On November 24, 2025 Eli Lilly and Company (NYSE: LLY) reported that data from studies of Jaypirca (pirtobrutinib), the first and only approved non-covalent (reversible) Bruton tyrosine kinase (BTK) inhibitor, will be presented at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, taking place Dec. 6-9 in Orlando, Florida.
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Key data presentations for Jaypirca include:
In an oral presentation, Lilly will share results from the BRUIN CLL-314 study, comparing pirtobrutinib to Imbruvica (ibrutinib), a covalent BTK inhibitor, in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL). Lilly previously announced that pirtobrutinib met the primary endpoint of response rate non-inferiority, favoring pirtobrutinib with a nominal P-value for superiority < 0.05. BRUIN CLL-314 is the first-ever head-to-head Phase 3 study versus a covalent BTK inhibitor to include treatment-naïve patients. These results were also selected to be highlighted in the ASH (Free ASH Whitepaper) Annual Meeting press program session on Dec. 7.
In a late-breaking oral presentation, Lilly will share results from the Phase 3 BRUIN CLL-313 study of pirtobrutinib versus chemoimmunotherapy in patients with treatment-naïve CLL/SLL without del(17p). Lilly previously announced the study met its primary endpoint, demonstrating a highly statistically significant and clinically meaningful improvement in progression-free survival with pirtobrutinib compared to chemoimmunotherapy. These results were also selected to be highlighted in the ASH (Free ASH Whitepaper) Annual Meeting press program session on Dec. 8.
In other oral and poster presentations, Lilly will share additional data from the Phase 1/2 BRUIN study in patients with relapsed or refractory CLL, mantle cell lymphoma (MCL) and Waldenström macroglobulinemia (WM). These long-term data include efficacy and safety results with approximately five years of follow-up.
In an oral presentation, results will be shared from an investigator-initiated Phase 2 study of time-limited treatment with a combination of pirtobrutinib, venetoclax, and obinutuzumab in treatment-naïve CLL.
"Building on our previous announcements of positive topline results for the Phase 3 BRUIN CLL-313 and CLL-314 studies, we are excited to share the full results at ASH (Free ASH Whitepaper)," said Jacob Van Naarden, executive vice president and president of Lilly Oncology. "Collectively, data from across the pirtobrutinib development program and investigator-led studies reinforce the medicine’s unique clinical profile and its potential role across treatment settings and B-cell malignancies."
A full list of abstract titles and viewing details are listed below:
Abstract Title
Author
Presentation
Type/#
Session Title
Session
Date/Time
(EST)
Pirtobrutinib in relapsed/refractory (R/R)
Waldenström macroglobulinemia (WM): Up
to 5 years of follow-up from the Phase 1/2
BRUIN study
Chan Cheah
Oral
Abstract
#226
623. Mantle Cell,
Follicular,
Waldenstrom’s,
and Other
Indolent B Cell
Lymphomas:
Clinical and
Epidemiological:
FL and WM
Saturday,
Dec. 6
2:45-3
p.m. EST
Real-world treatment patterns, patient
characteristics, and outcomes of cBTKi-based
therapies amongst a contemporary cohort of
patients with R/R MCL in the United States
Kami
Maddocks
Poster
Abstract
#2725
906. Outcomes
Research:
Lymphoid
Malignancies
Excluding Plasma
Cell Disorders:
Poster I
Saturday,
Dec. 6
5:30-7:30
p.m. EST
Real-world characteristics, treatment
patterns and outcomes of patients with
mantle cell lymphoma (MCL) after receiving
covalent Bruton tyrosine kinase inhibitors
(cBTKi) in China
Yuqin Song
Poster
Abstract
#2704
906. Outcomes
Research:
Lymphoid
Malignancies
Excluding Plasma
Cell Disorders:
Poster I
Saturday,
Dec. 6
5:30-7:30
p.m. EST
Pirtobrutinib in post-cBTKi CLL/SLL: Final
update from the Phase 1/2 BRUIN study with
more than 5 years follow-up
William
Wierda
Poster
Abstract
#2115
642. Chronic
Lymphocytic
Leukemia: Clinical
and
Epidemiological:
Poster I
Saturday,
Dec. 6
5:30-7:30
p.m. EST
Pirtobrutinib in relapsed/refractory (R/R)
mantle cell lymphoma (MCL): final update
from the Phase 1/2 BRUIN study
Michael
Wang
Oral
Abstract
#665
623. Mantle Cell,
Follicular,
Waldenstrom’s,
and Other
Indolent B Cell
Lymphomas:
Clinical and
Epidemiological –
Novel Treatments
for and Insights
into Mantle Cell
Lymphoma
Sunday,
Dec. 7
5:30-5:45
p.m. EST
Pirtobrutinib vs ibrutinib in treatment-naïve
and relapsed/refractory CLL/SLL: Results
from the first randomized Phase 3
study comparing a non-covalent and
covalent BTK inhibitor
Jennifer
Woyach
Oral
Abstract
#683
642. Chronic
Lymphocytic
Leukemia: Clinical
and
Epidemiological:
Frontline
Treatment
Strategies for CLL
Sunday,
Dec. 7
5:30-5:45
p.m. EST
Efficacy of pirtobrutinib monotherapy in
treatment-naïve chronic lymphocytic
leukemia: A Bayesian network meta-analysis
of randomized controlled trials
Toby Eyre
Poster
Abstract
#5684
642. Chronic
Lymphocytic
Leukemia: Clinical
and
Epidemiological:
Poster III
Monday,
Dec. 8
6-8
p.m. EST
Pirtobrutinib outcomes in second-line (2L)
chronic lymphocytic leukemia/small
lymphocytic lymphoma (CLL/SLL) after first-
line (1L) cBTKi therapy: A pooled analysis
from the BRUIN LOXO-BTK-18001 and BRUIN
CLL-321 studies
Toby Eyre
Poster
Abstract
#5670
642. Chronic
Lymphocytic
Leukemia: Clinical
and
Epidemiological:
Poster III
Monday,
Dec. 8
6-8
p.m. EST
Pirtobrutinib vs bendamustine plus rituximab
(BR) in patients with CLL/SLL: First results
from a randomized Phase 3 study examining
a non-covalent BTK inhibitor in untreated
patients
Wojciech
Jurczak
Oral
Abstract
#LBA-3
Late-Breaking
Abstracts Session
Tuesday,
Dec. 9
8-8:15
a.m. EST
Investigator-Initiated
Pirtobrutinib, venetoclax, and obinutuzumab
for patients with Richter transformation: A
Phase 2 trial
Nitin Jain
Oral
Abstract
#89
642. Chronic
Lymphocytic
Leukemia: Clinical
and
Epidemiological:
Treatment of CLL
in Relapse and in
Richter
Transformation
Saturday,
Dec. 6
10:30-10:45
a.m. EST
High VGPR/CR rates with pirtobrutinib plus
venetoclax in previously treated
Waldenström macroglobulinemia: Results
from a multicenter Phase 2 study
Jorge Castillo
Oral
Abstract
#225
623. Mantle Cell,
Follicular,
Waldenstrom’s,
and Other
Indolent B Cell
Lymphomas:
Clinical and
Epidemiological:
FL and WM
Saturday,
Dec. 6
2:30-2:45
p.m. EST
Time-limited pirtobrutinib, venetoclax, and
obinutuzumab combination in first-line
chronic lymphocytic leukemia
Nitin Jain
Oral
Abstract
#680
642. Chronic
Lymphocytic
Leukemia: Clinical and
Epidemiological:
Frontline
Treatment
Strategies for CLL
Sunday,
Dec. 7
4:45-5
p.m. EST
Pirtobrutinib, a non-covalent BTK inhibitor,
enhances T-cell anti-tumor immunity in
chronic lymphocytic leukemia (CLL)
Sonia
Rodriguez-
Rodriguez
Poster
Abstract
#3878
641. Chronic
Lymphocytic
Leukemia: Basic
and
Translational:
Poster II
Sunday,
Dec. 7
6-8
p.m. EST
Pirtobrutinib versus usual care for patients
with Richter transformation of chronic
lymphocytic leukemia: Inverse probability of
treatment weighting-based analysis of BRUIN
trial and mayo observational cohort
Yucai Wang
Poster
Abstract
#5673
642. Chronic
Lymphocytic
Leukemia: Clinical
and
Epidemiological:
Poster III
Monday,
Dec. 8
6-8
p.m. EST
About Jaypirca (pirtobrutinib)
Jaypirca (pirtobrutinib, formerly known as LOXO-305) (pronounced jay-pihr-kaa) is a highly selective (300 times more selective for BTK versus 98% of other kinases tested in preclinical studies), non-covalent (reversible) inhibitor of the enzyme BTK.1 BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL).2,3 Jaypirca is a U.S. FDA-approved oral prescription medicine, 100 mg or 50 mg tablets taken as a once-daily 200 mg dose with or without food until disease progression or unacceptable toxicity.
INDICATIONS FOR JAYPIRCA (pirtobrutinib)
Jaypirca is a kinase inhibitor indicated for the treatment of
Adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor.
Adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.
These indications are approved under accelerated approval based on response rate. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial.
IMPORTANT SAFETY INFORMATION FOR JAYPIRCA (pirtobrutinib)
Infections: Fatal and serious infections (including bacterial, viral, fungal) and opportunistic infections occurred in Jaypirca-treated patients. In a clinical trial, Grade ≥3 infections occurred in 24% of patients with hematologic malignancies, most commonly pneumonia (14%); fatal infections occurred (4.4%). Sepsis (6%) and febrile neutropenia (4%) occurred. In patients with CLL/SLL, Grade ≥3 infections occurred (32%), with fatal infections occurring in 8%. Opportunistic infections included Pneumocystis jirovecii pneumonia and fungal infection. Consider prophylaxis, including vaccinations and antimicrobial prophylaxis, in patients at increased risk for infection, including opportunistic infections. Monitor patients for signs and symptoms, evaluate promptly, and treat appropriately. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.
Hemorrhage: Fatal and serious hemorrhage has occurred with Jaypirca. Major hemorrhage (Grade ≥3 bleeding or any central nervous system bleeding) occurred in 3% of patients, including gastrointestinal hemorrhage; fatal hemorrhage occurred (0.3%). Bleeding of any grade, excluding bruising and petechiae, occurred (17%). Major hemorrhage occurred in patients taking Jaypirca with (0.7%) and without (2.3%) antithrombotic agents. Consider risks/benefits of co-administering antithrombotic agents with Jaypirca. Monitor patients for signs of bleeding. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca. Consider benefit/risk of withholding Jaypirca 3-7 days pre- and post-surgery depending on type of surgery and bleeding risk.
Cytopenias: Jaypirca can cause cytopenias, including neutropenia, thrombocytopenia, and anemia. In a clinical trial, Grade 3 or 4 cytopenias, including decreased neutrophils (26%), decreased platelets (12%), and decreased hemoglobin (12%), developed in Jaypirca-treated patients. Grade 4 decreased neutrophils (14%) and Grade 4 decreased platelets (6%) developed. Monitor complete blood counts regularly during treatment. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.
Cardiac Arrhythmias: Cardiac arrhythmias occurred in patients who received Jaypirca. In a clinical trial of patients with hematologic malignancies, atrial fibrillation or flutter were reported in 3.2% of Jaypirca-treated patients, with Grade 3 or 4 atrial fibrillation or flutter in 1.5%. Other serious cardiac arrhythmias such as supraventricular tachycardia and cardiac arrest occurred (0.5%). Patients with cardiac risk factors such as hypertension or previous arrhythmias may be at increased risk. Monitor for signs and symptoms of arrhythmias (e.g., palpitations, dizziness, syncope, dyspnea) and manage appropriately. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.
Second Primary Malignancies: Second primary malignancies, including non-skin carcinomas, developed in 9% of Jaypirca-treated patients. The most frequent malignancy was non-melanoma skin cancer (4.6%). Other second primary malignancies included solid tumors (including genitourinary and breast cancers) and melanoma. Advise patients to use sun protection and monitor for development of second primary malignancies.
Hepatotoxicity, Including Drug-Induced Liver Injury (DILI): Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of DILI, has occurred in patients treated with BTK inhibitors, including Jaypirca. Evaluate bilirubin and transaminases at baseline and throughout Jaypirca treatment. For patients who develop abnormal liver tests after Jaypirca, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold Jaypirca. Upon confirmation of DILI, discontinue Jaypirca.
Embryo-Fetal Toxicity: Jaypirca can cause fetal harm in pregnant women. Administration of pirtobrutinib to pregnant rats caused embryo-fetal toxicity, including embryo-fetal mortality and malformations at maternal exposures (AUC) approximately 3-times the recommended 200 mg/day dose. Advise pregnant women of potential fetal risk and females of reproductive potential to use effective contraception during treatment and for one week after last dose.
Adverse Reactions (ARs) in Patients Who Received Jaypirca
The most common (≥20%) ARs in the BRUIN pooled safety population of patients with hematologic malignancies (n=593) were decreased neutrophil count (46%), decreased hemoglobin (39%), fatigue (32%), decreased lymphocyte count (31%), musculoskeletal pain (30%), decreased platelet count (29%), diarrhea (24%), COVID-19 (22%), bruising (21%), cough (20%).
Mantle Cell Lymphoma
Serious ARs occurred in 38% of patients. Serious ARs occurring in ≥2% of patients were pneumonia (14%), COVID-19 (4.7%), musculoskeletal pain (3.9%), hemorrhage (2.3%), pleural effusion (2.3%), and sepsis (2.3%). Fatal ARs within 28 days of last Jaypirca dose occurred in 7% of patients, most commonly due to infections (4.7%), including COVID-19 (3.1% of all patients).
Dose Modifications and Discontinuations: ARs led to dose reductions in 4.7%, treatment interruption in 32%, and permanent discontinuation of Jaypirca in 9% of patients. ARs resulting in dosage modification in >5% of patients included pneumonia and neutropenia. ARs resulting in permanent discontinuation in >1% of patients included pneumonia.
Most common ARs (≥15%), excluding laboratory terms (all Grades %; Grade 3-4 %): fatigue (29; 1.6), musculoskeletal pain (27; 3.9), diarrhea (19; -), edema (18; 0.8), dyspnea (17; 2.3), pneumonia (16; 14), bruising (16; -).
Select Laboratory Abnormalities (all Grades %; Grade 3 or 4 %) that Worsened from Baseline in ≥10% of Patients: hemoglobin decreased (42; 9), platelet count decreased (39; 14), neutrophil count decreased (36; 16), lymphocyte count decreased (32; 15), creatinine increased (30; 1.6), calcium decreased (19; 1.6), AST increased (17; 1.6), potassium decreased (13; 1.6), sodium decreased (13; -), lipase increased (12; 4.4), alkaline phosphatase increased (11; -), ALT increased (11; 1.6), potassium increased (11; 0.8). Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (10), platelets decreased (7), lymphocytes decreased (6).
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Serious ARs occurred in 56% of patients. Serious ARs occurring in ≥5% of patients were pneumonia (18%), COVID-19 (9%), sepsis (7%), and febrile neutropenia (7%). Fatal ARs within 28 days of last Jaypirca dose occurred in 11% of patients, most commonly due to infections (10%), including sepsis (5%) and COVID-19 (2.7%).
Dose Modifications and Discontinuations: ARs led to dose reductions in 3.6%, treatment interruption in 42%, and permanent discontinuation of Jaypirca in 9% of patients. ARs resulting in dose reductions in >1% included neutropenia; treatment interruptions in >5% of patients included pneumonia, neutropenia, febrile neutropenia, and COVID-19; permanent discontinuation in >1% of patients included second primary malignancy, COVID-19, and sepsis.
Most common ARs (≥20%), excluding laboratory terms (all Grades %; Grade 3-4 %): fatigue (36; 2.7), bruising (36; -), cough (33; -), musculoskeletal pain (32; 0.9), COVID-19 (28; 7), pneumonia (27; 16), diarrhea (26; -), abdominal pain (25; 2.7), dyspnea (22; 2.7), hemorrhage (22; 2.7), edema (21; -), nausea (21; -), pyrexia (20; 2.7), headache (20; 0.9).
Select Laboratory Abnormalities (all Grades %; Grade 3 or 4 %) that Worsened from Baseline in ≥20% of Patients: neutrophil count decreased (63; 45), hemoglobin decreased (48; 19), calcium decreased (40; 2.8), platelet count decreased (30; 15), sodium decreased (30; -), lymphocyte count decreased (23; 8), ALT increased (23; 2.8), AST increased (23; 1.9), creatinine increased (23; -), lipase increased (21; 7), alkaline phosphatase increased (21; -). Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (23).
Drug Interactions
Strong CYP3A Inhibitors: Concomitant use with Jaypirca increased pirtobrutinib systemic exposure, which may increase risk of Jaypirca ARs. Avoid use of strong CYP3A inhibitors with Jaypirca. If concomitant use is unavoidable, reduce Jaypirca dosage according to approved labeling.
Strong or Moderate CYP3A Inducers: Concomitant use with Jaypirca decreased pirtobrutinib systemic exposure, which may reduce Jaypirca efficacy. Avoid concomitant use of Jaypirca with strong or moderate CYP3A inducers. If concomitant use with moderate CYP3A inducers is unavoidable, increase Jaypirca dosage according to approved labeling.
Sensitive CYP2C8, CYP2C19, CYP3A, P-gp, or BCRP Substrates: Concomitant use with Jaypirca increased their plasma concentrations, which may increase risk of adverse reactions related to these substrates for drugs that are sensitive to minimal concentration changes. Follow recommendations for these sensitive substrates in their approved labeling.
Use in Special Populations
Pregnancy and Lactation: Due to potential for Jaypirca to cause fetal harm, verify pregnancy status in females of reproductive potential prior to starting Jaypirca and advise use of effective contraception during treatment and for one week after last dose. Presence of pirtobrutinib in human milk is unknown. Advise women not to breastfeed while taking Jaypirca and for one week after last dose.
Geriatric Use: In the pooled safety population of patients with hematologic malignancies, patients aged ≥65 years experienced higher rates of Grade ≥3 ARs and serious ARs compared to patients <65 years of age.
Renal Impairment: Severe renal impairment increases pirtobrutinib exposure. Reduce Jaypirca dosage in patients with severe renal impairment according to approved labeling.
PT HCP ISI MCL_CLL AA JUN2024
Please see Prescribing Information and Patient Information for Jaypirca.
(Press release, Eli Lilly, NOV 24, 2025, View Source [SID1234660894])