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

U.S. FDA Approves Tablet Formulation of BeOne’s BRUKINSA for All Approved Indications (Businesswire) - "BeOne Medicines...announced that the U.S. Food and Drug Administration (FDA) has approved a new tablet formulation of BRUKINSA (zanubrutinib) for all five approved indications....BRUKINSA tablets have the same efficacy and safety as BRUKINSA capsules based on the results of two single-dose, open-label, randomized Phase 1 crossover studies of healthy adults designed to establish bioequivalence....The recommended dose of BRUKINSA remains at 320 mg daily. The new BRUKINSA tablets are 160 mg each, allowing patients to take two tablets daily rather than four of the current 80 mg capsules....The BRUKINSA tablets will replace capsules starting in October 2025. The European Medicines Agency is currently reviewing a Type II variation marketing authorization application (MAA) for the new tablet formulation of BRUKINSA in all currently approved indications, with approval expected later this year."

EMA approval • FDA approval • Launch US • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Waldenstrom Macroglobulinemia

A Study of Mosunetuzumab in People With Follicular Lymphoma (clinicaltrials.gov) - P2 | N=76 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

CLL2-BZAG: Sequential Regimen of Bendamustine Followed by Obinutuzumab (GA101), Zanubrutinib (BGB-3111) and Venetoclax (ABT-199) in Patients With Relapsed/Refractory CLL (clinicaltrials.gov) - P2 | N=42 | Active, not recruiting | Sponsor: German CLL Study Group | Trial primary completion date: Feb 2025 ➔ Dec 2026

Trial primary completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2 • PLCG2

Glofitamab, Polatuzumab Vedotin and Zanubrutinib in First-line Elderly DLBCL (clinicaltrials.gov) - P2 | N=38 | Not yet recruiting | Sponsor: Shanghai Zhongshan Hospital

New P2 trial • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Rare Presentation of a B-cell Lymphoproliferative Disorder with Renal AL Amyloidosis: A Case Study (ERA 2025) - "Treatment commenced with the Bruton tyrosine kinase (BTK) inhibitor zanubrutinib at 160 mg twice daily... Light chain amyloidosis (AL) is a rare condition with growing prevalence. Typically associated with plasma cell dyscrasias producing monoclonal lambda light chains, AL amyloidosis can lead to severe organ damage. The occurrence of renal AL amyloidosis alongside chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) is exceptionally rare."

Case study • Clinical • Acute Kidney Injury • Amyloidosis • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Glomerulonephritis • Hematological Malignancies • Leukemia • Lymphoma • Monoclonal Gammopathy • Nephrology • Non-Hodgkin’s Lymphoma • Oncology • Renal Disease • Small Lymphocytic Lymphoma

Not just amyloidosis: the spectrum of Waldenstrom's macroglobulinemia-associated renal disease. (PubMed, Leuk Lymphoma) - "In this manuscript, we present a case of WM-associated heavy and light chain deposition disease successfully treated with the second-generation BTK inhibitor zanubrutinib, emphasizing the potential role of novel targeted agents in this setting. Additionally, we provide a brief review of renal complications associated with WM and discuss some therapeutic considerations. However, the available data are heterogeneous and insufficient to draw definitive conclusions regarding the relationship between clinical outcomes and specific treatment strategies."

Journal • Review • Amyloidosis • Hematological Disorders • Hematological Malignancies • Lymphoma • Lymphoplasmacytic Lymphoma • Nephrology • Renal Disease • Waldenstrom Macroglobulinemia

Glenmark Pharma to introduce DCGI-approved BRUKINSA in India to advance treatment of haematological malignancies (BioSpectrum India) - "Mumbai-based Glenmark Pharmaceuticals...has announced the upcoming launch of zanubrutinib in India following approval by the Drugs Controller General of India (DCGI). Zanubrutinib will be marketed in India under the brand name BRUKINSA, an innovative therapy developed by BeiGene (now BeOne Medicines), a global oncology leader committed to delivering advanced treatments for cancer patients worldwide. BRUKINSA is the first and only Bruton’s tyrosine kinase (BTK) inhibitor approved in India for the treatment of five distinct B-cell malignancies: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), and follicular lymphoma (FL)."

Approval • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Small Lymphocytic Lymphoma • Waldenstrom Macroglobulinemia

Feasibility of Bruton's Tyrosine Kinase Inhibitor Discontinuation in Chronic Lymphocytic Leukemia: The Patient Perspective. (PubMed, Clin Lymphoma Myeloma Leuk) - "These data provide a unique report of patient experiences. The data suggest that BTKi may be feasible and result in a period of treatment-free remission. The data also indicate that patients are generally relieved when they anticipate BTKi discontinuation and observe significant QOL improvements after BTKi discontinuation. As such, these data should prompt prospective study of time-limited BTKi therapy for CLL."

Journal • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Mood Disorders • Oncology • Psychiatry

Real-world comparative effectiveness of first-line Bruton tyrosine kinase inhibitors (BTKis) in patients with chronic lymphocytic leukemia (CLL). (ASCO 2025) - "In phase 3 randomized trials among pts with relapsed or refractory CLL, zanubrutinib (zanu) demonstrated superior efficacy vs ibrutinib (ibr), while acalabrutinib (acala) only showed noninferiority to ibr. Patients with zanu had significantly longer rwTTNT, rwTTD, and rwOS compared to those with ibr and longer trends compared to those with acala. Limitations include limited follow-up time for zanu vs ibr and acala."

Clinical • HEOR • Real-world • Real-world evidence • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • TP53

Real-world zanubrutinib treatment patterns in mantle cell lymphoma (MCL) among US community oncology patients with prior Bruton tyrosine kinase inhibitor (BTKi) therapy. (ASCO 2025) - "The FDA has approved acalabrutinib (acala), as a single agent and in combination with bendamustine and rituximab, and zanu for treating relapsed/refractory MCL. The first-generation BTKi, ibrutinib (ibr), was voluntarily withdrawn in April 2023... In the US community setting, most patients with MCL treated with zanu who had prior ibr or acala treatment discontinued ibr or acala within 1 year. Real-world data from across the US have demonstrated the effectiveness of zanu in MCL after treatment with another BTKi. Reasons for discontinuation are still to be examined."

Clinical • Real-world • Real-world evidence • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology

Real-world Bruton tyrosine kinase inhibitor (BTKi) use and clinical outcomes among patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). (ASCO 2025) - "The next-generation BTKi zanubrutinib (zanu) demonstrated superiority over the first-generation BTKi ibrutinib (ibr) in treating R/R CLL, while the second-generation BTKi acalabrutinib (acala) only showed noninferiority to ibr. In this real-world comparative effectiveness analysis in 1L CLL/SLL, patients who received zanu were significantly more likely to remain on treatment compared with those who received acala; they were also less likely to require the next LOT. Limitations include shorter follow-up time for zanu vs acala."

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

Real-world zanubrutinib treatment patterns in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) among US community oncology patients with prior acalabrutinib therapy. (ASCO 2025) - "Funded by BeiGene Background: Despite higher selectivity of the second-generation Bruton tyrosine kinase inhibitor (BTKi) acalabrutinib (acala) compared with the first-generation BTKi ibrutinib (ibr), a notable fraction of clinical trial patients treated with acala discontinued treatment due to adverse events. In the US community setting, most patients with CLL/SLL who received acala discontinued therapy within 1 year of initiation. After prior acala therapy, the majority of patients treated with zanu remained on treatment at data cut-off. Consistent with other real-world data from across the US, the effectiveness of zanu in CLL/SLL was demonstrated despite prior acala treatment."

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

Risk of hypertension in patients newly diagnosed with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and treated with covalent Bruton tyrosine kinase inhibitors (cBTKi): A real-world study. (ASCO 2025) - "This real-world study shows that patients newly diagnosed with CLL/SLL treated with 1L zanubrutinib or acalabrutinib had lower rates of developing new-onset HTN compared to patients treated with 1L ibrutinib."

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

Comparing real-world treatment patterns and outcomes of zanubrutinib and acalabrutinib in CLL/SLL at University of California academic health centers. (ASCO 2025) - "Funded by BeiGene Background: Newer BTK inhibitors zanubrutinib (ZANU) and acalabrutinib (ACA) are preferred over first-generation ibrutinib for chronic lymphocytic leukemia (CLL) treatment due to better toxicity profiles shown in randomized controlled trials. In this RW study, ZANU was associated with a lower discontinuation risk than ACA. Poorer survival outcomes were linked to older age, more comorbidities, lower socioeconomic status, and AA patients faced higher risks of treatment discontinuation. These findings emphasize the need for further investigation into underlying causes to guide clinical decisions and optimize CLL treatment strategies in diverse RW settings."

Clinical • HEOR • Real-world • Real-world evidence • Chronic Lymphocytic Leukemia • Small Lymphocytic Lymphoma

Adverse events of interest (AEIs) with zanubrutinib vs fixed-duration combination of venetoclax + obinutuzumab in treatment-naive (TN) chronic lymphocytic leukemia (CLL). (ASCO 2025) - P3 | "Hematologic toxicity rates were lower with zanu vs VenO in the analysis time window. Rates of TEAEs leading to discontinuation and infections excluding COVID-19 were lower with zanu with a median tx duration of 23.9 mo. Continuing zanu monotherapy does not appear to increase the risk of infection, even with much longer tx duration, compared with fixed-duration VenO."

Adverse events • Chronic Lymphocytic Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Novel Coronavirus Disease • Oncology • Thrombocytopenia

Efficacy of pemetrexed-based regimens in primary central nervous system lymphoma: A single-center experience. (ASCO 2025) - P2 | "Regimens included Pem in combination with rituximab (R) (n=4), R and temozolomide (n=3) or R and ibrutinib (n=2). Two patients were treated with Pem and zanubrutinib in the context of a clinical trial (NCT05681195)... The high response rates, along with outpatient administration and feasibility of combination with other PCNSL active agents, suggests that Pem-based regimens should be explored further in prospective studies. Additionally, Pem-based regimens can offer an effective bridge to ASCT, which is associated with prolonged survival, and should be also studied as a bridge to CAR T-cell therapy. Patient characteristics and outcomes in the HD-MTX refractory PCNSL cohort."

Clinical • B Cell Lymphoma • CNS Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma

Efficacy of continuous zanubrutinib vs fixed-duration venetoclax in combination with obinutuzumab in treatment-naive (TN) chronic lymphocytic leukemia (CLL): A matching-adjusted indirect comparison (MAIC). (ASCO 2025) - P3 | "This unanchored MAIC investigated the relative efficacy of zanu vs VenO and suggested zanu had longer PFS and a trend for extended OS. Results should be interpreted with considerations of MAIC model assumptions and limitations. Further studies are needed to confirm these findings."

Clinical • Combination therapy • Chronic Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Novel Coronavirus Disease • Oncology • B2M • IGH

Comparative efficacy of zanubrutinib (ZANU) versus fixed-duration acalabrutinib plus venetoclax (AV) for first-line treatment of chronic lymphocytic leukemia (CLL): A matching-adjusted indirect comparison (MAIC). (ASCO 2025) - P3 | "With the assumption of bendamustine plus rituximab (BR) and fludarabine plus cyclophosphamide and rituximab (FCR)/BR treated as common control arms, SEQUOIA and AMPLIFY can be linked through FCR/BR and the comparison of ZANU and AV were conducted in an anchored MAIC. This MAIC examined the relative efficacy of ZANU versus AV and suggested a significant PFS advantage for ZANU over AV regimen. Results should be interpreted with considerations of MAIC model assumptions. Future analyses upon trial data maturation are warranted."

Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • IGH • TP53

A network meta-analysis (NMA) of efficacy of zanubrutinib versus fixed-duration acalabrutinib plus venetoclax in treatment-naïve (TN) chronic lymphocytic leukemia (CLL). (ASCO 2025) - P3 | "Bendamustine plus rituximab (BR) and fludarabine plus cyclophosphamide and rituximab (FCR)/BR were assumed to be treated as common control arms in the network. This NMA found a statistically significant improvement in PFS for ZANU over AV for patients with low-risk TN CLL. The observed efficacy differences should be interpreted under the limitation and assumptions of NMA, with further analysis upon trial data maturation. *Estimates are calculated from digitalized KM curve."

Retrospective data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Novel Coronavirus Disease • Oncology • IGH • TP53

Real-world treatment utilization patterns, discontinuation and healthcare resource utilization of first-line (1L) bruton tyrosine kinase inhibitor (BTKi) therapy in chronic lymphocytic leukemia (CLL): Age-related disparity. (ASCO 2025) - " A retrospective observational study using the Symphony Integrated Dataverse was conducted to identify adult CLL patients initiating a 1L BTKi (zanubrutinib [ZANU], acalabrutinib [ACA] or ibrutinib [IBR]) treatment regimen from 02/2022 and 09/2024 (index period). This real-world study demonstrated that CLL patients treated with ZANU had longer TTD, lower discontinuation rates, and less HCRU than ACA and IBR across all patients and specifically in older patients ≥65 yrs. Further studies on long-term and clinical outcomes are warranted."

Clinical • HEOR • Real-world • Real-world evidence • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Serious infections in patients with CLL/SLL treated with combination venetoclax and obinutuzumab compared with those treated with zanubrutinib: A real-world study. (ASCO 2025) - "This real-world study showed that patients diagnosed with CLL/SLL treated with VO had a higher risk of serious infections than those treated with zanu. In patients with a higher risk of infections, zanu could be considered as a treatment option in lieu of VO. Serious infections during 12- and 18-month follow-up period."

Clinical • Real-world • Real-world evidence • Chronic Lymphocytic Leukemia • Infectious Disease • Small Lymphocytic Lymphoma

Comparative efficacy of ibrutinib versus other covalent Bruton tyrosine kinase inhibitors (cBTKis) in first-line (1L) chronic lymphocytic leukemia (CLL): A matched-adjusted indirect comparison (MAIC). (ASCO 2025) - P3 | "Funded by Pharmacyclics LLC, an AbbVie Company Background: Ibrutinib (ibr), acalabrutinib (acala), and zanubrutinib (zanu) are cBTKis approved for treatment of CLL, with demonstrated efficacy as a single-agent in 1L CLL treatment. This is the first MAIC analysis to compare long-term efficacy outcomes across cBTKis in the 1L treatment of CLL. In the absence of head-to-head 1L CLL trials, our results suggest that ibr provides similar efficacy outcomes to acala and zanu. Further analyses are needed to understand if cBTKis provide similar or different efficacy in specific pt populations, such as those with high-risk disease."

Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • B2M • TP53

Combination of zanubrutinib (zanu) + venetoclax (ven) for treatment-naive (TN) CLL/SLL: Results in SEQUOIA arm D. (ASCO 2025) - P3 | "Funded by BeiGene Clinical Trial Registration Number: NCT03336333 Background: Zanu monotherapy demonstrated superior progression-free survival (PFS) compared with bendamustine + rituximab in patients (pts) without del(17p) at 26.2-month follow-up and sustained PFS benefit at 5-year follow-up. SEQUOIA arm D data demonstrate promising efficacy and tolerability of zanu + ven combination treatment in TN CLL/SLL, regardless of del(17p) and/or TP53 mutation status. The safety profile of zanu + ven was consistent with results of prior zanu studies, and no new safety signals were identified."

B Cell Lymphoma • Cardiovascular • Chronic Lymphocytic Leukemia • Hematological Disorders • Hypertension • Infectious Disease • Neutropenia • Small Lymphocytic Lymphoma • BCL2 • IGH

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). (ASCO 2025) - P3 | "Initial results from the SEQUOIA study (NCT03336333), at a median follow-up of 26.2 mo, demonstrated superior progression-free survival (PFS) by independent review with zanu vs bendamustine + rituximab (arms A and B) in patients (pts) with treatment-naive (TN) CLL/SLL without del(17p) as well as high overall response rate (ORR) and PFS benefit in pts with del(17p) (arm C). With this 5-y follow-up in SEQUOIA, the efficacy of zanu in TN higher-risk pts with del(17p) was maintained, and pts continue to demonstrate PFS benefits consistent with the randomized cohort of pts without del(17p) (arm A). Additionally, with longer-term follow-up, no new safety signals were identified. This update, in the largest cohort of uniformly treated pts with del(17p), suggests that zanu remains a valuable frontline treatment option for patients with or without del(17p) CLL/SLL."

Clinical • Monotherapy • Anemia • Atrial Fibrillation • Cardiovascular • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Hypertension • Infectious Disease • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • Small Lymphocytic Lymphoma • Thrombocytopenia • TP53

CHEMO-FREE REGIMENS CONTAINING GLOFITAMAB ARE SIGNIFICANTLY BENEFICIAL FOR RELAPSED/REFRACTORY DIFFUSE LARGE B CELL LYMPHOMA PATIENTS WITH TP53 GENE MUTATIONS: REAL-WORLD DATA FROM MULTI-CENTERS IN CHINA (EHA 2025) - "Background: TP53 gene mutations are an independent risk factor for the overall survival of patients with diffuse large B cell lymphoma (DLBCL), even though they receive the R-CHOP or Pola-R-CHP regimen as the frontline chemotherapy...Based on the nature of R/R DLBCL, chemo-free regimens are as follows below, acalabrutinib (100 mg twice daily) or zanubrutinib (160 mg twice daily) and obutinib (150 mg once daily), sintilimab (200 mg per cycle); glofitamab combined with polatuzumab vedotin (1.8 mg/kg) or lenalidomide (20 mg/day, days 1-14)... The chemo-free regimens combined with glofitamab displayed high efficacy and good tolerability in R/R DLBCL patients with TP53 gene mutations."

Clinical • Real-world • Real-world evidence • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • TP53