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

Genetic subtype-guided immunochemotherapy in relapsed and refractory diffuse large B cell lymphoma: a phase 2 investigator-initiated nonrandomized clinical trial (GUIDANCE-06). (PubMed, Signal Transduct Target Ther) - "The aim of this single-center, phase 2 trial was to evaluate the efficacy and safety of genetic subtype-guided immunochemotherapy (R-ICE-X) in patients with R/R DLBCL: R-ICE-zanubrutinib for MCD-like and BN2-like, R-ICE-lenalidomide for N1-like and NOS, R-ICE-decitabine for TP53Mut, R-ICE-chidamide for EZB-like, and R-ICE-tofacitinib for ST2-like subtype. Patients with mesenchymal or inflammatory lymphoma microenvironment subtypes benefited from R-ICE-X treatment. Our findings highlight the efficacy and safety of R-ICE-X, a mechanism-based tailored therapy, which dually targets genetic and microenvironmental alterations in R/R DLBCL."

Clinical • Journal • P2 data • B Cell Lymphoma • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia • Transplantation • CD70

DYNAMIC CHANGES OF ABSOLUTE CD4 COUNT IN PERIPHERAL BLOOD AS A PREDICTOR OF EFFICACY IN REFRACTORY/RELAPSED DLBCL HARBORING TP53 GENE MUTATIONSTREATED WITH GLOFITAMAB (ICML 2025) - "Despite these treatments (R-CHOP or Pola-R-CHP), relapse or refractory disease remains common...Given the nature of R/R DLBCL, chemo-free regimens included acalabrutinib (100 mg twice daily), zanubrutinib (160 mg twice daily), obutinib (150 mg once daily), sintilimab (200 mg per cycle), and glofitamab in combination with either polatuzumab vedotin (1.8 mg/kg) or lenalidomide (20 mg/day, days 1–14)... Chemo-free regimens incorporating glofitamab demonstrated high efficacy and good tolerability in R/R DLBCL patients with TP53 mutations. Additionally, dynamic changes in absolute CD4 count may serve as a preliminary predictor of glofitamab efficacy."

Clinical • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Lymphoma • Oncology • CD4 • TP53

Therapy Sequencing in Relapsed/Refractory MCL (ICML 2025) - P1, P1/2, P2, P3 | "Although a direct comparison between them has only been performed for ibrutinib and temsirolimus [23], covalent BTK inhibitor (cBTKi) single agent therapy has been consolidated as the standard of care after first-line CIT. Moreover, to address cBTKi failure, two anti-CD19 CAR-T cell therapy products, brexucabtagene autoleucel [20, 21] and lisocabtagene maraleucel [22], and the first noncovalent BTKi, pirtobrutinib [19], have recently been approved...Liso-cel only FDA approved; CIT, chemoimmunotherapy options include BR, R-BAC, R-CHOP, R-DHAP or R-DHAOx, R-GEMOx, paliative options (avoid bendamustine pre-CART apheresis); pirtobrutinib, available after cBTKi failure in second-line (EMA) but third-line (FDA); RM, rituximab maintenance...Orelabrutinib [18] is licensed only in China...Of note, both acalabrutinib and zanubrutinib induce lower rates of atrial fibrillation, hypertension, and bleeding compared to ibrutinib in randomized studies..."

IO biomarker • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Oncology • PLCG2 • TP53

Advances in the Management of Relapsed/Refractory CLL and Richter Transformation (ICML 2025) - P=N/A, P2, P3 | "BRUIN CLL-321 is a phase 3, registrational study that evaluated pirtobrutinib compared to the investigator's choice of idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR) [23]...Nemtabrutinib is now being evaluated in the registrational, phase 3 BELLWAVE-010 trial (NCT05947851) for patients with R/R CLL, comparing nemtabrutinib plus venetoclax to venetoclax plus rituximab...An ongoing, open-label, first-in-human phase 1/2 study is evaluating the BTK degrader BGB-16673 as monotherapy in patients with R/R CLL [27, 28]...NX-2127 is an investigational, first-in-class BTK degrader currently being evaluated in a phase 1 trial for patients with relapsed or refractory B-cell malignancies, CLL [29, 30]...NX-5948 is another investigational and more selective BTK degrader in an ongoing Phase 1a/1b clinical trial...This trial aims to establish lisaftoclax plus acalabrutinib as a potential alternative to venetoclax-based BTKi combination..."

IO biomarker • Acute Myelogenous Leukemia • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • Small Lymphocytic Lymphoma • BCL2L1 • TP53

Diagnosis and Management of Waldenstrom's Macroglobulinemia (ICML 2025) - P2 | "New or emerging options for patients progressing on c-BTKi include pirtobrutinib, BGB-16673, venetoclax, and sonrotoclax...CXCR4 antagonists such as plerixafor or ulocuplumab can sensitize CXCR4Mut-expressing WM cells to ibrutinib [22-24]...6 BTK Mutations BTKCys481 is the binding site for covalent BTK inhibitors (cBTK-i), including ibrutinib, zanubrutinib, acalabrutinib, orelabrutinib and tirabrutinib...For symptomatic treatment-naïve patients, chemoimmunotherapy with bendamustine and rituximab (Benda-R), dexamethasone, rituximab, and cyclophosphamide (DRC), as well as cBTK-i can be considered...Additional options in second or later relapse include re-use of chemotherapy if a response lasted for > 3 years, alternative chemoimmunotherapy, nucleoside analogs, or everolimus [38]...Zanubrutinib in combination with ixazomib and dexamethasone (ZID) is being investigated in a study in China (NCT04463953) and has shown high levels of response activity and good..."

IO biomarker • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia • BCLAF1 • CXCL12 • FOXO3 • IL10 • IL6 • IRAK4 • MYD88 • PLCG2 • SYK • TNFAIP3 • TRAF3IP2

Triplet Therapies in Chronic Lymphocytic Leukemia. (PubMed, Hematol Oncol Clin North Am) - "Triplet therapy regimens, which we define as the combination of a BTK inhibitor (ibrutinib, acalabrutinib, zanubrutinib, or pirtobrutinib), BCL2 inhibitor (venetoclax or sonrotoclax), and a CD20 antibody (obinutuzumab), have been developed in chronic lymphocytic leukemia (CLL). Herein, we comprehensively review the available clinical data for triplet regimens in treatment-naïve CLL, including an evidence-based discussion of the role of TP53 aberrancy in patients receiving triplet therapies, and of retreatment options after frontline triplet therapy. We also review ongoing trials with potential to further define the role of triplet therapies in treatment-naïve CLL."

Journal • Review • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • TP53

Considerations for the Practical Management of Cardiovascular Risk With Bruton's Tyrosine Kinase Inhibitors for Patients With CLL. (PubMed, Oncologist) - "Baseline and ongoing CV risk assessment, careful monitoring, management, and a multidisciplinary team approach are all critical to ensure optimal oncologic and CV outcomes for patients with CLL receiving BTKis."

Journal • Cardiovascular • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Hypertension • Leukemia • Oncology

Management of Relapsed and/or Refractory Chronic Lymphocytic Leukemia. (PubMed, Hematol Oncol Clin North Am) - "Covalent Bruton's tyrosine kinase inhibitors (cBTKis), including acalabrutinib and zanubrutinib, and the BCL2 inhibitor venetoclax are currently sequenced in both front-line and relapsed and/or refractory (R/R) chronic lymphocytic leukemia (CLL). We review treatment options for "double exposed" CLL including venetoclax retreatment, pirtobrutinib, and CAR T-cell therapy with lisocabtagene maraleucel. Emerging treatment options include agents in clinical trials such as BTK degraders and bispecific antibodies."

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

Simultaneous Presentation of Cutaneous Waldenström Macroglobulinemia and Acalabrutinib-Related Toxicity. (PubMed, Am J Dermatopathol) - "Next-generation Bruton tyrosine kinase inhibitors, such as zanubrutinib and acalabrutinib, have revolutionized WM treatment by enhancing selectivity but are associated with various dermatologic lesions. In addition, these patients are susceptible to opportunistic infections. Awareness of the various cutaneous reactions and vigilant monitoring are required."

Journal • Dermatitis • Dermatology • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Lymphoma • Lymphoplasmacytic Lymphoma • Monoclonal Gammopathy • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia

BGB-3111-111: Study of Zanubrutinib in Japanese Participants With B-Cell Malignancies (clinicaltrials.gov) - P1/2 | N=55 | Completed | Sponsor: BeiGene | Active, not recruiting ➔ Completed

Trial completion • Hematological Malignancies • Oncology

Differential modulation of Bruton's tyrosine kinase inhibitor selectivity on platelet GPVI and integrin αIIbβ3 bidirectional signalling via BTK/PLCγ2/PKCθ affects haemostasis and thrombosis. (PubMed, Br J Haematol) - "These findings demonstrate that the selectivity of ibrutinib and zanubrutinib leads to different inhibitory effects on platelets and integrin αIIbβ3 activation. Enhanced inhibition of the BTK/PLCγ2/PKCθ signalling pathway by ibrutinib can increase the bleeding risk related to BTKi."

Journal • Cardiovascular • Hematological Disorders • Thrombosis • PLCG2

Autoimmune complications of lymphoproliferative diseases (ICML 2025) - "Moreover, several drugs may be responsible for immune-mediated cytopenias, including several antibiotics (ceftriaxone, piperacillin, rifampin, nafcillin, erythromycin, ticarcillin, trimethoprim, sulfamethoxazole), and various other drugs (procainamide, quinine, phenacetin, diclofenac, cimetidine, hydrochlorothiazide, chlorpropamide) [8]...Ibrutinib, through the inhibition of autoantibodies producing B-cells and restoration of T-cell homeostasis seems safe, while some case reports of autoimmune diseases have been reported for idelalisib (autoimmune hepatitis, colitis) and venetoclax (AIHA) [5, 6]...They included nivolumab, followed by pembrolizumab, ipilimumab, and atezolizumab...In particular, in CLL several therapies have been reported effective in refractory cytopenias: alemtuzumab single agent, the combinations ibrutinib-rituximab, bendamustine-rituximab, and rituximab–cyclophosphamide-dexamethasone [34-37]. Notably, some of the new/experimental treatments for primary..."

IO biomarker • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Marginal Zone Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • Waldenstrom Macroglobulinemia • CTLA4 • HP • IL10 • PD-1 • TGFB1

A Confusing Case of Confusion: Bing-Neel Syndrome Treated With Zanubrutinib. (PubMed, EJHaem) - No abstract available

Journal

ORAL LENALIDOMIDE OR BTK INHIBITORS AS MAINTENANCE THERAPY SHOWED DURABLE EFFICACY AFTER THE FIRST REMISSION IN PCNSL PATIENTS (ICML 2025) - "The lenalidomide group received 25 mg qd on d1–21 of each cycle, and the BTKi group included patients on zanubrutinib (160 mg bid, n = 4), ibrutinib (420 mg qd, n = 3), or orelabrutinib (150 mg qd, n = 10)...The lenalidomide group primarily receiving 6 cycles R2-MTX (HD-MTX, lenalidomide, and rituximab (R); 79.49%), and the BTKi group primarily receiving POR-ROM (pomalidomide, orelabrutinib, and R for 4 cycles, followed by orelabrutinib, R, and HD-MTX for 2 cycles; 58.82%)...Maintenance therapy with lenalidomide or BTKi demonstrated PFS exceeding historical data from our institution and an acceptable safety profile. Further prospective studies with extended follow-up periods are warranted to confirm these findings and optimize maintenance therapy strategies for PCNSL."

Clinical • CNS Lymphoma • Lymphoma • Primary Central Nervous System Lymphoma

THE BTK DEGRADER BGB-16673 AND THE BCL2 INHIBITOR SONROTOCLAX SHOWS ANTI-TUMOR ACTIVITY AS SINGLE AGENTS AND IN COMBINATION IN MARGINAL ZONE LYMPHOMA MODELS (ICML 2025) - "The activity did not differ from the BTK inhibitor zanubrutinib and, accordingly, was limited in cells resistant to ibrutinib (n. = 2), idelalisib (n...= 1), and copanlisib/venetoclax (n...Karpas1718, SSK41, VL51 and HC1 were exposed to BGB-16673 plus lenalidomide, selinexor, venetoclax, sonrotoclax (BGB-11417), bendamustine, tazemetostat and rituximab... Its ability to degrade BTK protein, combined with its synergistic effects with other targeted therapies, positions BGB-16673 as a promising candidate for further development in MZL patients. The 2nd generation BCL2 inhibitor sonrotoclax appears as another drug to be explored in the same patient populations, possibly combining the two molecules."

B Cell Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Oncology • BCL2L1 • CRBN • MCL1

ZEBRA: Zanubrutinib, Bendamustine, Rituximab Prev. Untreated WM (clinicaltrials.gov) - P2 | N=55 | Recruiting | Sponsor: Massachusetts General Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Disorders • Hematological Malignancies • Lymphoma • Lymphoplasmacytic Lymphoma • Non-Hodgkin’s Lymphoma • Waldenstrom Macroglobulinemia

BGB-3111-218: Treatment of CD79B Mutant Relapsed/Refractory Diffuse Large B-Cell Lymphoma With Bruton Tyrosine Kinase Inhibitor Zanubrutinib (clinicaltrials.gov) - P2 | N=65 | Completed | Sponsor: BeiGene | Active, not recruiting ➔ Completed | Trial completion date: Oct 2025 ➔ Mar 2025 | Trial primary completion date: Oct 2025 ➔ Mar 2025

Trial completion • Trial completion date • Trial primary completion date • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD79B

ADVANCES IN DLBCL MANAGEMENT: HIGHLIGHTS FROM CHINA (ICML 2025) - "The DEB study is the first phase III trial to show that combining tucidinostat with R-CHOP regimen is a feasible and efficacious novel approach in previously untreated DLBCL patients with DE...Another study also shows promising prospects: polatuzumab vedotin, zanubrutinib, rituximab, and lenalidomide (Pola-ZR2) regimen in unfit or frail patients with DLBCL, the CR rate was 77% (17/22), and ORR was 86% (19/22). The Pola-ZR2 regimen demonstrates promising efficacy in unfit or frail patients with DLBCL. More clinical research results will be presented at this meeting."

IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Lymphoma • Oncology • BCL2 • MYC

The Bruton's tyrosine kinase inhibitor acalabrutinib aborts ongoing acute food-induced anaphylactic reactions in humanized mice. (PubMed, J Allergy Clin Immunol) - "Acalabrutinib can stop ongoing IgE-mediated anaphylaxis and prevent mortality in humanized mice. BTK inhibitors could be effective novel rescue medications given in conjunction with epinephrine for the treatment of anaphylaxis."

Journal • Preclinical • Allergy • Food Hypersensitivity • Immunology

A case report: capillary leak syndrome in a patient receiving high-dose methotrexate, Tislelizumab and zanubrutinib for CNS lymphoma. (PubMed, Cancer Chemother Pharmacol) - "CLS is a serious complication for DLBCL patients receiving high-dose MTX therapy."

Journal • Acute Kidney Injury • B Cell Lymphoma • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Nephrology • Non-Hodgkin’s Lymphoma • Oncology • Pain • Primary Central Nervous System Lymphoma • Renal Disease • Respiratory Diseases

POLATUZUMAB VEDOTIN WITH BTK INHIBITORS AND CHEMOTHERAPY SHOWS RAPID, DEEP RESPONSES IN NON-GCB DIFFUSE LARGE B-CELL LYMPHOMA (ICML 2025) - "Treatment-naïve patients received Pola-BTKi-RCHP: polatuzumab vedotin (1.8 mg/kg, Day 1), a BTK inhibitor (zanubrutinib 160 mg twice daily, acalabrutinib 100 mg twice daily, or orelabrutinib 150 mg once daily, Days 1–21), rituximab (375 mg/m2), cyclophosphamide (750 mg/m2), doxorubicin (50 mg/m2) on Day 1, and prednisone (100 mg daily, Days 1–5). Relapsed patients received Pola-BTKi-GemOx: polatuzumab vedotin (1.8 mg/kg, Day 1), a BTK inhibitor (same dosing), rituximab (375 mg/m2), gemcitabine (1000 mg/m2), and oxaliplatin (100 mg/m2) on Day 1... The Pola-BTKi-chemo regimen showed rapid efficacy and manageable safety in non-GCB DLBCL. Further studies on POLA and BTK inhibitor combinations are ongoing."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • BCL2 • MYC

EFFICACY AND SAFETY OF MINIMAL RESIDUAL DISEASE-GUIDED IMMUNOCHEMOTHERAPY PLUS FIXED-DURATION BTKi IN YOUNG, TREATMENT-NAÏVE CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS (ICML 2025) - "They received MRD-guided immunochemotherapy (bendamustine and rituximab, or fludarabine, cyclophosphamide, and rituximab) for 4 cycles, followed by 6 cycles of CD20 monoclonal antibody and continuous orelabrutinib or zanubrutinib. MRD-guided immunochemotherapy plus fixed-duration BTKi showed promising efficacy and safety in young, treatment-naïve CLL patients."

Clinical • Minimal residual disease • Residual disease • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • IGH • TP53

NOVEL ZCR (ZANUBRUTINIB, CHIDAMIDE, RITUXIMAB) ± CHOP REGIMEN DEMONSTRATES PROMISING EFFICACY IN FRONTLINE TREATMENT OF DOUBLE-EXPRESSOR DIFFUSE LARGE B-CELL LYMPHOMA (ICML 2025) - P2 | "This phase 2 trial demonstrates ZCR ± CHOP achieves superior CRR (83.3%) versus historical R-CHOP data, with manageable toxicity, and ctDNA emerges as a potential response-related biomarker. The findings provide evidence for chemotherapy reduction in DE-DLBCL through targeted induction strategies."

Clinical • Tumor mutational burden • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • TMB

SEQUOIA 5-year follow-up in arm C: Frontline zanubrutinib monotherapy in patients with del(17p) and treatment-naive chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). (BASCO-MN 2025) - No abstract available

Clinical • Monotherapy • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

Efficacy of zanubrutinib versus acalabrutinib for relapsed or refractory chronic lymphocytic leukemia (R/R CLL): a matching-adjusted indirect comparison (MAIC). (PubMed, Ther Adv Med Oncol) - "CR was significantly higher for zanubrutinib versus acalabrutinib (odds ratio = 2.90 (95% CI: 1.13-7.43); p = 0.0270). Zanubrutinib was associated with a significant PFS-INV and CR advantage over acalabrutinib, with a trend toward improvement in OS."

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