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

Role of Autologous Stem Cell Transplantation in the Context of Ibrutinib-Containing First-Line Treatment in Younger Patients with Mantle Cell Lymphoma: Results from the Randomized Triangle Trial By the European MCL Network (ASH 2024) - "In the context of ibrutinib- and high-dose cytarabine-containing induction immuno-chemotherapy and ibrutinib maintenance, the addition of ASCT failed to show FFS superiority, while increasing toxicity during maintenance/follow-up. According to the pre-defined decision strategy, ibrutinib+R-CHOP/R-DHAP induction followed by 2 years of ibrutinib maintenance should be the new standard of care in younger MCL patients, thus ending the era of ASCT for MCL patients."

Clinical • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • Transplantation

First-line ibrutinib plus venetoclax for non-blastoid mantle cell lymphoma in patients ≥65 years or with TP53 mutations. (PubMed, Blood) - P3 | "First-line ibrutinib plus venetoclax showed promising efficacy, with high CR rates and durable remissions, in patients with previously untreated non-blastoid MCL and may be an option for patients ≥65 years or patients of any age with TP53m. NCT03112174."

Journal • Fatigue • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Mantle Cell Lymphoma • Neutropenia • Novel Coronavirus Disease • Oncology • TP53

Contemporary Treatment and Survival Outcomes in Mantle Cell Lymphoma: A National Real-World Analysis From REALYSA, a LYSA Cohort. (PubMed, Hematol Oncol) - P=N/A | "Older patients were treated with bendamustine-rituximab (28%), R-CHOP (18%), and low-dose cytarabine (20%)...In the second-line setting (n = 72), most patients were POD24 (89%) and 56% received ibrutinib, yet outcomes remained poor (CR 24%, ORR 35%, median EFS and OS of 6.3 and 25.6 months, respectively). These findings underscore the need for improved strategies for older and high-risk patients. Retrospective landmark analyses suggest a potential association between RM and improved EFS but are limited by baseline differences between groups."

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

Ibrutinib plus rituximab versus ibrutinib monotherapy in patients with Waldenström macroglobulinemia: A pooled analysis. (PubMed, Blood Adv) - P2, P3 | "I+R significantly improved PFS over I in patients with CXCR4-mutated WM, along with a non-significant increase in VGPR in this subgroup. These results support routine CXCR4 testing in patients with WM and clinical trials of rituximab with covalent or non-covalent BTK inhibitors."

Journal • Monotherapy • Retrospective data • Hematological Disorders • Lymphoma • Lymphoplasmacytic Lymphoma • Waldenstrom Macroglobulinemia • CXCR4 • MYD88

Fixed-duration versus continuous targeted treatment for previously untreated chronic lymphocytic leukemia: Results from the randomized CLL17 trial (ASH 2025) - P3 | "Here we present data of a prospective trial comparing continuous ibrutinib (I)monotherapy to fixed-duration venetoclax plus obinutuzumab (VO) and venetoclax plus ibrutinib (VI) forCLL. Covid-19 infection was reported in 38.3%, 42.2% and 39.3% of pts; cardiac disordersoccurred in 13.9%, 23.8% and 34.6% of pts; second cancers were reported in 11.5%, 11.2% and 18.5% ofpts, respectively.ConclusionThis is the first phase 3 trial comparing the main paradigms of continuous vs fixed-duration targetedtherapy of CLL. Early findings indicate that fixed-duration treatment with VO or VI are non-inferior tocontinuous treatment with I and may therefore represent the preferred treatment option for pts withpreviously untreated CLL."

Clinical • Chronic Lymphocytic Leukemia • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Infectious Disease • Leukemia • IGH • TP53

Ibrutinib with venetoclax in patients with relapsed/refractory chronic lymphocytic leukemia: A phase II study. (PubMed, Blood Cancer Discov) - "Grade ≥3 neutropenia and thrombocytopenia occurred in 38% and 13% of patients, respectively. The 24-cycle ibrutinib + venetoclax combination led to high rates of CR/CRi and bone marrow U-MRD4 in patients with R/R CLL."

Journal • P2 data • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Thrombocytopenia • IGH • TP53

Fixed-duration obinutuzumab-ibrutinib-venetoclax for Richter's transformation: results from the phase II GIVeRS trial. (PubMed, Haematologica) - "Not available."

Journal • P2 data • Richter's Syndrome

Aberrant expression of MERTK activates BCR via CD79a in CLL cells: alternative therapeutic strategy for relapsed/refractory CLL. (PubMed, Leukemia) - "More significantly, ibrutinib-resistant CLL cells expressed high-levels of MERTK and that, UNC-2025 synergistically induced apoptosis when combined with venetoclax. Thus, high MERTK-levels in CLL cells may be associated with ibrutinib-resistance underscoring the potential use of UNC-2025/venetoclax combination in treating relapsed/refractory patients."

Journal • Chronic Lymphocytic Leukemia • AXL • CD79A • GAS6 • LYN • MERTK

Bilateral Conjunctival Small Lymphocytic Lymphoma Simulating Inflammatory Ocular Surface Disease: A Case Report. (PubMed, Vision (Basel)) - "Systemic staging with 18F-FDG PET/CT and bone marrow biopsy revealed no definite extra-conjunctival disease. After multidisciplinary review of observation, local radiotherapy and surgical excision, systemic therapy was preferred given the bilateral, recurrent and symptomatic course, and oral ibrutinib 420 mg once daily achieved complete clinical regression at three months and a sustained ocular response at two years, with indefinite haematological and ophthalmological surveillance planned."

Journal • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Ocular Inflammation • Oncology • Ophthalmology • Pain • Sarcoidosis • Scleritis • Small Lymphocytic Lymphoma • CCND1 • CD20 • CD5 • FCER2 • MME

BRUIN-MCL-321: Study of BTK Inhibitor LOXO-305 Versus Approved BTK Inhibitor Drugs in Patients With Mantle Cell Lymphoma (MCL) (clinicaltrials.gov) - P3 | N=500 | Active, not recruiting | Sponsor: Loxo Oncology, Inc. | Trial completion date: Apr 2028 ➔ Jun 2030 | Trial primary completion date: Jan 2027 ➔ Nov 2027

Trial completion date • Trial primary completion date • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology

A PHASE 1 STUDY OF PARSACLISIB IN COMBINATION WITH RITUXIMAB, BENDAMUSTINE + RITUXIMAB, OR IBRUTINIB IN PATIENTS WITH PREVIOUSLY TREATED B-CELL LYMPHOMA (CITADEL-112): PRELIMINARY SAFETY RESULTS (EHA 2022) - P1 | "Parsaclisib dose interruption or dose reduction due to TEAEs occurred in 75.0% and 18.8% of pts, respectively, in Tmt A; 66.7% and 27.8% of pts, respectively, in Tmt B; and 56.3% and 18.8% of pts, respectively, in Tmt C. Conclusion Parsaclisib 20 mg QD for 8 weeks followed by 20 mg QW can be safely combined with RIT, RIT + BEN, or IBR in pts with R/R B-cell lymphomas. The tolerability profile of the combination regimens was manageable, with no unexpected safety concerns."

Clinical • Combination therapy • P1 data • Acute Kidney Injury • Anemia • Atrial Fibrillation • Bone Marrow Transplantation • Cardiovascular • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Interstitial Lung Disease • Lymphoma • Marginal Zone Lymphoma • Nephrology • Neutropenia • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • Pain • Pneumonia • Pulmonary Disease • Renal Disease • Respiratory Diseases • Transplantation • PIK3CD

Circulating Tumor Cells and Plasma MYD88 Mutation Allele Fraction as Prognostic Markers for Staging and Ibrutinib Response in Waldenström Macroglobulinemia (IMS 2026) - "Our findings support the potential of liquid biopsy with CTCs and MYD88 L265P MAF as a potential tool for assessing dynamic changes in disease status and treatment efficacy."

Biomarker • Circulating tumor cells • IO biomarker • Tumor cell • Hematological Disorders • Lymphoma • Lymphoplasmacytic Lymphoma • Monoclonal Gammopathy • Oncology • Waldenstrom Macroglobulinemia • CD19 • CD20 • CD22 • CD27 • CD5 • CTCs • FCER2 • IL2RA • MYD88

Proteogenomic Integration Reveals Predictive Signatures of Ibrutinib Response in Waldenström Macroglobulinemia (IMS 2026) - "In conclusion, our results highlight the identification of plasma biomarkers for WM and demonstrate shared programs between the two compartments that can be used to elucidate response status and predict progression."

IO biomarker • Lymphoma • Lymphoplasmacytic Lymphoma • Waldenstrom Macroglobulinemia • AKT2 • CD9 • CTLA4 • CXCL13 • CXCL5 • EIF4E • IRAK4 • LAG3 • PCDH9 • RICTOR • TIGIT • XBP1

Distinct Immune and Genomic Signatures Predict Resistance to Ibrutinib Therapy in Waldenström Macroglobulinemia (IMS 2026) - "Finally, we showed that integrating tumor with immune cell compartments can significantly improve ibrutinib response prediction scoring highlighting potential mechanisms of resistance that could serve for the identification of predictive biomarkers for BTK-based therapy in WM."

Hematological Disorders • Lymphoma • Lymphoplasmacytic Lymphoma • Waldenstrom Macroglobulinemia • BCL7A • CD4 • CD8 • DUSP2 • GZMB • IRAK1 • IRF4 • NFKBIA • NR4A1 • SELL • TNFA

Circulating Tumor Cells and Plasma MYD88 Mutation Allele Fraction as Prognostic Markers for Staging and Ibrutinib Response in Waldenström Macroglobulinemia (IMS 2026) - "Our findings support the potential of liquid biopsy with CTCs and MYD88 L265P MAF as a potential tool for assessing dynamic changes in disease status and treatment efficacy."

Biomarker • Circulating tumor cells • IO biomarker • Tumor cell • Hematological Disorders • Lymphoma • Lymphoplasmacytic Lymphoma • Monoclonal Gammopathy • Oncology • Waldenstrom Macroglobulinemia • CD19 • CD20 • CD22 • CD27 • CD5 • CTCs • FCER2 • IL2RA • MYD88

Proteogenomic Integration Reveals Predictive Signatures of Ibrutinib Response in Waldenström Macroglobulinemia (IMS 2026) - "In conclusion, our results highlight the identification of plasma biomarkers for WM and demonstrate shared programs between the two compartments that can be used to elucidate response status and predict progression."

IO biomarker • Lymphoma • Lymphoplasmacytic Lymphoma • Waldenstrom Macroglobulinemia • AKT2 • CD9 • CTLA4 • CXCL13 • CXCL5 • EIF4E • IRAK4 • LAG3 • PCDH9 • RICTOR • TIGIT • XBP1

Combination Targeted Therapy in Relapsed Diffuse Large B-Cell Lymphoma. (PubMed, N Engl J Med) - P1/2 | "Treatment with ViPOR was associated with durable remissions in patients with specific molecular DLBCL subtypes and was associated with mainly reversible adverse events. (Funded by the Intramural Research Program of the National Cancer Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health and others; ClinicalTrials.gov number, NCT03223610.)."

IO biomarker • Journal • P1 data • P2 data • Cerebral Hemorrhage • CNS Disorders • Diffuse Large B Cell Lymphoma • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia • BCL2 • BCL6 • MYC

Comparing Ibrutinib With Acalabrutinib and Zanubrutinib in B-Cell Malignancies: A Real-World Study of Mortality and Toxicity (SOHO 2026) - "In this large, propensity-matched real-world cohort of patients with B-cell malignancies, ibrutinib was associated with higher mortality and greater cardiopulmonary toxicity than acalabrutinib and zanubrutinib. The excess mortality with ibrutinib may reflect off-target kinase inhibition and the resulting burden of atrial fibrillation, heart failure, and respiratory complications in an older, comorbid population. These findings support preferential use of second-generation BTK inhibitors when feasible and underscore the need for careful cardiovascular risk assessment in patients receiving ibrutinib."

Clinical • Real-world • Real-world evidence • Chronic Lymphocytic Leukemia • Hematological Malignancies • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Oncology • Waldenstrom Macroglobulinemia

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

RITUXIMAB AND IBRUTINIB COMBINATION IS SAFE AND EFFECTIVE IN UNTREATED EXTRANODAL MARGINAL ZONE LYMPHOMAS: FIRST ANALYSIS OF THE IELSG47/MALIBU PHASE II STUDY (ICML 2025) - "The combination of rituximab and ibrutinib shows significant activity in EMZL, with a manageable toxicity profile. Careful patient selection and monitoring are required to minimize the risk of adverse cardiovascular events."

P2 data • Extranodal Marginal Zone Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Oncology

Acalabrutinib in Combination with Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy in Relapsed/Refractory B-Cell Lymphoma: A Phase I/II Study of Safety, Efficacy and Immune Correlative Analysis (ASH 2023) - P1/2 | "BTK inhibitors, ibrutinib and acalabrutinib are immunomodulatory and may enhance CAR-T expansion, engraftment and tumor clearance while decreasing the frequency and severity of CRS in chronic lymphocytic leukemia (Qin, et al...Three (20%) patients had grade 3 ICANS which resolved with dexamethasone and anakinra or tocilizumab...Conclusions Acalabrutinib successfully bridged most patients in this trial when given concurrently with axi-cel and safely maintained high CR rates. CRP and ferritin levels were typically only modestly elevated after cell infusion. Severe CRS was not observed and high-grade ICANS was uncommon."

CAR T-Cell Therapy • Clinical • Combination therapy • IO biomarker • P1/2 data • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Mediastinal Large B-Cell Lymphoma • IL6 • MYC

A randomized trial of ibrutinib and R-GDP prior to stem cell transplant in relapsed diffuse large B-cell lymphoma. (PubMed, Br J Haematol) - "In the LY.17 randomized phase II clinical trial, adults with relapsed and refractory diffuse large B-cell lymphoma treated with ibrutinib-R-GDP (IR-GDP) for up to three cycles had more documented bacterial and fungal infections, without improvement in overall response, compared with R-GDP. CR, complete response; DLBCL, diffuse large B-cell lymphoma; PD, progressive disease; PR, partial response; R/R, relapsed/refractory; SD, stable disease."

Journal • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation

Acalabrutinib Versus Ibrutinib in Previously Treated Chronic Lymphocytic Leukemia: Results of the First Randomized Phase III Trial. (PubMed, J Clin Oncol) - "In this first direct comparison of less versus more selective Bruton's tyrosine kinase inhibitors in CLL, acalabrutinib demonstrated noninferior PFS with fewer cardiovascular adverse events."

Clinical • Journal • P3 data • Atrial Fibrillation • Cardiovascular • Chronic Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Richter's Syndrome

Real-World Outcomes of Pirtobrutinib Versus Venetoclax After Covalent BTK Inhibitor Exposure in CLL/SLL (SOHO 2026) - "Adults with CLL/SLL previously exposed to a covalent BTK inhibitor, including ibrutinib, acalabrutinib, or zanubrutinib, were identified...Propensity score matching included demographics; prior BTK inhibitor exposure; prior rituximab and antineoplastic therapy; and baseline creatinine, hemoglobin, neutrophil count, platelet count, and albumin levels... In this large real-world matched analysis of patients with CLL/SLL previously exposed to covalent BTK inhibitors, pirtobrutinib showed comparable 12-month survival, infection risk, and early hematologic safety relative to venetoclax. In evolving treatment algorithms that now include noncovalent BTK inhibition after covalent BTK inhibitor exposure, these findings support pirtobrutinib as a practical sequencing option with outcomes similar to an established venetoclax-based approach. Rather than identifying a single preferred strategy, these data support individualized treatment selection based on prior therapy, comorbidity..."

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

Generational safety profiles of BTK inhibitors: adverse reaction signals and real-world evidence from the FAERS database. (PubMed, Front Med (Lausanne)) - "However, safety concerns remain regarding treatment-associated adverse events: first-generation ibrutinib has been associated with off-target adverse event profiles, second-generation agents (acalabrutinib and zanubrutinib) require further validation of long-term safety patterns, and the real-world safety characteristics of third-generation pirtobrutinib continue to be evaluated. This descriptive pharmacovigilance study identified distinct disproportionality reporting signal patterns for four BTK inhibitors based on FAERS data, providing potential signals for post-marketing safety surveillance. These findings should be interpreted as differences in reporting patterns."

HEOR • Journal • Real-world evidence • Atrial Fibrillation • Cardiovascular • Hematological Malignancies • Immunology • Infectious Disease • Oncology • Pain • Pneumonia • Respiratory Diseases