CurrentmhnPolicy CP.PHAR.620

Pirtobrutinib (Jaypirca) coverage policy

Defines medical necessity criteria, approval durations, dosing limits, and allowed indications (FDA and NCCN-supported off-label) for pirtobrutinib (Jaypirca) across Commercial, HIM/ICHRA, and Medicaid lines of business.

Policy Summary

Payermhn

PolicyPirtobrutinib (Jaypirca) coverage policy

Policy CodePolicy CP.PHAR.620

Change TypeMultiple substantive updates

Effective DateJun 1, 2023

Next Review Date

Key ActionProvider must submit documentation (office chart notes, lab results or other clinical information) supporting that member has met all approval criteria; prior authorization may be required for certain indications.

SourceLink

POLICY UPDATE CHANGES

Added ICHRA line of business and clarified prior therapy requirement with a covalent BTK inhibitor for MZL.

For CLL/SLL, updated FDA approval status and simplified prior therapy requirement to 'Member has received prior treatment with a covalent BTK inhibitor'; extended initial approval duration from 6 to 12 months.

Added maximum dose criteria when concomitant use with CYP3A inducers and updated dosing limits.

Added criteria for MZL and Waldenström macroglobulinemia per NCCN compendium.

3FDA-approved Indications Covered

2NCCN off-label Indications Covered

12Typical Approval Duration (months)

Coverage Summary

Coverage stance: covered_with_criteria. Scope: defines medical necessity criteria, approval durations, dosing limits, and allowed indications (FDA and NCCN-supported off-label) for pirtobrutinib (Jaypirca) across Commercial, HIM/ICHRA, and Medicaid lines of business.

FDA-approved indications: pirtobrutinib is indicated for adult patients with relapsed/refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy including a BTK inhibitor, and for relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) previously treated with a covalent BTK inhibitor (per prescribing information).

NCCN-supported off-label indications: policy incorporates NCCN compendium-supported uses (examples include marginal zone lymphoma and Waldenström macroglobulinemia as subsequent therapy).

Typical approval duration: 12 months for Medicaid/HIM/ICHRA and 12 months (or duration of request, whichever is less) for Commercial.

Dosing thresholds: standard dose limit is 200 mg per day; 2 tablets per day. With concomitant CYP3A inducers and prescriber attestation, allowance up to 300 mg per day; 3 tablets per day. Age threshold: ≥ 18 years. Minimum treatment prior to continuation: at least 30 days.

Key thresholds

Age≥ 18 years

Prior lines for MCL≥ 2 prior lines of therapy

Standard dose limit200 mg per day (2 tablets per day)

Dose limit with CYP3A inducer300 mg per day (3 tablets per day) with prescriber attestation of inability to avoid concomitant CYP3A inducer

Minimum treatment duration for continuationAt least 30 days of therapy prior to continuation

Initial Therapy Criteria

Continuation / Quantity Change Criteria

Other / Off-Label Indications

Provider Actions & Prior Authorization

Prior Authorization

Documentation required for approval

Provider must submit documentation (such as office chart notes, lab results, or other clinical information) supporting that the member has met all approval criteria. Prior authorization may be required.

Office notes, relevant progress notes, and oncology consults
Relevant laboratory results and pathology reports
Medication history and prior therapy documentation

Documentation Required

Prescriber attestation for CYP3A inducers

When requesting pirtobrutinib doses up to 300 mg/day, the prescriber must attest that the member cannot avoid concomitant use of a strong CYP3A inducer. Examples of CYP3A inducers include carbamazepine, rifampin, ritonavir, and St. John's wort.

Applicable Codes & Comparators

Product availability / NDC not listedNDC

No codes listed

Relevant comparator BTK inhibitors mentioned (informational)mixed

	Imbruvica (ibrutinib)
	Brukinsa (zanubrutinib)
	Calquence (acalabrutinib)

Clinical Evidence & Regulatory Support

BRUINKey trial: BRUIN phase 1/2 study (Lancet 2021) - pivotal evidence for pirtobrutinib in relapsed/refractory B‑cell malignancies

Lancet2021BRUIN phase 1/2 reported in Lancet (Mato et al.); subsequent BRUIN updates in Clin Lymphoma Myeloma Leuk and NEJM publications cited

FDARegulatory: CLL/SLL approval converted from accelerated to full approval per policy revision history; prescribing information cited

LabelPIRegulatory sources: Jaypirca prescribing information and NCCN compendia referenced for indications and dosing

Key evidence includes the BRUIN phase 1/2 study and subsequent publications (Lancet 2021; NEJM 2023 and other BRUIN updates) supporting activity of pirtobrutinib in relapsed/refractory B‑cell malignancies.

Regulatory support: Jaypirca prescribing information and NCCN compendia are cited as supporting documents; the policy notes that CLL/SLL approval was converted from accelerated to full approval per the revision history and updated prescribing information.

Dosing limits and rationale: pivotal and regulatory documents specify a standard maximum of 200 mg per day (2 tablets), with a defined allowance up to 300 mg per day (3 tablets) when the prescriber attests the member cannot avoid concomitant use of a CYP3A inducer (examples include carbamazepine, rifampin, ritonavir, St. John's wort).

Background

Pirtobrutinib (Jaypirca) is a noncovalent (reversible) Bruton tyrosine kinase (BTK) inhibitor.

Primary FDA indications include: relapsed/refractory mantle cell lymphoma (MCL) after ≥ 2 prior lines of systemic therapy including a BTK inhibitor, and relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in patients previously treated with a covalent BTK inhibitor (per prescribing information).

The policy includes NCCN compendium‑supported off‑label indications such as marginal zone lymphoma (MZL) and Waldenström macroglobulinemia/lymphoplasmacytic lymphoma as subsequent therapy, with specific prior therapy requirements (for MZL, prior treatment with a covalent BTK inhibitor).

Dosing limits are specified to support safety and drug interactions: standard dosing is 200 mg once daily (200 mg/day; 2 tablets), with an allowance up to 300 mg once daily (300 mg/day; 3 tablets) when prescriber attests inability to avoid concomitant CYP3A inducers; product availability is tablets of 50 mg and 100 mg.

Definitions

BTKBruton tyrosine kinase

CLLChronic lymphocytic leukemia

MCL

Revision History

03.31.26addedLatest

Added ICHRA line of business and clarified prior therapy requirement for MZL to specify prior treatment with a covalent BTK inhibitor (per 2Q 2026 annual review).

12.12.25revised

For CLL/SLL, FDA approval status updated from accelerated to full approval and prior therapy requirement simplified to 'Member has received prior treatment with a covalent BTK inhibitor'; initial approval duration extended from 6 to 12 months (RT4 changes 12.12.25).

02.12.24revised

Policy Summary

Payermhn

PolicyPirtobrutinib (Jaypirca) coverage policy

Policy CodePolicy CP.PHAR.620

Change TypeMultiple substantive updates

Effective DateJun 1, 2023

Next Review Date

SourceLink

On This Page

Attestation required for requests of doses up to 300 mg/day
Examples of CYP3A inducers: carbamazepine, rifampin, ritonavir, St. John's wort

Denial Risk

Non-covered indications

Requests for non–FDA approved indications that are not specifically addressed in this policy will be denied unless the prescriber provides sufficient documentation of efficacy and safety consistent with the applicable off‑label use policies.

Off‑label use policies: CP.CPA.09 (Commercial), HIM.PA.154 (Marketplace/ICHRA), CP.PMN.53 (Medicaid)
Sufficient documentation may include practice guidelines, NCCN recommendations, or peer‑reviewed literature supporting the requested use

Prior Authorization

Special handling for recent label changes

If the drug label has changed within the last 6 months and this policy has not yet been updated, follow the applicable formulary/no‑coverage or non‑formulary policy for the relevant line of business as listed below.

Formulary/no‑coverage policies: CP.CPA.190 (Commercial), HIM.PA.33 (Marketplace/ICHRA), CP.PMN.255 (Medicaid)
Non‑formulary policies: CP.CPA.190 (Commercial), HIM.PA.103 (Marketplace/ICHRA), CP.PMN.16 (Medicaid)

NCCN-supported off-label uses (e.g., MZL, Waldenström macroglobulinemia) are incorporated into the policy and require that prescribed regimens be FDA‑approved or recommended by NCCN; prescribers must submit supporting evidence for off-label dosing supported by practice guidelines or peer-reviewed literature.

Mantle cell lymphoma

MZLMarginal zone lymphoma

Added maximum dose criteria for concomitant use with CYP3A inducers and updated dosing limits (2Q 2024 annual review): standard dose limit 200 mg/day (2 tablets) and allowance up to 300 mg/day (3 tablets) with prescriber attestation of inability to avoid CYP3A inducers.

02.04.25added

Added NCCN compendium-based criteria for MZL and Waldenström macroglobulinemia (2Q 2025 annual review) and updated Appendix B example therapies.