Imbruvica (ibrutinib) / AbbVie, J&J, Royalty - LARVOL DELTA

Ibrutinib and Palbociclib in Treating Patients With Previously Treated Mantle Cell Lymphoma (clinicaltrials.gov) - P1 | N=28 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jun 2026 ➔ Dec 2026

Trial completion date • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • CCND1 • CD5

Phase IB/II trial of epcoritamab plus ibrutinib in patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma (ASH 2025) - P1/2 | "Further, we will examine tumor samples obtained before starting treatment and at relapse/progression to explore aspects of the microenvironment that may contribute to treatment failure. Study status: The study is currently enrolling patients."

Clinical • P1/2 data • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Large B Cell Lymphoma • Leukemia • Lymphoma • Mediastinal B Cell Lymphoma • Non-Hodgkin’s Lymphoma • Primary Mediastinal Large B-Cell Lymphoma • BCL2 • BCL6

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

Real-world chronic lymphocytic leukemia (CLL)–specific biomarker testing patterns and frontline treatment patterns in patients with CLL/small lymphocytic lymphoma (SLL) (ASH 2025) - "For patients (pts) with higher-risk genomic aberrations (eg, del[17p], TP53 gene mutation, unmutated immunoglobulin heavy chain variable region [IGHV]) targeted agents such as second-generation Bruton tyrosine kinase (BTK) inhibitors are preferred over chemoimmunotherapy (CIT) or ibrutinib as frontline (1L) tx options (NCCN, 2024; CLL Society, 2024)... In this real-world study among pts treated in an integrated delivery system in Texas, frequencies of test orders for CLL-specific biomarkers, especially DNA sequencing for TP53 and IGHV, remained low in recent years. Pts with testing were more likely to receive second-generation BTK inhibitor- or BCL2 inhibitor-based tx, while pts without testing were more likely to receive CIT. The observed differences in testing rates by tx groups and factors associated with social and practice patterns highlight opportunities to improve quality of care and optimize tx decisions."

Biomarker • Clinical • IO biomarker • Real-world • Real-world evidence • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Leukemia • Lymphoma • Richter's Syndrome • Small Lymphocytic Lymphoma • 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

Incidence of cardiac-related deaths among patients aged ≥65 years with B-cell malignancies treated with ibrutinib (ASH 2025) - "These results were consistent with previous smaller studies with ibr (Lampson Blood 2017; Guha J Am Coll Cardiol 2020). Additional assessment of secondary causes of death and diagnosis near death are needed to verify study results, as well as extending to other Bruton tyrosine kinase inhibitors."

Clinical • Atrial Fibrillation • Chronic Lymphocytic Leukemia • Congestive Heart Failure • Follicular Lymphoma • Heart Failure • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Myocardial Infarction • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • Ventricular Tachycardia • Waldenstrom Macroglobulinemia

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

Improved survival in chronic lymphocytic leukemia over two decades: A SEER-based population analysis (2000–2021) (ASH 2025) - "Over the past twenty years, there has been a marked evolution in the landscape of treatment modalities, typified by the incorporation of chemoimmunotherapy in the early 2000s, followed by the advent of targeted therapeutic agents, including Bruton tyrosine kinase (BTK) inhibitors (ibrutinib, acalabrutinib) and BCL2 inhibitors (venetoclax) commencing in the year 2013. Among individuals diagnosed with Chronic Lymphocytic Leukemia (CLL) from the year 2000 to 2021, relative survival rates exhibited significant enhancement across all assessed temporal intervals: 1-year: 85.9% 2-year: 81.2% 5-year: 75.4% - Sex disparities: Female patients demonstrated a superior 5-year survival rate (77.3%) in comparison to their male counterparts (73.5%). - Age disparities: Patients below the age of 65 exhibited a 5-year survival rate exceeding 80%, Whereas patients aged 65 years and older experienced survival rates below 70% prior to the year 2010, yet this figure improved to over 74%..."

Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia

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

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

Feasibility assessment of indirect treatment comparison between off-label rituximab and novel treatments in patients with warm autoimmune hemolytic anemia (ASH 2025) - "Among the clinical trials included, five studied rituximab, in combination with prednisone, prednisolone, ibrutinib, or bortezomib. Three trials studied fostamatinib, while other studied treatments included pegcetacoplan, sovleplenib, parsaclisib, and rilzabrutinib...Future work should consider de novo sources of real-world evidence for rituximab that more closely align with registrational trial characteristics and endpoint definitions. However, aligning timing of endpoint measurements between registration trials and real-world data to match definitions remains challenging."

Clinical • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology

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

Quality initiative in first-line chronic lymphocytic leukemia /small lymphocytic lymphoma assessing the use of 2nd generation BTKi therapy and impact on cardiac medical conditions patients experience on treatment (ASH 2025) - "Those practices that participated in the CLL/SLL QI had increased guideline concordance per the NCCN of using 2nd generation BTKi drugs and had lower rates of CV-ME due to the lower use of ibrutinib in the treatment of CLL/SLL patients in the first-line."

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

Large language models extract diverse manifestations of chronic GVHD from unstructured clinical documentation (ASH 2025) - "Of these patients, 58 were steroid refractory/dependent and received a second line immunosuppressant such as ruxolitinib (76% of patients), belumosudil (14%), or ibrutinib (16%). Presence of any non-scorable symptom (i.e. muscle symptom, nasal/sinus symptoms, serositis, or capillary leak syndrome) in the two weeks leading up to the start of corticosteroid therapy occurred more frequently in patients who required additional immunosuppression (11/58, 19.0%) compared those who received prednisone alone (6/85, 7.1%) with an odds ratio of 0.32 (pvalue 0.04)...This approach enabled the construction of a comprehensive database of events post-transplant. We anticipate that this database will facilitate future investigation into distinct patterns of cGVHD activity, creating well-calibrated metrics of disease severity, and predicting response to immunosuppressive therapy."

Clinical • Cardiovascular • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Immunology • Otorhinolaryngology

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

Integrating oncofertility: Contraceptive guidance in chronic lymphocytic leukemia (ASH 2025) - "BTK inhibitors (e.g ibrutinib) increase thrombotic risk through platelet dysfunction and coagulopathy and may reduce the efficacy of estrogen-containing contraceptives through CYP3A4 induction. Similarly, BCL-2 inhibitors (e.g venetoclax) increase thrombotic risk, particularly when combined with other platelet-function impairing agents, warranting cautious use of estrogen-based contraceptives...Furthermore, conventional chemotherapy (e.g fludarabine, cyclophosphamide) and some target therapies (e.g idelalisib) also present high thrombosis risk and hepatotoxicity, potentially impairing hormonal contraceptive metabolism...On the other hand, immunotherapy agents (e.g rituximab) demonstrate variable thrombosis risks, especially when used in combination therapies... Contraception in women with chronic lymphocytic leukemia (CLL) presents complex challenges requiring individualized care. As many CLL treatments have gonadotoxic and teratogenic properties, it is imperative to..."

Chronic Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Long-acting Reversible Contraceptives • Thrombosis • CYP3A4

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

Evaluation of response assessment in chronic lymphocytic leukaemia using measurable residual disease by flow cytometry: Prospective observational study. (ASH 2025) - "Treatments included Acalabrutinib (37.9 %), Bendamustine plus Rituximab (34.5%), Ibrutinib plus Rituximab (17.2%), and single cases of Venetoclax plus Rituximab, R-CHOP, and Mini R-CHOP plus Acalabrutinib. The study is limited by a small sample size for statistical analysis and a shorter follow-up period. Overcoming these limitations would give an answer for the accurate estimation of response to therapy in CLL for future response-guided therapy."

Clinical • IO biomarker • Observational data • Residual disease • Aplastic Anemia • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Infectious Disease • Leukemia • Lymphoma • Neutropenia • Richter's Syndrome • Thrombocytopenia • IGH • NOTCH1 • TP53

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

Consensus on optimal use of fixed-duration BTK inhibitor and venetoclax therapy in CLL: A delphi study comparing human expertise and AI methodologies (ASH 2025) - "- Venetoclax plus first-generation BTKi (ibrutinib) FD combinations may not be recommended for elderly patients over 70 years who are unfit, regardless of the specific comorbidity. This consensus underscores the critical importance of adopting a personalized approach to optimize the selection of BTKis within venetoclax-based FD therapies. Specifically, for elderly patients—regardless of the presence of cardiovascular comorbidities—second-generation BTKis, such as acalabrutinib, should be prioritized in venetoclax-based FD regimens. Our study is pioneering in its comparative analysis of Delphi-derived expert consensus and responses generated by ChatGPT-4."

IO biomarker • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Leukemia • Lymphoma • Nephrology • IGH • TP53