trial completion date • Trial primary completion date • Cardiovascular • Chronic Lymphocytic Leukemia • Congestive Heart Failure • Heart Failure • Hematological Malignancies • Leukemia • Oncology

Micro-Dosed Obinutuzumab: A Novel Debulking Strategy in a Rare Case of Leukostasis From Chronic Lymphocytic Leukemia (SOHO 2026) - "The patient was later transitioned to zanubrutinib as a maintenance regimen. This case features the peculiar association of leukostasis and pseudohyperkalemia with CLL. Additionally, this case underlines the role of obinutuzumab microdosing as part of a tumor debulking regimen to alleviate the end-organ effects associated with leukostasis."

Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • CD5 • TP53

Consensus-Based Ranking of Determinants for Frontline Therapy Selection in Chronic Lymphocytic Leukemia: A Conjoint Analysis. (PubMed, Crit Rev Oncol Hematol) - "Furthermore, five commonly used regimens (ibrutinib, acalabrutinib, zanubrutinib, ibrutinib-venetoclax, venetoclax-obinutuzumab) were comparatively ranked according to their ability to accomplish each goal. Integrating conjoint analysis enables quantitative weighting of determinants and prioritization of treatment options beyond conventional categorical algorithms. The model supports evidence-based, individualized treatment strategies for CLL in clinical practice."

Journal • Review • Cardiovascular • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • TP53

Temporal Trends in Cardiovascular Toxicity With Second-Generation Bruton Tyrosine Kinase Inhibitors: Acalabrutinib vs Zanubrutinib (SOHO 2026) - "Background: The second-generation Bruton tyrosine kinase inhibitors (BTKi) acalabrutinib and zanubrutinib were designed to reduce the off-target cardiotoxicity of ibrutinib...Propensity score matching (1:1) balanced age, race, sex, CKD, diabetes, obesity, COPD, smoking, alcohol use, anticoagulant and antiplatelet use, concomitant CLL therapy (venetoclax, rituximab, obinutuzumab), and baseline hemoglobin and platelet counts... Zanubrutinib was associated with numerically higher rates of hypertension, whereas acalabrutinib showed significantly higher long-term risks of AF/flutter and major adverse cardiovascular events. These findings highlight the importance of individualized treatment selection, particularly in patients with underlying cardiac comorbidities. Prospective head-to-head studies are needed to validate these real-world observations."

Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Preliminary safety and efficacy of boven (Zanubrutinib, Obinutuzumab, and Venetoclax) as frontline therapy for older patients with Mantle Cell Lymphoma (ASH 2025) - "The MRD response-adapted BOVen triplet is highly active in older MCL patients with high rates of clinicaland molecular response. The 2-year PFS rate of 86% is encouraging; however, extended follow-up isnecessary to evaluate the 3-year PFS endpoint and the durability of response off treatment. Overall theregimen is safe and well-tolerated in older patients, with a toxicity profile similar to the prior experiencewith this triplet."

Clinical • CNS Disorders • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Mantle Cell Lymphoma • Nephrology • Neutropenia • Pneumonia • Respiratory Diseases • Thrombocytopenia • BIRC3 • CXCR4 • NOTCH2 • TP53

Study of Zanubrutinib, Obinutuzumab, and Venetoclax in Patients With Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Leukemia (SLL) (clinicaltrials.gov) - P2 | N=230 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Recruiting ➔ Active, not recruiting

Enrollment closed • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • TP53

Glofitamab Achieves Central Nervous System Disease Control in Relapsed B-ALL: A Case Report in a Transplant-Ineligible Jehovah's Witness Patient (SOHO 2026) - "Rituximab (8 cycles) was added to blinatumomab, and IT chemotherapy was intensified. Off-label zanubrutinib did not elicit a response...Off-label glofitamab with obinutuzumab pretreatment was initiated alongside additional radiation... To our knowledge, this is the first reported case of glofitamab achieving CNS disease control in B-ALL, extending prior observations from B-cell lymphomas in which glofitamab penetrates the CSF. The CD20-negative systemic relapse with maintained CNS control, in the setting of biopsy-confirmed CD20-positive CNS disease, supports compartment-specific selective pressure and biologic plausibility of CD20-directed bispecific activity in CNS sanctuary disease. Glofitamab may represent a therapeutic option for CNS-involved B-ALL in transplantineligible patients, including those declining blood products."

Case report • Clinical • IO biomarker • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19 • CD20

BTK Inhibitors Are Associated With Significantly Lower Hospitalization and Reduced Cardiovascular Morbidity Compared With Venetoclax-Based Regimens in CLL/SLL: A Propensity Score-Matched, Real-World Analysis (SOHO 2026) - " Using the TriNetX Research Network (111 health care organizations), we identified adults with CLL/SLL diagnosed between January 2016 and December 2023 who received BTKi monotherapy (ibrutinib, acalabrutinib, or zanubrutinib; n = 8661) or venetoclax-based regimens (venetoclax ± rituximab or obinutuzumab; n = 9823). In this large, propensity score-matched, real-world analysis, BTKi-based therapy was associated with significantly lower all-cause hospitalization, mortality, heart failure, and coronary artery disease compared with venetoclax-based regimens in patients with CLL/SLL. These findings highlight important real-world differences in health care utilization and cardiovascular outcomes that may inform treatment selection in this population."

Clinical • Real-world • Real-world evidence • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

Final analysis of the randomized phase 2 ROSEWOOD study of zanubrutinib + obinutuzumab vs obinutuzumab monotherapy in patients with relapsed/refractory follicular lymphoma (ASH 2025) - P2, P3 | "Introduction: While treatment advances have improved outcomes in follicular lymphoma (FL), manypatients experience multiple relapses with decreasing disease control intervals, highlighting the need fornew therapies. The final analysis of ROSEWOOD confirmed the favorable risk-benefit profile of ZO inpatients with R/R FL. The ORR and CR rate with ZO improved over time, responses remained durable, andthe PFS benefit over O was sustained. ZO had a manageable safety profile with no new safety signalsobserved."

Clinical • Monotherapy • P2 data • Atrial Fibrillation • Follicular Lymphoma • Hematological Malignancies • Hypertension • Infectious Disease • Lymphoma • Neutropenia • Pneumonia • Respiratory Diseases • Thrombocytopenia

When Is Stopping Safe? Fixed-Duration Therapy and Treatment-Free Remission in Hematologic Malignancies: A Scoping Review (SOHO 2026) - "Fixed-duration and MRD-guided discontinuation strategies can achieve durable TFR across CLL, MM, and MCL. Depth of MRD response, genomic risk, and re-treatment feasibility emerge as key determinants of safe treatment cessation. These findings support MRD as a clinically actionable biomarker for individualized and treatment-sparing therapeutic strategies."

Clinical • Review • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • IGH • TP53

Deep and Sustained Responses in Patients with CLL Treated with Zanubrutinib or Zanubrutinib + Obinutuzumab in Phase 1/2 AU-003 and Phase 1b GA-101 Studies: A Report from the Zanubrutinib Extension Study (ASH 2024) - P1, P1/2, P3 | "With a median follow-up of 6.5 years, the durability of these responses was demonstrated. The tolerability/safety profile of zanubrutinib, alone and in combination with obinutuzumab, remained favorable."

Clinical • P1/2 data • Atrial Fibrillation • Cardiovascular • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Malignancies • Hypertension • Infectious Disease • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • TP53

Recent advances and future perspectives in the treatment of chronic lymphocytic leukemia (PubMed, Rinsho Ketsueki) - "Current recommended first-line treatment options include covalent BTK inhibitor (cBTKi: ibrutinib, acalabrutinib±obinutuzumab, and zanubrutinib)-based regimens and BCL2 inhibitor (BCL2i: venetoclax)-containing regimens (venetoclax+obinutuzumab and venetoclax+ibrutinib). The non-covalent BTK inhibitor pirtobrutinib has recently been approved for patients with relapsed or refractory CLL who have previously been treated with a cBTKi. The durability of responses to initial and subsequent treatment of CLL has greatly extended life expectancy, and newer agents including BTK degraders, next-generation BCL2 inhibitors, novel antibodies (antibodies against BAFF, CD19, or ROR1, along with CD3×CD20 bispecific antibodies), and chimeric antigen receptor T-cell therapies should further improve quality of life for all patients."

Journal • Review • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • ROR1