Skip to main content
This site is intended only for U.S. Healthcare Providers
Fireworks with a black background

MCL Efficacy

Overall Response Rate
Duration of Response
Study design

Jaypirca may be appropriate for patients with R/R MCL who initially responded to second-line BTK inhibitors but are showing signs of progression1

In patients with R/R MCL previously treated with a BTK inhibitor (n=120), responses were consistent with longer follow-up1,2

CR rate increased from 13% to 16% in the updated analysis1,2

The primary endpoint in the initial analysis was ORR, which included patients with a best response of CR or PR and was assessed by IRC using 2014 Lugano criteria.1

The updated post-hoc analysis (median 11-month study follow-up) has not been reviewed by the FDA and is not included in the Prescribing Information for Jaypirca.3

*PET-CT scans were utilized in response assessments (in 45% of patients), with the remainder being assessed by CT scans only.2
†ORR using CT scan-based assessments in all patients was 49% (95% CI: 40, 58) and CR rate was 25%.2
‡PET-CT scans were utilized in response assessments (in 41% of patients), with the remainder being assessed by CT scans only.1
§ORR using CT scan-based assessments in all patients was 48% (95% CI: 38, 57) and CR rate was 13%.1
||Study follow-up is measured from first dose to last known date to be alive or study exit.
Due to rounding, percentages may not reflect the absolute figures.

BTK=Bruton’s tyrosine kinase; CI=confidence interval; CR=complete response; CT=computed tomography; IRC=independent review committee; MCL=mantle cell lymphoma; ORR=overall response rate; PET=positron emission tomography; PR=partial response; R/R=relapsed or refractory.

Explore the trial design arrowRight Arrow Right

SELECT IMPORTANT SAFETY INFORMATION

Hemorrhage: Fatal and serious hemorrhage has occurred with Jaypirca. Across clinical trials, major hemorrhage occurred (2.6%), including gastrointestinal hemorrhage; fatal hemorrhage occurred (0.3%). Bleeding of any grade, excluding bruising and petechiae, occurred (16%). Major hemorrhage occurred when taking Jaypirca with (2.0%) and without (0.6%) antithrombotic agents. Consider risks/benefits of co-administering antithrombotic agents with Jaypirca and of withholding Jaypirca for 3-7 days pre- and post-surgery. Monitor for signs of bleeding and reduce dose, temporarily withhold, or permanently discontinue Jaypirca, based on severity.

In patients who responded (n=60)1,3,5

Duration of response with Jaypirca

11-month median study follow-up3#

Updated Analysis: DoR (n=60)5**††‡‡

Updated post-hoc analysis has not been reviewed by the FDA and is not included in the Prescribing Information for Jaypirca.

  • 32 of 60 responders had not progressed or died prior to data cutoff (censored)5,6
  • Median DoR was 17.6 months** (95% CI: 7.4, 25.3) with a median follow-up for DoR of 9.2 months5††‡‡§§

Initial Analysis (n=60)1

  • At 6 months, 65% of responders were still responding (95% CI: 50, 77)1
  • 36 of 60 responders had not progressed or died prior to data cutoff (censored)1,6
  • Median DoR was 8.3 months** (95% CI: 5.7, NE) with a median follow-up for DoR of 7.3 months1††‡‡§§

#Study follow-up is measured from first dose to last known date to be alive or study exit.
**Based on Kaplan-Meier estimation.1,5
††DoR was calculated for patients who achieved a response of PR or better and was defined as the time from first evidence of response to progression or death from any cause.6
‡‡The primary endpoint was ORR. Efficacy was based on patients with R/R MCL previously treated with a BTK inhibitor.1
§§DoR follow-up is measured from initial response to progression, death, or last adequate disease assessment in the absence of progression or death. Participants were censored at progression or death, according to the reverse Kaplan-Meier method.

NE=not estimable.

SELECT IMPORTANT SAFETY INFORMATION

Cytopenias: Jaypirca can cause cytopenias, including neutropenia, thrombocytopenia, and anemia. Across clinical trials, Grade 3 or 4 cytopenias, including decreased neutrophils (27%), decreased platelets (13%), and decreased hemoglobin (11%), developed. Grade 4 decreased neutrophils (15%) 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.

BRUIN evaluated Jaypirca in adult patients with R/R MCL who progressed on or were intolerant to a prior BTKi1,4||||

||||Ibrutinib (67%), acalabrutinib (30%), and zanubrutinib (8%) in the efficacy population.1
##Trial excluded patients with significant cardiovascular disease, major bleeding, or grade ≥3 arrhythmia with prior BTKi, prolonged QTc interval, or need for strong CYP3A inhibitor or inducer or strong P-gp inhibitor.1
***Not all patients in the safety population met criteria to be evaluated for efficacy.
†††Patients with active CNS lymphoma or allogeneic HSCT or CAR T-cell therapy within 60 days were excluded.1
‡‡‡The phase 1 primary outcome was to determine maximum tolerated dose and recommended phase 2 dose. All patients received at least one dose of Jaypirca.4

BTKi=BTK inhibitor; CAR=chimeric antigen receptor; CNS=central nervous system; ECOG=Eastern Cooperative Oncology Group; HSCT=hematopoietic stem cell transplantation; ULN=upper limit of normal.

MCL Patient Characteristics arrowRight Arrow Right

Explore the safety data

MCL safety

References:

  1. Jaypirca. Prescribing Information. Lilly USA, LLC.
  2. Data on File, Lilly USA, LLC, DOF-PT-US-0031.
  3. Data on File, Lilly USA, LLC, DOF-PT-US-0030.
  4. Mato AR, Shah NN, Jurczak W, et al. Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): a phase 1/2 study. Lancet. 2021;397(10277):892-901.
  5. Data on File, Lilly USA, LLC, DOF-PT-US-0033.
  6. Mato AR, Shah NN, Jurczak W, et al. Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): a phase 1/2 study. Lancet. 2021;397(10277)(suppl app):119-125.

Important Safety Information

Infections: Fatal and serious infections (including bacterial, viral, fungal) and opportunistic infections occurred in Jaypirca-treated patients. Across clinical trials, Grade ≥3 infections occurred (25%), most commonly pneumonia (20%); fatal infections (5%), sepsis (6%), and febrile neutropenia (3.8%) 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 for signs and symptoms, evaluate, and treat. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Hemorrhage: Fatal and serious hemorrhage has occurred with Jaypirca. Across clinical trials, major hemorrhage (Grade ≥3 bleeding or any central nervous system bleeding) occurred (2.6%), including gastrointestinal hemorrhage; fatal hemorrhage occurred (0.3%). Bleeding of any grade, excluding bruising and petechiae, occurred (16%). Major hemorrhage occurred when taking Jaypirca with (2.0%) and without (0.6%) antithrombotic agents. Consider risks/benefits of co-administering antithrombotic agents with Jaypirca. Monitor for signs of bleeding. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca. Consider withholding Jaypirca 3-7 days pre- and post-surgery based on surgery type and bleeding risk.

Cytopenias: Jaypirca can cause cytopenias, including neutropenia, thrombocytopenia, and anemia. Across clinical trials, Grade 3 or 4 cytopenias, including decreased neutrophils (27%), decreased platelets (13%), and decreased hemoglobin (11%), developed. Grade 4 decreased neutrophils (15%) and Grade 4 decreased platelets (6%) developed. Monitor complete blood counts regularly. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Cardiac Arrhythmias: Cardiac arrhythmias occurred in patients taking Jaypirca. Across clinical trials, atrial fibrillation or flutter were reported in 3.4% of Jaypirca-treated patients, with Grade 3 or 4 atrial fibrillation or flutter in 1.6%. Other serious cardiac arrhythmias such as supraventricular tachycardia and cardiac arrest occurred (0.4%). Cardiac risk factors such as hypertension or previous arrhythmias may increase risk. Monitor and manage signs and symptoms of arrhythmias (e.g., palpitations, dizziness, syncope, dyspnea). Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Second Primary Malignancies: Across clinical trials, second primary malignancies, including non-skin carcinomas, developed in 9% of Jaypirca-treated patients, most frequently non-melanoma skin cancer (4.4%). 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. If DILI is confirmed, discontinue Jaypirca.

Embryo-Fetal Toxicity: Jaypirca can cause fetal harm. 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 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 (≥30%) ARs in the pooled safety population of patients with hematologic malignancies (n=704) were decreased neutrophil count (54%), decreased hemoglobin (43%), decreased leukocytes (32%), fatigue (31%), decreased platelets (31%), decreased lymphocyte count (31%), calcium decreased (30%).

Mantle Cell Lymphoma

Serious ARs occurred in 38% of patients, with pneumonia (14%), COVID-19 (4.7%), musculoskeletal pain (3.9%), hemorrhage (2.3%), pleural effusion (2.3%), and sepsis (2.3%) occurring in ≥2% of patients. Fatal ARs within 28 days of last 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 Due to ARs: Dose reductions in 4.7%, treatment interruption in 32%, and permanent discontinuation of Jaypirca in 9% of patients. Permanent discontinuation in >1% of patients included pneumonia.

Most common ARs (≥15%) and Select Laboratory Abnormalities (≥10%) (all Grades %; Grade 3-4 %): hemoglobin decreased (42; 9), platelet count decreased (39; 14), neutrophil count decreased (36; 16), lymphocyte count decreased (32; 15), creatinine increased (30; 1.6), fatigue (29; 1.6), musculoskeletal pain (27; 3.9), calcium decreased (19; 1.6), diarrhea (19; -), edema (18; 0.8), dyspnea (17; 2.3), AST increased (17; 1.6), pneumonia (16; 14), bruising (16; -), potassium decreased (13; 1.6), sodium decreased (13; -), lipase increased (12; 4.4), ALT increased (11; 1.6), potassium increased (11; 0.8), alkaline phosphatase increased (11; -). Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (10), platelets decreased (7), lymphocytes decreased (6).

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma from Single-Arm and Randomized Controlled Clinical Trials

Serious ARs occurred in 47-56% of patients across clinical trials. Serious ARs in ≥5% of patients in the single-arm trial were pneumonia (18%), COVID-19 (9%), sepsis (7%), febrile neutropenia (7%). Serious ARs in ≥3% of patients in the randomized controlled trial were pneumonia (21%), COVID-19 (5%), sepsis (3.4%). Fatal ARs within 28-30 days of last Jaypirca dose occurred in 8-11% of patients, most commonly due to infections (7- 10%), including sepsis (5%), COVID-19 (2.7-5%), and pneumonia (3.4%).

Dose Modifications and Discontinuations Due to ARs: Dose reductions in 3.6-10%, treatment interruption in 42-51%, and permanent discontinuation of Jaypirca in 9-17% of patients. Permanent discontinuation in >1% of patients included second primary malignancy, pneumonia, COVID-19, neutropenia, sepsis, anemia, and cardiac arrhythmias.

Most common ARs and Select Laboratory Abnormalities (≥20%) (all Grades %, Grade 3-4 %)--in a randomized controlled trial: neutrophil count decreased (54; 26), hemoglobin decreased (45; 10), platelet count decreased (37; 17), pneumonia (28; 16), ALT increased (25; 1.8), creatinine increased (25; -), calcium decreased (23; 0.9), sodium decreased (22; 0.9), bilirubin increased (21; 0.9), upper respiratory tract infections (21; 0.9); in a single-arm trial: neutrophil count decreased (63; 45), hemoglobin decreased (48; 19), calcium decreased (40; 2.8), fatigue (36; 2.7), bruising (36; -), cough (33; -), musculoskeletal pain (32; 0.9), platelet count decreased (30; 15), sodium decreased (30; -), COVID-19 (28; 7), pneumonia (27; 16), diarrhea (26; -), abdominal pain (25; 2.7), lymphocyte count decreased (23; 8), ALT increased (23; 2.8), AST increased (23; 1.9), creatinine increased (23; -), dyspnea (22; 2.7), hemorrhage (22; 2.7), lipase increased (21; 7), alkaline phosphatase increased (21; -), edema (21; -), nausea (21; -), pyrexia (20; 2.7), headache (20; 0.9). Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (23).

Drug Interactions

Strong CYP3A Inhibitors: Concomitant use increased pirtobrutinib systemic exposure, which may increase risk of Jaypirca ARs. Avoid using strong CYP3A inhibitors with Jaypirca. If concomitant use is unavoidable, reduce Jaypirca dose according to approved labeling.

Strong or Moderate CYP3A Inducers: Concomitant use decreased pirtobrutinib systemic exposure, which may reduce Jaypirca efficacy. Avoid using Jaypirca with strong or moderate CYP3A inducers. If concomitant use with moderate CYP3A inducers is unavoidable, increase Jaypirca dose according to approved labeling.

Sensitive CYP2C8, CYP2C19, CYP3A, P-gp, or BCRP Substrates: Use with Jaypirca increased their plasma concentrations, which may increase risk of ARs related to these substrates for drugs sensitive to minimal concentration changes. Follow recommendations for these sensitive substrates in their approved labeling.

Use in Specific 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. Presence of pirtobrutinib in human milk is unknown. Advise women to use effective contraception and to not 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: Because severe renal impairment increases pirtobrutinib exposure, reduce Jaypirca dose in these patients according to approved labeling.

PT HCP ISI MCL_CLL Q42025

Please see full Prescribing Information and Patient Information for Jaypirca.

Indications

Jaypirca is indicated for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have previously been treated with a covalent BTK inhibitor.

Jaypirca is also indicated for the treatment of adult patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical trial benefit in a confirmatory trial.