Jaypirca (pirtobrutinib) / Eli Lilly, Innovent Biologics, Nippon Shinyaku - LARVOL DELTA

311: Taking Up the Mantle: Novel Therapeutics in the Treatment of Mantle Cell Lymphoma (HOPA 2026) - "Additionally, this presentation will discuss advances in the treatment of relapsed/refractory MCL with novel agents such as chimeric antigen receptor (CAR) T-cell therapies, bispecific antibodies, and non-covalent BTK inhibitors, including a review of key efficacy outcomes, strategies for adverse event management, and considerations for treatment sequencing. UAN: 0465-0000-26-060-L01-P Knowledge or Application Based: Application Learning Objectives: Discuss the frontline use of Bruton's tyrosine kinase inhibitors (BTKis) in mantle cell lymphomaApply patient-specific factors to construct BTKi-based therapeutic plans for individuals with treatment-based therapeutic plans for individuals with treatment-naïve MCLEvaluate efficacy outcomes and toxicity management strategies forregimens incorporating pirtobrutinib, glofitamab, and/or chimeric antigenreceptor T-cell therapy (CAR-T) for treatment of relapsed/refractory MCLFormulate sequencing strategies for..."

Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma

NCE393TL: Reignite the Spark: Clinical Conversations about Jaypirca® (pirtobrutinib) (HOPA 2026) - "Reignite the Spark: Clinical Conversations about Jaypirca® (pirtobrutinib) Learn about the indication for Jayprica.Discuss the study design and results of a Phase 3 trial. This Non-CE Symposia program is sponsored by, and the speaker is presenting on behalf of Eli Lilly USA, LLC."

Clinical

EMT-like reprogramming drives drug-tolerant persister cell plasticity in mantle cell lymphoma via ribosome biogenesis (AACR 2026) - "Using pirtobrutinib (a clinically approved non-covalent BTKi), we established a reproducible, non-stochastic DTP cell model in MCL...Our work establishes that an EMT-like network, orchestrated by metabolic reprogramming and nucleolar SNAI1-driven ribosome biogenesis, governs DTP cell fate in MCL. Targeting this axis—particularly ribosome biogenesis—offers a transformative strategy to eradicate persister cells and overcome resistance to BTKi and CAR T-cell therapy."

Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • FBL • SNAI1

Comparative analysis: multiple generations of BTK inhibitors but not BCL-2 inhibitor venetoclax impair dendritic cell and T-cell function ​​​​​ (OeGHO-AHOP 2026) - "In this study, we analyzed and compared the effect of the leading BTKi ibrutinib, acalabrutinib, zanubrutinib, and pirtobrutinib, and the BCL-2i venetoclax on the phenotype and function of human dendritic cells and T-cells. Our data suggest that all tested BTKi exhibit an inhibitory effect on LPS-induced DC activation, while T-cell proliferation was impaired by pirtobrutinib in addition to ibrutinib. Knowledge of immunomodulatory effects will optimize therapy selection and improve patient safety."

IO biomarker • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Leukemia • Lymphoma • BCL2

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

Pirtobrutinib approved to treat chronic lymphocytic leukemia and small lymphocytic lymphoma. (PubMed, Am J Nurs) - No abstract available

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

Pirtobrutinib, a Highly Selective, Non-covalent (Reversible) BTKi in R/R Follicular Lymphoma: Phase 1/2 BRUIN Study. (PubMed, Blood Adv) - "Pirtobrutinib was well-tolerated with two patients (4.2%) discontinuing treatment due to AEs (one treatment-related) and four patients (8.3%) having dose reductions due to AEs (all treatment-related). Pirtobrutinib showed promising efficacy and was well tolerated in this cohort of heavily pre-treated patients with R/R FL warranting further investigation."

Journal • P1/2 data • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

Bridging the Gap: Pirtobrutinib for Treatment-Naïve Chronic Lymphatic Leukemia. (PubMed, J Clin Oncol) - No abstract available

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

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

A matching-adjusted indirect comparison of survival outcomes with pirtobrutinib (BRUIN) versus standard of care (SCHOLAR-2) in relapsed/refractory mantle cell lymphoma previously treated with a covalent Bruton tyrosine kinase inhibitor. (PubMed, Br J Haematol) - No abstract available

Journal • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology

Marginal Zone Lymphoma (ICKSH 2026) - "Bendamustine -rituximab demonstrates an ORR of ~93% and CR of ~81% in EMZL, with 5 -year PFS of ~8 0%. Lenalidomide - rituximab (R² ) offers an effective chemotherapy -free option with ORR of 93%, CR of 70%, and 5 - year OS of 96%...Zanubrutinib is now the pref erred agent based on the MAGNOLIA trial, demonstrating an ORR of 68%, CR of 26%, with favorable safety profile including low rates of atrial fibrillation (3%)...Emerging therapies include CAR -T cell therapy (axicabtagene ciloleucel showed ORR 77% in ZUMA -5), CD20×CD3 bispecific antibodies (mosunetuzumab, epcoritamab, glofitamab), non - covalent BTK inhibitors (pirtobrutinib), and antibody -drug conjugates...Key unmet needs include MZL -specific clinical trials, understanding of transformation biology, and development of novel targeted therapies. With the expanding therapeutic armamentarium, the treatment paradigm is shifting toward targeted, immune -based strategies, offering improved outcomes for..."

Atrial Fibrillation • Cardiovascular • Endocrine Disorders • Extranodal Marginal Zone Lymphoma • Hematological Malignancies • Hepatitis C • Hepatology • Immunology • Indolent Lymphoma • Infectious Disease • Lyme Disease • Lymphoma • Lymphoplasmacytic Lymphoma • Marginal Zone Lymphoma • Nodal Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Sjogren's Syndrome • Splenic Marginal Zone Lymphoma • Waldenstrom Macroglobulinemia • BIRC3 • CCND1 • CD19 • CD20 • CD5 • CD79A • CREBBP • EP300 • KMT2D • MALT1 • MME • MYD88 • NOTCH2 • TNFAIP3

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

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

BRUIN CLL-313: Randomized Phase III Trial of Pirtobrutinib Versus Bendamustine Plus Rituximab in Untreated Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. (PubMed, J Clin Oncol) - "Pirtobrutinib demonstrated superiority over BendaR in IRC-assessed PFS in treatment-naïve CLL/SLL. OS trends favored pirtobrutinib despite the study design allowing for crossover. Pirtobrutinib was well tolerated, consistent with its known safety profile, and more favorable than BendaR."

IO biomarker • Journal • P3 data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • IGH

Shifting clones: CLL evolution under pirtobrutinib treatment. (PubMed, Blood) - No abstract available

Journal

Pirtobrutinib in Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL): Final update from the Phase 1/2 BRUIN study (ASH 2025) - P1/2 | "Pirtobrutinib continues to demonstrate efficacy in pts with heavily pre-treated R/R MCL including boththose who previously received a cBTKi and those who were BTKi-naïve. The safety profile of pirtobrutinibremained favorable with a low-rate of dose reductions/discontinuations due to drug-related toxicity. Nonew safety signals were identified after up to 5 yrs of follow-up."

P1/2 data • Atrial Fibrillation • Bone Marrow Transplantation • Hematological Malignancies • Infectious Disease • Lymphoma • Mantle Cell Lymphoma • Neutropenia • Pulmonary Disease

High VGPR/CR rates with pirtobrutinib plus venetoclax in previously treated Waldenström macroglobulinemia: Results from a multicenter phase II study (ASH 2025) - P2 | "For the 27 MYD88Mut patients, the median number of previous therapies was 1 (range 1-3); 14 (52%) werepreviously exposed to a covalent BTK inhibitor, of whom 10 had progressed while on therapy, and 15(56%) had previous rituximab-containing regimens. Based on the statistical assumptions, the present prospective multicenter Phase II studyevaluating pirtobrutinib and venetoclax in previously treated WM has met its primary endpoint with aVGPR/CR rate of 56% in the 27 MYD88MUT patients who have completed 6 months on study. Limitedactivity was seen in MYD88WT patients. No unexpected toxicities were observed, and study therapy waswell tolerated."

Clinical • IO biomarker • P2 data • Cardiovascular • Febrile Neutropenia • Hematological Disorders • Infectious Disease • Lymphoma • Lymphoplasmacytic Lymphoma • Musculoskeletal Pain • Neutropenia • Novel Coronavirus Disease • Respiratory Diseases • Thrombocytopenia • Waldenstrom Macroglobulinemia • BCL2 • CXCR4 • MYD88 • TINCR • TP53

A comprehensive analysis of pirtobrutinib in Chinese patients with chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL): Results from the phase 3 study BRUIN CLL-321. (PubMed, Br J Haematol) - "In this heavily pretreated population, pirtobrutinib significantly improved progression-free survival (PFS) compared to investigator's choice (IC) of idelalisib/rituximab (IdelaR) or bendamustine/rituximab (BendaR). Pirtobrutinib showed a favourable safety profile, with fewer grade ≥3 treatment-emergent adverse events (36.8% vs. 93.3%) and serious adverse events (15.8% vs. 46.7%). These findings support pirtobrutinib as a clinically active and tolerable option for cBTKi-pretreated Chinese CLL/SLL population."

Journal • P3 data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

CLLRT2: A prospective, open-label, randomized, multicenter phase-III trial to evaluate the efficacy of pirtobrutinib and epcoritamab compared with R-(mini)-CHOP for treatment of patients with DLBCL-type Richter Transformation (clinicaltrialsregister.eu) - P2/3 | N=41 | Not yet recruiting | Sponsor: University Of Cologne

New P2/3 trial • Diffuse Large B Cell Lymphoma • Large B Cell Lymphoma • Lymphoma • Oncology • Richter's Syndrome

Pirtobrutinib vs ibrutinib in treatment-naïve and relapsed/refractory CLL/SLL: Results from the first randomized phase III study comparing a non-covalent and covalent BTK inhibitor (ASH 2025) - P3 | "In this first head-to-head study, in cBTKi-naïve CLL/SLL, including pts with treatment naïveCLL, pirtobrutinib demonstrated NI of ORR vs ibrutinib in both ITT and R/R populations. PFS, while not yetmature, trended in favor of pirtobrutinib, with the most pronounced effect in the TN population, whichhad the longest follow-up at this data cut."

Clinical • P3 data • Atrial Fibrillation • Chronic Lymphocytic Leukemia • Hematological Malignancies • Hypertension • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Small Lymphocytic Lymphoma • IGH

BUDGET IMPACT OF INTRODUCING PIRTOBRUTINIB AFTER COVALENT BRUTON TYROSINE KINASE INHIBITOR THERAPY IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC LYMPHOMA IN THE US (ISPOR 2026) - P3 | "OBJECTIVES: Pirtobrutinib improved progression-free survival and demonstrated favorable tolerability versus investigator's choice of idelalisib/rituximab or bendamustine/rituximab in covalent Bruton tyrosine kinase inhibitor (cBTKi) pretreated patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; BRUIN-CLL-321, NCT04666038). The introduction of pirtobrutinib as post-cBTKi therapy for patients with CLL/SLL resulted in minimal annual PMPM costs for both Medicare and commercial payers. This finding reflects the low number of eligible patients and is highly influenced by monthly acquisition costs and duration of pirtobrutinib therapy."

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

Pirtobrutinib at the Crossroads: Shaping Its Future Role in Chronic Lymphocytic Leukemia (CLL) Care. (PubMed, Eur J Haematol) - "In patients with cBTKi-pretreated relapsed/refractory (R/R) CLL, the BRUIN-CLL-321 trial demonstrated improved progression-free survival (PFS) and time to next treatment (TTNT) compared with idelalisib/rituximab or bendamustine/rituximab, accompanied by a favorable tolerability profile. Data from randomized phase III BRUIN-CLL-313 and BRUIN-CLL-314 trials demonstrate the superiority of pirtobrutinib over chemoimmunotherapy in untreated patients and non-inferiority to ibrutinib in untreated patients or in patients with R/R disease who had no prior exposure to cBTKis. These data are not sufficient to justify a change in clinical practice; however, they lay the groundwork for a potential future repositioning of pirtobrutinib from the treatment of R/R CLL to earlier lines of therapy. In this review, we address a range of current and prospective aspects of pirtobrutinib-based therapies: (1) the strengths and limitations of the trial datasets; (2) the biological rationale for..."

IO biomarker • Journal • Review • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • PLCG2

DIFFERENTIAL CARDIOVASCULAR SAFETY PROFILES OF IBRUTINIB AND NEXT-GENERATION BTK INHIBITORS: FAERS ANALYSIS 2012-2025 (ACC 2026) - "FAERS pharmacovigilance reveals consistent cardiotoxicity with Ibrutinib across 2012-2025, whereas newer BTK inhibitors exhibit fewer but emerging signals, emphasizing the need for ongoing surveillance."

Clinical • Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Malignancies • Myocardial Infarction • ROR1

NCCN Guidelines® Insights: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 2.2026. (PubMed, J Natl Compr Canc Netw) - "Pirtobrutinib (a noncovalent BTKi) and lisocabtagene maraleucel (CD19-directed CAR T-cell therapy) are newer options for relapsed or refractory disease after prior therapy with BTKi and BCL2i-contining regimens. Molecular analysis to determine whether there is clonal relationship between CLL/SLL and transformed diffuse large B-cell lymphoma is useful to select an appropriate treatment option. These NCCN Guideline Insights highlight significant updates to the NCCN Guidelines for the treatment of CLL/SLL and Richter transformation."

Clinical • Clinical guideline • Journal • NCCN guideline • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • Small Lymphocytic Lymphoma