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Jaypirca ® (pirtobrutinib) tablets
50 mg,100 mg
This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.
What adverse events lead to treatment discontinuation with Jaypirca® (pirtobrutinib)?
In the CLL-321 study, adverse events led to fewer drug discontinuations in the pirtobrutinib arm (17.2%) vs IdelaR/BR arm (34.9%). In the BRUIN study, 20 patients (2.6%) discontinued study treatment due to a treatment-related adverse event.
Label Recommendations
Recommended Dose Modifications of Pirtobrutinib for Adverse Reactions Based on a Starting Dosage of 200 mg describes the recommended dose modifications for adverse reactions to pirtobrutinib.
If any of the following adverse reactions... |
Occur for the... |
Then... |
And... |
|
first time |
interrupt pirtobrutinib until recovery to grade 1 or baseline |
restart at original dose level (200 mg daily)b. |
second time |
restart at 100 mg daily. |
||
third time |
restart at 50 mg daily. |
||
fourth time |
discontinue pirtobrutinib |
do not restart. |
aDose modification is not recommended for asymptomatic lymphocytosis. Asymptomatic lipase increase may not necessarily warrant dose modification.
bEvaluate the benefit-risk before resuming treatment at the same dose for a grade 4 non-hematological toxicity.
Treatment Discontinuation During Clinical Studies
Study CLL-321 and BRUIN have evaluated the use of pirtobrutinib for the treatment of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
- Study CLL-321 is a global, randomized, open-label, multicenter phase 3 trial comparing the safety and efficacy of pirtobrutinib 200 mg daily as continuous monotherapy to investigator’s choice of 2 comparator regimens: either idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR) in patients CLL or SLL who have been treated with at least a covalent Bruton's tyrosine kinase (BTK) inhibitor (NCT04666038).2,3
- BRUIN is a global, multicenter phase 1/2 trial evaluating pirtobrutinib in patients with previously treated CLL, SLL, or non-Hodgkin's lymphoma (NHL) who have failed or are intolerant to standard of care (NCT03740529).4,5
Due to the differences in the patient populations between the 2 studies, comparisons between the data sets should be avoided.
Criteria for Discontinuation of Study Treatment
In the both the BRUIN phase 1/2 study and CLL-321 phase 3 study, patients were free to discontinue study treatment at any time. Patients were advised that they would be followed for survival after discontinuing treatment. Over the course of the studies, the investigator and/or the study sponsor were to remove a patient from treatment for any of the following reasons:
- progressive disease (PD)
- In BRUIN: PD by disease-defined criteria. Patients with documented PD who tolerated study therapy and, in the opinion of the investigator, were deriving clinical benefit from continuing study treatment, were allowed to continue treatment with documented approval from the sponsor
- In CLL-321: PD by Internation Workshop on chronic lymphocytic leukemia (iwCLL) 2018 criteria. Patients with documented PD who tolerated treatment, were deriving clinical benefit, and who were likely to experience a worse outcome with discontinuing therapy were allowed to continue with prior sponsor approval
- unacceptable toxicity
- intercurrent illness compromising ability to fulfill protocol requirements
- pregnancy
- requirement for alternative treatment in the opinion of the investigator, unless such treatment was temporary (eg, local radiation or surgery for disease that did not meet the definition of progressive disease)
- dose delays
- In BRUIN: dose delay >28 days, unless a clinical need for prolonged delay had been determined by the investigator with documented approval from the sponsor
- In CLL-321:
- Pirtobrutinib arm: dose delay > 28 days for hematologic toxicity, unless a clinical need for prolonged delay is determined by the investigator with documented sponsor approval
- Idela/BR arm: dose delay > 28 days for unacceptable toxicity, consult product package insert
- significant noncompliance with the study protocol
- withdrawal of consent by the patient
- loss to follow-up
- death
- study termination by the sponsor, or
- any medical condition that the investigator determined to be a clinically significant finding after enrollment, which may jeopardize the patient’s safety if study treatment is continued (CLL-321 study only).3,5
Adverse Events Leading to Treatment Discontinuations in the Phase 3 CLL-321 Study
As of the data cutoff date of August 29, 2024, CLL-321 randomized 238 patients, with 119 receiving pirtobrutinib and 119 receiving IdelaR/BR (IdelaR, n=82 [68.9%]; BR n=37 [31.1%]). A safety analysis was conducted in the patients that received treatment, including 116 patients in the pirtobrutinib treatment group and 109 patients in the IdelaR/BR treatment group.3
Of the 116 patients who received pirtobrutinib, 20 patients (17.2%) discontinued study treatment due to an adverse event (AE) compared with 38 patients (34.9%) who received treatment with IdelaR or BR (Adverse Events Leading to Treatment Discontinuation in >1% Patients in the CLL-321 Phase 3 Study).3
AE |
Pirtobrutiniba |
IdelaR or BRb |
||
TEAE |
TRAE |
TEAE |
TRAE |
|
AE leading to discontinuation of study treatment |
20 (17.2) |
6 (5.2) |
38 (34.9) |
23 (21.1) |
Infections and infestations |
11 (9.5) |
0 |
10 (9.2) |
2 (1.8) |
COVID-19 pneumonia |
3 (2.6) |
0 |
1 (0.9) |
1 (0.9) |
Pneumonia |
3 (2.6) |
0 |
3 (2.8) |
1 (0.9) |
COVID-19 |
2 (1.7) |
0 |
2 (1.8) |
0 |
Anemia |
2 (1.7) |
1 (0.9) |
0 |
0 |
Neutropenia |
2 (1.7) |
1 (0.9) |
0 |
0 |
Cardiac disorders |
2 (1.7) |
2 (1.7) |
1 (0.9) |
0 |
GI disorders |
1 (0.9) |
1 (0.9) |
9 (8.3) |
8 (7.3) |
Skin and subcutaneous tissue disorders |
1 (0.9) |
1 (0.9) |
5 (4.6) |
5 (4.6) |
Vascular disorders |
1 (0.9) |
0 |
2 (1.8) |
0 |
Metabolism and nutrition disorders |
0 |
0 |
4 (3.7) |
2 (1.8) |
Pyrexia |
0 |
0 |
2 (1.8) |
1 (0.9) |
ALT increased |
0 |
0 |
5 (4.6) |
5 (4.6) |
Abbreviations: AE = adverse event; ALT = alanine aminotransferase; BR = bendamustine + rituximab; CTCAE = Common Terminology Criteria for Adverse Events; COVID = coronavirus disease; GI = gastrointestinal; IdelaR = idelalisib + rituximab; MedDRA = Medical Dictionary of Regulatory Activities; NA = not available; TEAE = treatment-emergent adverse event; TRAE = treatment-related adverse event.
aAll randomized patients who received at least 1 dose of pirtobrutinib.
bAll randomized patients who received at least 1 dose of either IdelaR or BR.
Adverse Events Leading to Treatment Discontinuations in the BRUIN Study
Adverse Events Leading to Treatment Discontinuation Among Patients With MCL
As of the data cutoff date of January 31, 2022, the BRUIN trial enrolled 725 patients for treatment with pirtobrutinib monotherapy. Of 725 patients, 164 were patients with mantle cell lymphoma (MCL).6 The study assessed safety in 128 patients with MCL who had received pirtobrutinib 200 mg monotherapy and a prior BTK inhibitor.1
Of the 128 patients with MCL included in the safety population, 12 patients (9.4%) discontinued study treatment due to an AE (Adverse Events Leading to Treatment Discontinuation in >1% Patients With MCL in the BRUIN Phase 1/2 Study).1,7
MCL Patientsc, n (%) |
|
Any AE leading to discontinuation of study treatment, n (%) |
12 (9.4) |
Pneumonia |
2 (1.6) |
Abbreviations: AE = adverse event; BTK = Bruton's tyrosine kinase; MCL = mantle cell lymphoma; MedDRA = Medical Dictionary for Regulatory Activities.
aThe reported AE terms were coded using MedDRA version 24.0.
bAt each level of patient summarization, a patient was counted only once if the patient reported one or more events.
cPatients with MCL who received a prior BTK inhibitor with 200 mg once daily pirtobrutinib as starting dose and without subsequent dose escalation.
Adverse Events Leading to Treatment Discontinuation Among Patients With CLL/SLL
As of the data cut-off date on February 8, 2023, 778 patients had been enrolled in the BRUIN trial for treatment with pirtobrutinib monotherapy, of which 317 were patients CLL or SLL.7 Among these patients with CLL/SLL, an analysis was conducted in the subset of patients who received a starting dose of pirtobrutinib 200 mg monotherapy once daily and treatment with ≥2 prior lines of therapy, including a BTK inhibitor and B-cell lymphoma-2 (BCL-2) inhibitor.1,7
Of the 110 patients with CLL/SLL included in the safety population, 10 patients (9.1%) discontinued study treatment due to an AE (Adverse Events Leading to Treatment Discontinuation in >1% Patients With CLL/SLL in the BRUIN Phase 1/2 Study).1,7
CLL/SLL Patientsc, n (%) |
|
Any AE leading to discontinuation of study treatment, n (%) |
10 (9.1) |
COVID-19 |
2 (1.8) |
Sepsis |
2 (1.8) |
Second primary malignancy |
3 (2.7) |
Abbreviations: AE = adverse event; BCL-2 = B-cell lymphoma-2; BTK = Bruton's tyrosine kinase; CLL = chronic lymphocytic leukemia; MedDRA = Medical Dictionary for Regulatory Activities; SLL = small lymphocytic lymphoma.
aDenotes a preferred term grouping, which includes multiple related terms. Adverse events categorized using MedDRA 24.0.
bAt each level of patient summarization, a patient was counted only once if the patient reported one or more events.
cPatients with CLL/SLL who received 200 mg once daily pirtobrutinib as starting dose and prior treatment with a BTK inhibitor and BCL-2 inhibitor.
Adverse Events Leading to Treatment Discontinuation Among All Patients in the BRUIN Study
As of the data cutoff date of July 29, 2022, the BRUIN trial enrolled 773 patients for treatment with pirtobrutinib monotherapy. A safety analysis was conducted for the overall pirtobrutinib monotherapy dataset which was defined as all enrolled MCL, CLL/SLL, and NHL patients from phase 1 and phase 2 of the BRUIN study who received ≥1 dose of pirtobrutinib.7,8
Of the 773 patients included in the overall safety population, 20 patients (2.6%) discontinued study treatment due to a treatment-related AE.9
Discontinuation of study treatment due to treatment-emergent AEs in all patients in the BRUIN trial is summarized in Treatment-Emergent Adverse Events Leading to Treatment Discontinuation in All Patients in the BRUIN Phase 1/2 Study. Adverse Events of Special Interest Leading to Treatment Discontinuation in All Patients in the BRUIN Phase 1/2 Study summarizes the rates of discontinuation in patients who reported AEs of special interest which were defined as AEs previously associated with covalent BTK inhibitors.
TEAE Occurring in ≥15% Patients |
All Patientsa, (%) |
Neutropeniab |
0.5 |
COVID-19 |
0.4 |
Fatigue |
0.3 |
Nausea |
0.1 |
Dyspnea |
0.1 |
Abdominal pain |
0.1 |
Abbreviations: CLL = chronic lymphocytic leukemia; COVID-19 = coronavirus disease-2019; MCL = mantle cell lymphoma; SLL = small lymphocytic lymphoma; NHL= non-Hodgkin's lymphoma; TEAE = treatment-emergent adverse event.
aAll enrolled MCL, CLL/SLL, and NHL patients from phase 1 and phase 2 of the BRUIN study who received ≥1 dose of pirtobrutinib.
bAggregate of neutropenia and neutrophil count decreased.
Adverse Event of Special Interesta |
All Patientsb, (%) |
Rashc |
0.1 |
Abbreviations: BTK = Bruton's tyrosine kinase; CLL = chronic lymphocytic leukemia; MCL = mantle cell lymphoma; SLL = small lymphocytic lymphoma; NHL= non-Hodgkin's lymphoma.
aAdverse events that were previously associated with covalent BTK inhibitors.
bAll enrolled MCL, CLL/SLL, and NHL patients from phase 1 and phase 2 of the BRUIN study who received ≥1 dose of pirtobrutinib.
cAggregate of preferred terms including rash.
Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Jaypirca [package insert]. Indianapolis, IN: Eli Lilly and Company; 2024.
2Study of LOXO-305 versus investigator's choice (IdelaR or BR) in patients with previously treated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) (BRUIN CLL-321). Clinicaltrials.gov identifier: NCT04666038. Updated April 20, 2025. Accessed May 12, 2025. https://clinicaltrials.gov/ct2/show/NCT04666038
3Sharman JP, Munir T, Grosicki S, et al. Phase III trial of pirtobrutinib vs. idelalisib/rituximab or bendamustine/rituximab in cBTKi pretreated chronic lymphocytic leukemia/small lymphocytic lymphoma (BRUIN CLL-321). J Clin Oncol. Published online June 6, 2025. https://doi.org/10.1200/JCO-25-00166
4A study of oral LOXO-305 in patients with previously treated CLL/SLL or NHL. ClinicalTrials.gov identifier: NCT03740529. Updated April 6, 2025. Accessed May 12, 2025. https://www.clinicaltrials.gov/ct2/show/NCT03740529
5Mato 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. https://doi.org/10.1016/S0140-6736(21)00224-5
6Wang ML, Shah NN, Jurczak W, et al. Efficacy of pirtobrutinib in covalent BTK-inhibitor pre-treated relapsed/refractory mantle cell lymphoma: additional patients and extended follow-up from the phase 1/2 BRUIN study. Poster presented at: 64th Annual Meeting of the American Society of Hematology (ASH); December 10-13, 2022; New Orleans, Louisiana. Accessed December 10, 2022.
7Data on file, Eli Lilly and Company and/or one of its subsidiaries.
8Mato AR, Woyach JA, Brown JR, et al. Efficacy of pirtobrutinib in covalent BTK-inhibitor pre-treated relapsed/refractory CLL/SLL: additional patients and extended follow-up from the phase 1/2 BRUIN study. Abstract presented at: 64th Annual Meeting of the American Society of Hematology (ASH); December 10-13, 2022; New Orleans, Louisiana. Accessed December 10, 2022. https://doi.org/10.1182/blood-2022-159497
9Roeker LE, Coombs CC, Shah NN, et al. Safety of extended pirtobrutinib exposure in relapsed and/or refractory B-cell malignancies. Acta Hematologica. 2025;148(2):180-197. https://doi.org/10.1159/000539587
10Coombs CC, Shah NN, Jurczak W, et al. Long-term safety with ≥12 months of pirtobrutinib in relapsed/refractory (R/R) B-cell malignancies. Poster presented at: 59th Annual Meeting of the American Society of Clinical Oncology (ASCO); June 2-8, 2023; Chicago, Illinois. Accessed June 2, 2023.
Date of Last Review: February 20, 2025