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

Real-world efficacy of inaticabtagene autoleucel in adult B-cell acute lymphoblastic leukemia patients with high-risk molecular alterations (ASH 2025) - P | "The CR1-MRD⁻ group exhibited a trend toward superior median RFS compared to the combined CR1-MRD⁺ and R/R group (not reached vs. 404 days [95% CI: 30-777 days], P=0.073).In terms of post-CAR-T management, 20 patients received combination therapy (including three patients received tyrosine kinase inhibitors, one patients received zanubrutinib, two patients received pomalidomide, three patients received venetoclax, one patients received blinatumomab, one patients received inotuzumab ozogamicin, and four patients received allo-HSCT), while 21 patients underwent observation only. Front-line consolidation with CAR-T during CR1-MRD⁻ in patients with high-risk molecular alterations may yield better RFS outcomes compared to treatment administered in R/R or MRD⁺ settings. No RFS benefit from post-CAR-T combination therapy was observed in this cohort, highlighting the need for validation with longer follow-up durations and larger patient cohorts."

Clinical • IO biomarker • Real-world • Real-world effectiveness • Real-world evidence • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • IKZF1 • KMT2A • TP53

Safety and efficacy of ibrutinib as a first line agent for Mantle Cell Lymphoma : A systematic review and meta-analysis (ASH 2025) - "While standard first-line chemotherapy regimens include rituximab and bendamustine or cytarabine containing regimens, Bruton tyrosine kinase inhibitors (BTKis), such as ibrutinib and zanubrutinib, have demonstrated efficacy in relapsed or refractory MCL and are now being explored as frontline options. Notably, acalabrutinib in combination with bedamustine and rituximab has received FDA approval for treatment-naïve MCL patients who are ineligible for autologous hematopoietic stem cell transplantation (HSCT)...Conclusions Ibrutinib-based regimens demonstrate a high objective response rate and an acceptable safety profile when used as a first-line treatment for MCL. However, the substantial heterogeneity and potential publication bias is identified."

Retrospective data • Review • Atrial Fibrillation • Bone Marrow Transplantation • Cardiovascular • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma

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

Incidence of cardiac events associated with next-generation bruton tyrosine kinase (BTK) inhibitors compared to control in hematologic malignancies: A meta-analysis of randomized trials (ASH 2025) - "Most existing data are derived from studies of ibrutinib, the first generation BTKi which has known off-target receptor binding that may contribute to cardiotoxicity...Acalabrutinib was evaluated in four trials (ECHO, ELEVATE-TN, ASCEND, AMPLIFY), zanubrutinib in two (SEQUOIA, ROSEWOOD), and pirtobrutinib in one (BRUIN CLL-321)... This analysis of seven RCTs found that next-generation BTKi were associated with an elevated risk of atrial arrhythmias, particularly atrial fibrillation or flutter; however, the incidence of more severe cardiac events such as ventricular arrhythmias and myocardial infarction remains low and not significantly different between groups. The increased incidence of atrial rhythm disturbances may have important clinical implications, especially for patients with underlying cardiovascular risk. As use of these agents expands, clinicians should remain vigilant regarding potential cardiac effects and consider baseline evaluation and ongoing monitoring."

Retrospective data • Atrial Fibrillation • Chronic Lymphocytic Leukemia • Hematological Malignancies • Myocardial Infarction • Oncology • Ventricular Tachycardia

Real-world chronic lymphocytic leukemia/small lymphocytic lymphoma treatment patterns at Florida cancer specialists & research institute among patients receiving zanubrutinib immediately following prior BTKi therapy (ASH 2025) - P2 | "This retrospective, observational study examined the demographic and clinical characteristics, treatment patterns, reasons for treatment change, and treatment-limiting treatment-related adverse events (AEs) in patients with CLL/SLL who initiated zanubrutinib following an immediate switch from ibrutinib or acalabrutinib. Following the switch to zanubrutinib, recurrence of AEs was uncommon, and most patients stayed on treatment. These results support previously reported findings that zanubrutinib for CLL/SLL is well-tolerated despite prior BTKi therapy."

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

Real-world zanubrutinib treatment patterns in CLL/SLL among a curated sample of US community oncology patients with prior acalabrutinib therapy (ASH 2025) - "In head-to-head trials, zanubrutinib was superior to ibrutinib (ALPINE trial; hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.49-0.86), while acalabrutinib was noninferior to ibrutinib (ELEVATE-RR trial; HR: 1.00; 95% CI: 0.79-1.27) in patients with relapsed/refractory CLL. The primary reason for acalabrutinib discontinuation was toxicity. Consistent with previous research, real-world data from across the US have demonstrated that zanubrutinib was well tolerated and maintained effectiveness in patients with CLL who had received a prior BTK inhibitor."

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

Number of cardiac deaths associated with ibrutinib versus zanubrutinib for the treatment of chronic lymphocytic leukemia: A European risk-based estimation (ASH 2025) - P3 | "The study findings should be interpreted within the context of the model assumptions and data inputs. Further real-world studies using European registry data are needed to confirm these findings."

Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia

Number of patients needed to treat to prevent one atrial fibrillation event with zanubrutinib versus ibrutinib and acalabrutinib in B-cell malignancies (ASH 2025) - "This is an important consideration in clinical decision making where cardiovascular safety is a priority. Study findings should be interpretated within the context of the limitations including possible differential follow-up across studies, which may impact the incidence of AFib over time."

Clinical • Atrial Fibrillation • Cardiovascular • Hematological Malignancies • Oncology

Real-world treatment utilization, sequencing, and outcomes in Mantle Cell Lymphoma: Emerging treatment patterns in the United States (ASH 2025) - "Treatment regimens were categorized into 7 mutually exclusive groups: bendamustine (B)-based chemotherapy, R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, with or without cytarabine), Bruton tyrosine kinase inhibitors (BTKi; covalent: zanubrutinib, acalabrutinib, ibrutinib, and non-covalent: pirtobrutinib), bortezomib (bort)-based, venetoclax (ven)-based, intensive chemotherapy (high-dose cytarabine, HyperCVAD (hyperfractionated cyclophosphamide, vincristine, adriamycin, and dexamethasone, etc.), and other regimens (CAR-T or others). However, chemotherapy and/or immunotherapy were associated with the highest HCRU while BTKi were associated with the lowest HCRU. Notably, more than half of patients previously treated with BTKi and anti-CD20 therapies were subsequently treated with another covalent BTKi or a non-covalent BTKi, while approximately one-third received chemotherapy and/or immunotherapy, further emphasizing the need for novel..."

Clinical • HEOR • Real-world • Real-world evidence • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma

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

Zanubrutinib and pirtobrutinib (ZAP) but not ibrutinib and pirtobrutinib (IAP) show synergistic tumor cell killing and suppression of BTK and downstream signaling in MYD88 mutated lymphoma cells. (ASH 2025) - "The ZAP combination exhibited more potent synergistic inhibition of BTK signaling and downstream survival pathways versus zanubrutinib or pirtobrutinib alone or IAP in MYD88 mutated lymphomas. ZAP was also active in MYD88 mutated lymphoma cells expressing mutated BTK Cys481. The results support the investigation of ZAP as a novel therapeutic approach to overcome resistance and improve outcomes in patients with MYD88 mutated B-cell malignancies."

Tumor cell • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Lymphoplasmacytic Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia • GAPDH • MYD88 • PLCG2

Estimated cardiac deaths associated with treating chronic lymphocytic leukemia with ibrutinib versus zanubrutinib in the United States (ASH 2025) - P3 | "The study findings should be interpreted based on model assumptions and data inputs including potential differences in the patient populations treated in the clinical trials vs in the real world. Additional real-world studies are required to further validate the cardiac death risk of treating CLL patients with ibrutinib compared to zanubrutinib."

Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia

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

A matching-adjusted indirect comparison (MAIC) of zanubrutinib vs venetoclax + ibrutinib in treatment-naive chronic lymphocytic leukemia (CLL) (ASH 2025) - P2, P3 | "The phase 3 SEQUOIA trial (NCT03336333) evaluated zanubrutinib in treatment-naive (TN) patients without del(17p) mutations (arm A), in comparison with bendamustine + rituximab in the same population (arm B), and as monotherapy in patients with del(17p) mutations (arm C). With the longest available follow-up, zanubrutinib demonstrated a statistically significant PFS benefit over V+I in the GLOW population. In the comparison of CAPTIVATE vs SEQUOIA, a trend favoring zanubrutinib was observed, though statistical significance was not reached due to limited ESS caused by substantial baseline heterogeneity. These findings reinforce the robustness of the efficacy of zanubrutinib in TN patients with CLL and suggest improved outcomes compared with fixed-duration V+I across diverse patient populations."

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

Real-world comparison of BTKi monotherapy and fixed-duration BTKi–Venetoclax for first line treatment of chronic lymphocytic leukemia patients without TP53 mutations or IGHV rearrangement (ASH 2025) - "The population was further divided into two groups, those who received BTKi monotherapy (ibrutinib, zanubrutinib, acalabrutinib) and those who received fixed duration BTKi and venetoclax combination (IV). This real-world study suggests that BTKi monotherapy is non-inferior to fixed-duration BTKi and venetoclax combination therapy in terms of 2-year OS for treatment-naive B-CLL patients without TP53 mutations or IGHV gene rearrangement. We noted no statistically significant difference in the safety profiles of BTKi monotherapy and fixed-duration IV combination therapy."

Clinical • IO biomarker • Monotherapy • Real-world • Real-world evidence • Atherosclerosis • Atrial Fibrillation • Chronic Kidney Disease • Chronic Lymphocytic Leukemia • Chronic Obstructive Pulmonary Disease • CNS Disorders • Congestive Heart Failure • Diabetes • Dyslipidemia • Fibrosis • Genetic Disorders • Heart Failure • Hematological Disorders • Hematological Malignancies • Hepatology • Hypertension • Immunology • Infectious Disease • Leukemia • Liver Cirrhosis • Metabolic Disorders • Neutropenia • Obesity • Peripheral Arterial Disease • Pulmonary Disease • Renal Disease • Respiratory Diseases • Vascular Neurology • BCL2 • IGH • TP53

Real world outcomes of zanubrutinib monotherapy for CLL/SLL focusing on treatment discontinuation and BTKi switching: A single center retrospective analysis (ASH 2025) - "Our findings suggest that the real-world efficacy and safety profile of zanubrutinib for CLL/SLL is consistent with previous clinical trials. Real-world data support zanubrutinib continuous treatment as a preferred regimen for CLL/SLL patients. Discontinuation of zanubrutinb due to PD or AE is not common."

Monotherapy • Real-world • Real-world evidence • Retrospective data • Chronic Lymphocytic Leukemia • Dermatology • Hematological Malignancies • Hypertension • Infectious Disease • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Richter's Syndrome • Small Lymphocytic Lymphoma • IGH • TP53

Risk of second primary malignancies in patients with chronic lymphocytic leukemia treated with zanubrutinib and acalabrutinib: A real-world data analysis (ASH 2025) - "This study showed that zanubrutinib had a lower risk of some SPM, including basal cell carcinoma, diffuse large B-cell lymphoma, and lung cancer, than compared to acalabrutinib. For other malignancies, the incidence rate was relatively comparable between both groups, although both groups experienced higher SPM than incidence rate in the general population. However, the shorter follow-up for the zanubrutinib cohort and the retrospective nature of the analysis are the limitations of this study."

Clinical • Real-world • Real-world evidence • B Cell Lymphoma • Basal Cell Carcinoma • Bladder Cancer • Breast Cancer • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Genetic Disorders • Genito-urinary Cancer • Hematological Malignancies • Hodgkin Lymphoma • Kidney Cancer • Leukemia • Lung Cancer • Lymphoma • Non-Hodgkin’s Lymphoma • Non-melanoma Skin Cancer • Oncology • Prostate Cancer • Renal Cell Carcinoma • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma

Treatment with acalabrutinib in IGHV mutated setting and presence of splenomegaly are the main predictors of faster lymphocyte count decrease in CLL during monotherapy with cbtki (ASH 2025) - "Currently, all cBTKi available in clinical practice can be used in the first line of CLL therapy, based on the results of the phase III clinical trials RESONATE-2, ELEVATE-TN and SEQUOIA, which demonstrated the superiority of Ibrutinib, Acalabrutinib and Zanubrutinib, respectively, over chemotherapy/chemoimmunotherapy in terms of progression-free survival (PFS). In conclusion, differences in ALC modification over time seem to correlate to two factors: the presence of splenomegaly before starting treatment and having mutated IGHV status, the latter during therapy with Acalabrutinib. These evidences could have an important impact in the era of oral combination therapy, considering the role of BTKi as "demarginalizing agents" able to expose neoplastic lymphocytes to the pro-apoptotic action of BCL2 inhibitors in the peripheral blood."

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

A predictive model for treatment failure in CLL/SLL patients receiving BTK inhibitor: A multi-center retrospective study (ASH 2025) - " We conducted a retrospective analysis of CLL/SLL patients treated with ibrutinib or second-generation BTK inhibitors (orelabrutinib and zanubrutinib) across three centers in China. This multi-center study developed a validated predictive model for BTK inhibitor treatment failure in CLL/SLL, integrating genetic and metabolic factors. The model aids in early identification of high-risk patients, facilitating individualized treatment decisions and optimal resource allocation."

Predictive model • Retrospective data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Richter's Syndrome • Small Lymphocytic Lymphoma

Efficacy and safety of orelabrutinib monotherapy in patients with chronic lymphocytic leukemia: A retrospective real-world study (ASH 2025) - "Five pts had a history of BTKi treatment (ibrutinib, n=3; Zanubrutinib, n=2), all of whom switched due to inadequate efficacy or AEs. This real-world study suggested that orelabrutinib monotherapy showed promising efficacy and a favorable safety profile in pts with CLL, both as first-line and subsequent therapy. Further prospective investigations are needed to validate the observations."

IO biomarker • Monotherapy • Real-world • Real-world evidence • Retrospective data • Chronic Lymphocytic Leukemia • Diabetes • Dyslipidemia • Heart Failure • Hematological Malignancies • Hypertension • Leukemia • Metabolic Disorders • Thrombocytopenia • IGH • TP53

Efficacy and prognostic determinants of BTK inhibitors in chronic lymphocytic leukemia (CLL): A real-world single-center cohort study from China (ASH 2025) - "Bruton's tyrosine kinase (BTK) inhibitors, such as ibrutinib and zanubrutinib, have revolutionized CLL treatment by improving progression-free survival (PFS) and overall survival (OS). BTKi suspension negatively impacted OS, emphasizing the importance of treatment adherence. Further studies with larger cohorts and longer follow-up are warranted to refine risk stratification and optimize treatment approaches."

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

Adverse event profiles of acalabrutinib and zanubrutinib in chronic lymphocytic leukemia: A real-world comparison (ASH 2025) - "The study highlights a more favorable safety profile for zanubrutinib compared to acalabrutinib, with significant differences in fatal hemorrhage, infections, cytopenias, and cardiotoxicity. Safety alone is not enough to inform treatment decisions and it is critical to consider differences in efficacy, since a safer drug that is less effective is arguably not in the best interest of patients. A network meta-analysis provided further insight, suggesting that zanubrutinib was significantly associated with lower rates of disease progression or death when compared to acalabrutinib, with a favorable trend toward being better for overall survival despite this being non-statistically significant due to the confidence intervals."

Adverse events • Clinical • Real-world • Real-world evidence • Atrial Fibrillation • Candidiasis • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Hepatology • Infectious Disease • Leukemia • Liver Failure • Neutropenia • Pneumonia • Respiratory Diseases • Septic Shock • Thrombocytopenia

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

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