Common ARs were mostly Grade 1/2¹

Adverse reactions reported (≥10%) in patients with R/R MCL previously treated with a BTKi¹

Nonhematologic ARs chart in patients with R/R MCL

^aEach term listed includes other related terms.¹
^bIncludes 1 fatality from COVID-19 pneumonia.¹
^cIncludes 1 fatality from hemorrhage.¹

The following adverse reaction results (≥10%) were reported in patients with previously treated R/R MCL who received Jaypirca 200 mg once daily (N=128). The all-grades adverse reactions reported were general disorders: fatigue (29%), edema (18%), and fever (13%); musculoskeletal and connective tissue disorders: musculoskeletal pain (27%) and arthritis/arthralgia (12%); gastrointestinal disorders: diarrhea (19%), constipation (13%), abdominal pain (11%) and nausea (11%); respiratory, thoracic, and mediastinal disorders: dyspnea (17%) and cough (14%); injury: bruising (16%); infections: pneumonia (16%) and upper respiratory tract infections (10%); nervous system disorders: peripheral neuropathy (14%) and dizziness (10%); skin and subcutaneous disorders: rash (14%); and vascular disorders: hemorrhage (11%).¹

The Grade 3 or 4 adverse reactions reported for patients with MCL who received Jaypirca were fatigue (1.6%), edema (0.8%), musculoskeletal pain (3.9%), arthritis/arthralgia (0.8%), abdominal pain (0.8%), dyspnea (2.3%), pneumonia (14%), upper respiratory tract infections (0.8%), peripheral neuropathy (0.8%), and hemorrhage (3.1%).¹

Fatigue, edema, fever, musculoskeletal pain, arthritis/arthralgia, diarrhea, constipation, abdominal pain, nausea, dyspnea, cough, bruising, pneumonia, upper respiratory tract infections, peripheral neuropathy, dizziness, rash, and hemorrhage included other related terms.¹

The incidence of all-grade pneumonia includes one fatality from COVID-19 pneumonia.¹

The incidence of all-grade hemorrhage includes one fatality from hemorrhage.¹

Of 128 patients with MCL, 36% were exposed to Jaypirca for 6 months or longer and 10% were exposed for ≥1 year.¹

Serious adverse reactions occurred in 38% of patients who received Jaypirca. Serious adverse reactions that occurred 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%).¹

SELECT IMPORTANT SAFETY INFORMATION

Fatal Adverse Reactions (ARs): Fatal ARs within 28 days of the last Jaypirca dose occurred in 7% of patients with MCL, most commonly due to infections (4.7%), including COVID-19 (3.1% of all patients).

Atrial fibrillation or flutter occurred in less than 5% of patients with R/R MCL²

Atrial fibrillation or atrial flutter with Jaypirca 200 mg once daily in patients with R/R MCL previously treated with a BTKi (n=128)^2*

Atrial fibrillation or atrial flutter with Jaypirca in MCL — In patients with R/R MCL previously treated with a BTKi (n=128) who received Jaypirca 200 mg once daily, all grade atrial fibrillation or atrial flutter occurred in 3.9% of patients; grade 3 or 4 atrial fibrillation or flutter occurred in 1.6% of patients.²

*ECG was routinely performed at regular intervals throughout the trial.³

In 128 patients with MCL:

At the time of initial analysis, 36% were exposed to Jaypirca for ≥6 months and 10% were exposed for ≥1 year^1,2
Clinically relevant ARs in <10% include vision changes, memory changes, headache, urinary tract infection, herpesvirus infection, and tumor lysis syndrome¹

SELECT IMPORTANT SAFETY INFORMATION

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%). Patients with cardiac risk factors may be at increased risk. Monitor and manage signs and symptoms of arrhythmias and reduce dose, temporarily withhold, or permanently discontinue Jaypirca, based on severity.

In patients with R/R MCL previously treated with a BTKi

Select laboratory abnormalities^† (≥10%) that worsened from baseline¹

Lab abnormalities chart in patients with R/R MCL

^†The denominator used to calculate the rate varied from 90 to 127 based on the number of patients with a baseline value and at least one post-treatment value.¹

The following laboratory abnormality results were reported for patients who received Jaypirca 200 mg once daily. The all-grades laboratory abnormalities reported for patients were hemoglobin decreased (42 percent), platelet count decreased (39 percent), neutrophil count decreased (36 percent), lymphocyte count decreased (32 percent), creatinine increased (30 percent), calcium decreased (19 percent), AST increased (17 percent), potassium decreased (13 percent), sodium decreased (13 percent), lipase increased (12 percent), alkaline phosphatase increased (11 percent), ALT increased (11 percent), potassium increased (11 percent).¹

The Grades 3 or 4 laboratory abnormalities reported for patients were hemoglobin decreased (9 percent), platelet count decreased (14 percent), neutrophil count decreased (16 percent), lymphocyte count decreased (15 percent), creatinine increased (1.6 percent), calcium decreased (1.6 percent), AST increased (1.6 percent), potassium decreased (1.6 percent), lipase increased (4.4 percent), ALT increased (1.6 percent), potassium increased (0.8 percent).¹

Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (10%), platelets decreased (7%), and lymphocytes decreased (6%).¹

Upon initiation of Jaypirca, a temporary increase in lymphocyte counts (defined as absolute lymphocyte count increased ≥50% from baseline and a post-baseline value ≥5,000/μL) occurred in 34% of patients with MCL in BRUIN. The median time to onset of lymphocytosis was 1.1 weeks, with 75% of cases occurring within 2.1 weeks, and the median duration was 11 weeks.¹

ALT=alanine aminotransferase; AR=adverse reaction; AST=aspartate aminotransferase; BTKi=Bruton’s tyrosine kinase inhibitor; ECG=electrocardiogram; MCL=mantle cell lymphoma; R/R=relapsed or refractory.

Treatment discontinuations and dose modifications¹

Few patients permanently discontinued due to adverse reactions¹

Discontinuation Rate Due to ARs in Patients with MCL¹

Discontinuation rates in patients with R/R MCL — 9 percent of patients with MCL (n equals 12 out of 128) permanently discontinued treatment due to adverse reactions

Due to treatment-emergent ARs in the 128 patients with MCL,

4.7% (6/128 patients) required dose reductions^1‡
32% (41/128 patients) experienced treatment interruption¹

Adverse reactions that resulted in dosage modification in >5% of patients included pneumonia and neutropenia. Adverse reactions which resulted in permanent discontinuation of Jaypirca in >1% of patients included pneumonia.¹

^‡See the full Prescribing Information for information about dose modifications due to adverse reactions.¹

Featured Peer Insights

Sparking Discussions about Jaypirca: Safety Data for Jaypirca

Join Dr. Julio Chavez as he reviews the safety data for Jaypirca.

0:00–0:01
[Music with a medium beat begins, logo, and Indication animate into view. Music continues for the rest of the video]

0:02–0:05
[Thought Leader introduces the video series while main title screen animates into view]
Welcome to this episode of the Sparking Discussions about Jaypirca video series.

0:06–0:11
[The titles of each episode in the video series animates in, and pill graphic settles on title of this video]

0:12–0:14
[A montage of behind-the-scenes footage with the Thought leader getting ready to film this video is seen]

0:15–0:16
[Thought Leader seen in chair while credentials animate onscreen]
I am Dr Julio Chavez,

0:17–0:26
[Thought Leader begins to summarize what this video is about as credentials fade out and text animates onscreen]
…and today I’ll be walking you through the safety data for Jaypirca, the first-and-only approved reversible, or noncovalent, BTK inhibitor.

0:28–0:43
[Voice over providing the Indication statement begins]
Jaypirca is a kinase inhibitor indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma after at least two lines of systemic therapy, including a BTK inhibitor.

0:43–1:17
[Voice over providing safety introduction]
Please refer to the Important Safety Information and the full Prescribing Information regarding warnings and precautions about the use of Jaypirca, like infections, hemorrhage, cytopenias, atrial fibrillation and atrial flutter, second primary malignancies, hepatotoxicity, including drug-induced liver injury, and embryo-fetal toxicity. A summary of important safety information for Jaypirca will be covered later in this video.

1:17–1:31
[Thought Leader concludes summarizing the video while text animates onscreen]
Some of the main topics we will be getting into are:

Common adverse reactions
Discontinuation rate due to adverse reactions
Other adverse events of clinical interest

1:32–1:36
[Scene transitions to Thought Leader speaking through camera monitor]
As you may know, patients who have relapsed or refractory disease…

1:37–1:47
[Scene shifts back to Thought Leader sitting as speaks about patients]
…may have had multiple lines of therapy and may have had to discontinue one or more along the way because of disease progression or tolerability issues.

1:47–1:53
[Thought Leader is now seen from a side angle as he continues discussing patients]
This ultimately limits the number of options they have over time.

1:54–2:13
[BRUIN trial information begins to animate onscreen as Thought Leader asks questions]
You might ask, “Can patients tolerate Jaypirca if they’ve been exposed to a number of prior agents?” Or “Will tolerability be compromised if this drug is clinically effective?” These are fair questions. And we hope during this video to help you judge for yourself.

2:14–2:19
[Thought Leader begins to introduce the BRUIN trial]
So let’s look first at the design of the BRUIN study and the patients who were included.

2:20-3:11
[Thought Leader starts discussing the BRUIN study as study graphic appears onscreen]
BRUIN was a phase 1/2, open-label, single-arm trial that evaluated Jaypirca in adults with hematologic malignancies. Patients received Jaypirca 200 milligrams once daily until disease progression or unacceptable toxicity. Patients had received a median of 3 prior lines of therapy. The safety population included 128 patients with relapsed or refractory MCL who were previously treated with a BTK inhibitor. The trial excluded patients with active CNS involvement by lymphoma, significant cardiovascular disease, major bleeding or grade 3 or greater arrhythmia with a prior BTK inhibitor, prolonged QTc interval, or need for a strong CYP3A inhibitor or inducer or strong P-gp inhibitor.

3:12-3:17
[Graphic swipes away as adverse reactions graphic begins to appear onscreen]
Now let’s take a look at the numbers for patients with MCL in BRUIN.

3:18-4:00
[Adverse reactions graphic swipes onscreen as Thought Leader discusses the data]
The first thing to note is that most common adverse reactions were mostly grade 1 or 2.
As you’ll notice, the most common were fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, and bruising. A few categories had grade 3 or 4 adverse reactions, including pneumonia in 14% of patients, musculoskeletal pain in about 4%, and hemorrhage in 3.1%—all definitely safety signals to be aware of. In addition, serious adverse reactions occurred in 38% of patients who received Jaypirca.

4:00-4:35
[Adverse reaction graphic is replaced by Discontinuation Rate graphics while Thought Leader is seen onscreen]
Another aspect of the trial that stood out was the discontinuations. In this previously treated population, few patients with MCL permanently discontinued Jaypirca during the trial due to adverse reactions. Out of the 128 patients with MCL, 9% permanently discontinued treatment. In addition, dose reductions occurred in just under 5% of these patients, and treatment interruptions occurred in 32%.

4:36-4:50
[Medium shot of Thought Leader with laboratory abnormality graphic onscreen]
There were some grade 3 or grade 4 laboratory findings that were reported for patients in the BRUIN trial, including anemia, thrombocytopenia, neutropenia, and lymphopenia.

4:51-4:53
[Thought Leader swipes off screen while laboratory abnormality graphic remains onscreen]

4:54-5:53
[Adverse event graphic swipes in as Thought Leader summarizes the data]
Please consider that the adverse events shown here were of clinical interest based on the known safety profile of BTK inhibitor therapies, preclinical toxicology, and emerging safety data during this study. For adverse events of all grades occurring in less than 10% of patients, peripheral edema was observed in 9% of patients, vision changes in 7%, and memory changes in 7%. Of particular clinical interest, atrial fibrillation or atrial flutter across all grades was observed in around 4% of patients.

Also, monitor patients with cardiac risk factors, such as hypertension or previous arrhythmias, as they may be at increased risk for atrial fibrillation and atrial flutter when treated with Jaypirca.

Overall, I found these results encouraging for those patients with relapsed or refractory MCL.

5:54–6:04
[Thought Leader expresses some of his conclusions based on the safety data as a quote animates in]
Based on the safety and tolerability data from the BRUIN trial, the study results reassure me that Jaypirca is a viable clinical option I would consider.

6:05-6:15
[Medium shot of Thought Leader as he provides a recommendation on safety during treatment]
Nevertheless, I’m sure you recognize that it’s always important to monitor for side effects such as atrial fibrillation and cytopenias during treatment.

6:16-6:30
[Close-up of Thought Leader as a quote animates onscreen]
What I’ve shared with you here is not just my point of view as a fellow clinician, but is based on safety results assessed across more than 100 patients with MCL treated with Jaypirca in the phase 1/2 BRUIN study.

6:31-7:03
[Medium shot of Thought Leader sharing closing thoughts as the title of the series animates onscreen]
I want to thank you for reviewing the safety data with me in this presentation—and I invite you to view the other videos and share the entire series with your peers to learn more about Jaypirca.

The safety data we’ve reviewed is specific to the MCL population in the BRUIN study.
As noted earlier, additional safety information from the overall BRUIN population of patients with hematologic malignancies follows.

7:04-7:05
[Final safety message animates into view]

7:06-12:37
[Voice over of the Indication and Accelerated Approval statement, along with the Select Important
Safety Summary for Jaypirca is heard as the safety content scrolls onscreen]

Indication
Jaypirca is a kinase inhibitor indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma, or 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 benefit in a confirmatory trial.

Select Important Safety Summary for Jaypirca (pirtobrutinib)
Fatal and serious infections (including bacterial, viral, or fungal) and opportunistic infections have occurred in patients treated with Jaypirca. Consider prophylaxis, including vaccinations, in patients at increased risk. Monitor for signs and symptoms of infection, evaluate promptly, and treat appropriately.

Fatal and serious hemorrhage has occurred in Jaypirca-treated patients. Major hemorrhage, including gastrointestinal hemorrhage, occurred. Monitor patients for bleeding and treat appropriately. Consider withholding Jaypirca 3-7 days pre- and post-surgery depending on bleeding risk.

Jaypirca can cause cytopenias, including neutropenia, thrombocytopenia, and anemia. Grade 3 or 4 cytopenias, including decreased neutrophils, decreased platelets, and decreased hemoglobin, and Grade 4 decreased neutrophils and Grade 4 decreased platelets developed. Monitor complete blood counts during treatment.

Cardiac arrhythmias occurred in Jaypirca-treated patients, including Grade 3 or 4 atrial fibrillation or flutter. Serious cardiac arrhythmias, such as supraventricular tachycardia and cardiac arrest occurred. Patients with cardiac risk factors may be at increased risk. Monitor for signs and symptoms of arrhythmias and manage appropriately.

Second primary malignancies, including skin cancers and non-skin carcinomas, have developed in Jaypirca-treated patients. Monitor, and advise patients to use sun protection.

Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of drug-induced liver injury (DILI), has occurred with BTK inhibitors, including Jaypirca. Evaluate bilirubin and transaminases at baseline and throughout treatment. Patients who develop abnormal liver tests after Jaypirca require more frequent monitoring. If DILI is suspected, withhold Jaypirca; if confirmed, discontinue Jaypirca.

Jaypirca can cause fetal harm. Advise females of reproductive potential of fetal risk and to use effective contraception. Advise women not to breastfeed.

Serious adverse reactions occurred in 38% and fatal adverse reactions occurred in 7% of patients with MCL. The most common adverse reactions (≥15%), excluding laboratory terms, were fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, and bruising. Grade 4 laboratory abnormalities in >5% of patients were decreased neutrophils, platelets, and lymphocytes.

Adverse reactions led to dose reductions in 4.7%, treatment interruption in 32%, and permanent discontinuation of Jaypirca in 9% of patients. Adverse reactions resulting in permanent discontinuation in >1% of patients included pneumonia.

Concomitant use of Jaypirca with sensitive CYP2C8, CYP2C19, CYP3A, P-gp, or BCRP substrates may increase risk of adverse reactions related to these substrates for drugs sensitive to minimal concentration changes. Follow recommendations for these sensitive substrates in their approved labeling.

Avoid concomitant use of Jaypirca with strong CYP3A inhibitors and with strong or moderate CYP3A inducers. If concomitant use with strong CYP3A inhibitors or with moderate CYP3A inducers is unavoidable, modify Jaypirca dosage according to the approved labeling.

Patients aged 65 years and older experienced higher rates of Grade 3 and higher adverse reactions and serious adverse reactions compared to patients younger than age 65 years.

Because severe renal impairment increases pirtobrutinib exposure, reduce Jaypirca dosage in these patients, according to approved labeling.

This is not the complete safety information for Jaypirca. Please see full Important Safety Information and links to the Prescribing Information and Patient Information on the surrounding web page.

12:38-12:44
[Scene transition to the sign-off screen with a message to continue the video series, logos, references, and legal language]

Watch other videos

Is Jaypirca the right option for your patients?

Discover Patient Characteristics

References:

Jaypirca. Prescribing Information. Lilly USA, LLC.
Data on File, Lilly USA, LLC, DOF-PT-US-0006.
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.):1-158.

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.

MCL Safety

Common ARs were mostly Grade 1/21

Of 128 patients with MCL, 36% were exposed to Jaypirca for 6 months or longer and 10% were exposed for ≥1 year.1

Atrial fibrillation or flutter occurred in less than 5% of patients with R/R MCL2