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

Pirtobrutinib, venetoclax, and obinutuzumab for patients with richter transformation: A phase 2 trial (ASH 2025) - P2 | "Threepts had no response (1 pt with previously untreated RT who received venetoclax +obinutuzumab for CLL; 1 pt with prior BR and Ibrutinib + obinutuzumab for CLL, and prior atezolizumab + venetoclax +obinutuzumab, and R-CHOP + venetoclax for RT; 1 pt with no prior CLL therapy and R-EPOCH forRT).Two of the responding pts underwent consolidative allo-SCT. We report results of combined pirtobrutinib, venetoclax, and obinutuzumab in ptswith untreated or R/R RT. We observed an ORR rate of 67% and a 12-month EFS and OS rates of73% and 82%, respectively."

Clinical • IO biomarker • P2 data • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Richter's Syndrome • TP53

GELTAMO-IMCL-2015: Multicentric phase II trial to evaluate the efficacy and safety of Ibrutinib in combination with rituximab in patients with indolent clinical forms of Mantle Cell Lymphoma. (clinicaltrialsregister.eu) - P1/2 | N=50 | Active, not recruiting | Sponsor: Fundacion Geltamo | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology

BCR SIGNALING MODULATES EXPRESSION OF GLYCOSYLTRANSFERASES INVOLVED IN O-GLYCOSYLATION PATHWAYS IN PRIMARY TONSILLAR IGA+ CELLS FROM PATIENTS WITH IGA NEPHROPATHY (ISN-WCN 2026) - "Our findings suggest that Bruton's tyrosine kinase (Btk), a key component of BCR signaling, modulates expression of glycosyltransferases involved in O-glycosylation pathways.Methods Immortalized IgA1-producing cell lines derived from peripheral blood of IgAN patients and healthy controls (HC) were treated with a Btk inhibitor (ibrutinib)...These findings suggest that both BCR and Btk affect glycosylation phenotypes of IgA-producing cells. Thus, Btk may represent a novel therapeutic target in IgAN."

Clinical • IO biomarker • Glomerulonephritis • IgA Nephropathy • Infectious Disease • Otorhinolaryngology • Renal Disease • GALNT2

RENAL REMISSION OF IGM-TYPE PROLIFERATIVE GLOMERULONEPHRITIS WITH MONOCLONAL IMMUNOGLOBULIN DEPOSITS FOLLOWING TREATMENT FOR MANTLE CELL LYMPHOMA (ISN-WCN 2026) - "This case highlights the importance of considering MGRS-related glomerulonephritis, in addition to drug-induced injury, when evaluating renal impairment in lymphoma patients.Conclusion We describe a rare case of IgM-type PGNMID associated with MCL during ibrutinib therapy. Detailed pathological assessment is essential to distinguish lymphoma-related renal disease from drug-induced injury in patients receiving molecularly targeted agents for B-cell malignancies."

Clinical • B Cell Lymphoma • Cardiovascular • Glomerulonephritis • Hematological Malignancies • Hypertension • Lupus Nephritis • Lymphoma • Mantle Cell Lymphoma • Monoclonal Gammopathy • Nephrology • Peptic Ulcer

Noncanonical β-Amino Esters and Amides via Direct Asymmetric Reductive Amination of α,α-Disubstituted β-Ketoesters and Amides. (PubMed, Org Lett) - "High-throughput experimentation was utilized to identify a commercial ruthenium BINAP complex as an optimal catalyst for this transformation and counterion effects were critical for enabling the chemoselective reduction in this DARA strategy. The protocol was employed to synthesize a variety of highly substituted noncanonical β-amino esters and amides in good yields and excellent enantioselectivities. An intermolecular functional group tolerance study revealed that many Lewis basic functionalities are tolerated under reaction conditions and mechanistic insight was gained from reaction profile monitoring, isotopic labeling experiments, precatalyst poisoning studies, and ketone/imine equilibrium experiments."

Journal • Novel Coronavirus Disease

Cardiac Safety Profiles of First-Generation vs. Second-Generation BTK Inhibitors: A Meta-Analysis. (PubMed, Oncologist) - "Second-generation BTKi may provide a more favorable cardiovascular safety profile than ibrutinib, resulting in fewer key cardiac events and less treatment-limiting toxicity. These findings should inform clinical decision-making, especially for patients with increased risk for cardiovascular disease."

Journal • Retrospective data • Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Heart Failure • Oncology

Zanubrutinib is well tolerated and effective in CLL/SLL patients intolerant of ibrutinib/acalabrutinib: Updated results. (PubMed, Blood Adv) - P2 | "These data demonstrate that patients intolerant of ibrutinib/acalabrutinib may benefit from switching to zanubrutinib therapy. ClinicalTrials.gov: NCT04116437."

Journal • Chronic Lymphocytic Leukemia • Fatigue • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • Small Lymphocytic Lymphoma

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

Outcomes following transition from ibrutinib to zanubrutinib in patients with Waldenström macroglobulinemia from ASPEN. (PubMed, Blood Adv) - P3 | "Long-term follow-up is ongoing. Registration: NCT03053440, NCT04170283."

Journal • Hematological Disorders • Hematological Malignancies • Lymphoma • Lymphoplasmacytic Lymphoma • Oncology • Waldenstrom Macroglobulinemia • MYD88

Phase I/II study of acalabrutinib, venetoclax, and obinutuzumab in patients with relapsed/refractory and previously untreated Mantle Cell Lymphoma (MAVO) (ASH 2025) - P1/2 | "Triplet combinations of the BTK inhibitors ibrutinib orzanubrutinib, venetoclax (V), and obinutuzumab (O) have demonstrated efficacy in MCL, includingTP53-aberrant disease (Le Gouill, Blood 2021; Kumar, Blood 2024). The primary endpoint of TN cohort B was met,and the estimated 2 yr PFS and OS in the 17 TP53 mutated pts compare favorably with alternativeregimens. Based on this data, the study will expand to include an additional 16 TP53 mutated pts."

Clinical • P1/2 data • Atrial Fibrillation • Cardiovascular • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Mantle Cell Lymphoma • Neutropenia • Thrombocytopenia • 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

Venetoclax and ibrutinib induces durable clinical responses in marginal zone lymphoma. (PubMed, Blood Adv) - P2 | "Durable, ongoing CR was observed in MRD negative patients. Trial registered at www.clinicaltrials.gov as NCT02471391."

Journal • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Oncology

Final Report of a Phase II Study of Ibrutinib and Venetoclax in Previously Untreated Waldenström Macroglobulinemia. (PubMed, Am J Hematol) - "Given the deep and durable responses seen in this study, concurrent BTK and BCL-2 inhibition warrants further development in WM. TP53 mutations emerged as an adverse factor in WM in this combination study."

IO biomarker • Journal • P2 data • Cardiovascular • Hematological Disorders • Lymphoma • Lymphoplasmacytic Lymphoma • Waldenstrom Macroglobulinemia • CXCR4 • MYD88

Precision targeting of BTK in chronic lymphocytic leukemia: computational insights into structural dynamics and the influence of mutations on BTK inhibitors through QM and MM studies. (PubMed, J Biomol Struct Dyn) - "Density functional theory-based local and global reactivity descriptors identified nucleophilic and electrophilic hotspots within the inhibitors, with nitrogen atoms in pirtobrutinib, zanubrutinib, and spebrutinib displaying pronounced nucleophilic potential, suggesting a key role in stabilizing interactions within the BTK active site. Molecular docking analyses revealed that these inhibitors maintained strong binding affinities across multiple BTK mutants, frequently exceeding that of ibrutinib...Binding free-energy calculations further supported these observations, with several mutant complexes demonstrating enhanced affinities relative to the wild type. Collectively, these findings highlight structurally resilient inhibitors capable of overcoming compound mutation-driven resistance and underscore the importance of BTK mutational profiling in guiding precision therapeutic strategies for BTK-driven malignancies."

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

Dual inhibition of AURKA and ERBB overcomes resistance to PI3K/BTK/BCL2 inhibitors in marginal zone lymphoma models (AACR 2026) - "Here, we evaluated the antitumor activity and mechanisms of alisertib and neratinib, alone or combined with the BTK inhibitor ibrutinib, in MZL models with acquired resistance to PI3K/BTK/BCL2 inhibitors. MZL cell lines Karpas1718 and VL51, along with their derivatives resistant to PI3K/BTK/BCL2 inhibitors (Arribas et al., 2022; 2024; 2025), were treated with alisertib, neratinib, and ibrutinib individually or in combination. Dual inhibition of AURKA and ERBB pathways with alisertib and neratinib synergizes with BTK blockade to overcome resistance to multiple targeted therapies in MZL. Given the clinical availability of neratinib and emerging safety data for alisertib, these findings highlight a therapeutically actionable strategy that could be rapidly advanced into early-phase trials for relapsed/refractory MZL. This combination approach may expand treatment options for patients with limited responses to current PI3K, BTK, or BCL2 inhibitors."

B Cell Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • AURKA • MCL1 • PLK1

Large-scale drug screening identifies clinically actionable combinations to overcome BTK/PI3K inhibitor resistance in marginal zone lymphoma (AACR 2026) - "Here, we present data from a large pharmacological screen involving over 3,500 compounds in 2 MZL models with secondary resistance to BTK/PI3Ki, developed through prolonged exposure to idelalisib (Arribas 2022) or ibrutinib (Arribas 2025).Methods...Adding the alisertib (AURKAi), rigosertib (PLKi), fimepinostat (PI3K/HDACi), lanatoside-C (Na+K+ATPase), astragalin (apoptosis), astragaloside-I (WNT) and oridonin (AKT) was of benefit (additivity or synergism) in both parental and resistant cells.Conclusions...Several clinically advanced agents—particularly PAK4/NAMPT, AURKA, WNT, and Na⁺/K⁺-ATPase inhibitors—enhanced or restored the activity of BTKi/PI3Ki. These findings highlight new therapeutic strategies for relapsed/refractory MZL and support clinical evaluation of targeted combinations to overcome acquired resistance."

Clinical • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Oncology • AURKA • NAMPT

Ibrutinib plus venetoclax in relapsed or refractory mantle cell lymphoma (SYMPATICO): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. (PubMed, Lancet Oncol) - P3 | "The combination of ibrutinib-venetoclax significantly improved progression-free survival compared with ibrutinib-placebo in patients with relapsed or refractory MCL. The safety profile was consistent with known safety profiles of the individual drugs. These findings suggest a positive benefit-risk profile for ibrutinib-venetoclax treatment."

Clinical • Journal • P3 data • Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Mantle Cell Lymphoma • Neutropenia • Novel Coronavirus Disease • Oncology • Pneumonia • Respiratory Diseases • Thrombocytopenia

THE TRIPLE COMBINATION OF VENETOCLAX-IBRUTINIB-OBINUTUZUMAB PROLONGS PROGRESSION-FREE SURVIVAL COMPARED TO VENETOCLAX-CD20-ANTIBODY COMBINATIONS AND CHEMOIMMUNOTHERAPY IN TREATMENT-NAIVE CHRONIC LYMPHOCYTIC LEUKEMIA: FINAL ANALYSIS FROM THE PHASE 3 GAIA/CLL13 TRIAL (EHA 2025) - "Background: The GAIA/CLL13 trial showed superior progression-free survival (PFS) for venetoclax-obinutuzumab (GV) and GV + ibrutinib (GIV) compared to chemoimmunotherapy (CIT) and venetoclax-rituximab (RV) in fit treatment-naive patients (pts) with CLL and without TP53 aberrations. With more than 5 years of follow-up of this four-arm randomized intergroup trial the triple therapy with GIV now also demonstrates longer PFS compared to GV likely driven by the difference in pts with unmutated IGHV. PFS continues to be superior for GV and GIV compared to CIT and RV, but no OS differences were observed between treatment groups. In conclusion, GIV prolongs PFS compared to the widely used standard of GV, but factors like tolerability (Fürstenau et al."

IO biomarker • P3 data • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Genetic Disorders • Hematological Malignancies • Hodgkin Lymphoma • Infectious Disease • Leukemia • Lymphoma • Non-melanoma Skin Cancer • Pneumonia • Respiratory Diseases • Richter's Syndrome • Skin Cancer • Solid Tumor • IGH • TP53

Rituxan/Bendamustine/PCI-32765 in Relapsed DLBCL, MCL, or Indolent Non-Hodgkin's Lymphoma (clinicaltrials.gov) - P1 | N=48 | Active, not recruiting | Sponsor: Kami Maddocks, MD | Trial completion date: Oct 2025 ➔ Sep 2026 | Trial primary completion date: Oct 2025 ➔ Jul 2026

Trial completion date • Trial primary completion date • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Extranodal Marginal Zone Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Nodal Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Splenic Marginal Zone Lymphoma • Waldenstrom Macroglobulinemia

Disseminated Nocardia cyriacigeorgica infection presenting as necrotising epididymo-orchitis and testicular abscess in an immunocompromised patient on ibrutinib (ESCMID Global 2026) - No abstract available

Clinical • Infectious Disease

NOVEL THERAPIES FOR RELAPSED/REFRACTORY MANTLE CELL LYMPHOMA POST BRUTON'S TYROSINE KINASE INHIBITOR: A TARGETED LITERATURE REVIEW (ISPOR 2026) - "Five ongoing studies without outcomes reported are evaluating ixazomib, odronextamab, and rocbrutinib...Drugs evaluated included antibody-drug conjugates (ADCs) (zilovertamab, polatuzumab + obinutuzumab), bispecific antibodies (BsAbs) (mosunetuzumab-based, glofitamab), noncovalent BTKi (ncBTKi) (pirtobrutinib), chimeric antigen receptor T-cell (CAR-T) (brexucabtagene, lisocabtagene, tisagenlecleucel), ViPOR regimen (venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide), proteasome inhibitor (PI) (carfilzomib)... Preliminary data indicate promising but heterogenous results within drug classes. Interpretation is limited by small sample sizes and differences in study design, underscoring the need for further investigation in this area of high unmet need."

Review • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma

Cerebral histoplasmosis in a patient under ibrutinib therapy: diagnostic challenges and paradoxical radiological progression after treatment initiation (ESCMID Global 2026) - No abstract available

Clinical

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

Pirtobrutinib vs bendamustine plus rituximab (BR) in patients with CLL/SLL: First results from a randomized phase III study Examining a non-covalent BTK inhibitor in untreated patients (ASH 2025) - P3 | "A recent headto-head phase 3 trial (BRUIN CLL-314 presented at this meeting, ASH abstract 25-2587; NCT05254743) showed a favorable overall response rate (ORR) and a positive PFS trend with pirtobrutinib compared to the cBTKi ibrutinib in a subset of pts with treatment-naïve CLL. In BRUIN CLL-313, pirtobrutinib significantly improved IRC-assessed PFS versus BR for pts with treatment-naïve CLL/SLL with one of the largest treatment effects ever observed for a single-agent BTKi against this comparator. Pirtobrutinib was well tolerated, consistent with its known safety profile, with low rates of discontinuation and atrial fibrillation/flutter. While OS data remained immature, a notable trend favoring pirtobrutinib was observed, despite 52.9% of BR pts crossing over to receive pirtobrutinib after PD."

Clinical • Late-breaking abstract • P3 data • Atrial Fibrillation • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Richter's Syndrome • Small Lymphocytic Lymphoma • IGH

Pirtobrutinib Versus Ibrutinib in Treatment-Naïve and Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. (PubMed, J Clin Oncol) - "Pirtobrutinib demonstrated NI of ORR versus ibrutinib, with a favorable early PFS trend, particularly in TN patients, and a favorable safety profile including low rates of atrial fibrillation and hypertension."

Journal • Atrial Fibrillation • Cardiovascular • Chronic Lymphocytic Leukemia • Hematological Malignancies • Hypertension • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma