ModifiedCentenePolicy CP.PHAR.620

Pirtobrutinib (Jaypirca) coverage

Defines medical necessity, prior authorization, and coverage criteria for pirtobrutinib (Jaypirca) for adults with CLL/SLL, mantle cell lymphoma, and select NCCN-compendium off-label indications for Centene lines of business.

Policy Summary

PayerCentene

PolicyPirtobrutinib (Jaypirca) coverage

Policy CodePolicy CP.PHAR.620

Change TypeMaterial revisions and additions (indications, dose limits, duration extension)

Effective Date06.01.23

Next Review DateN/A

Key ActionPrescriber must submit documentation and attestation for prior authorization, including evidence for dose >200 mg/day with concomitant CYP3A inducers.

SourceLink

POLICY UPDATE CHANGES

Added criteria for MZL and Waldenström macroglobulinemia per NCCN and updated Appendix B example therapies.

For CLL/SLL, updated FDA approved indications to full approval 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 for concomitant use with CYP3A inducers for all indications.

Added ICHRA line of business.

200 mgrecommended daily dose

200 mg/daystandard maximum dose

300 mg/daymax w/ attestation

Age ≥ 18

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50 mg,100 mgtablet strengths

05.26last review P&T

Coverage Criteria for Pirtobrutinib (Jaypirca)

Initial Therapy - CLL/SLL

Covered when ALL of the following are met:

CLL/SLL Initial Criteria: 1. Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Prescriber: 2. Prescribed by or in consultation with an oncologist or hematologist.

Age: 3. Patient is age ≥ 18 years.

Product selection: 4. For Jaypirca requests, member must use pirtobrutinib, if available, unless contraindicated or clinically significant adverse effects are experienced.

Prior therapy / transformation

Prior covalent BTK inhibitor: a. Member has received prior treatment with a covalent BTK inhibitor (e.g., zanubrutinib/Brukinsa, acalabrutinib/Calquence, ibrutinib/Imbruvica).
Prior authorization may be required.
Richter transformation (off-label): b. Member has histologic (Richter's) transformation to diffuse large B-cell lymphoma (off-label).

Monotherapy: 6. Jaypirca is prescribed as a single agent.

Dose limits

Standard dose: a. Dose does not exceed: i. 200 mg per day; ii. 2 tablets per day.200 mg/day
CYP3A inducer exception: b. Dose does not exceed: i. 300 mg per day; ii. 3 tablets per day; and iii. prescriber attestation that the member is unable to avoid concomitant use of a CYP3A inducer (e.g., carbamazepine, rifampin, ritonavir, St. John's wort).300 mg/day
Prescriber attestation required.
Guideline-supported dose: c. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use; prescriber must submit supporting evidence.

Initial Therapy - MCL

Covered when ALL of the following are met:

MCL Initial Criteria: 1. Diagnosis of mantle cell lymphoma (MCL).

Prescriber: 2. Prescribed by or in consultation with an oncologist or hematologist.

Age: 3. Patient is age ≥ 18 years.

Product selection: 4. For Jaypirca requests, member must use pirtobrutinib, if available, unless contraindicated or clinically significant adverse effects are experienced.

Prior lines of therapy: 5. Member has received ≥ 2 prior lines of therapy (see Appendix B).

NCCN Compendium Indications

Covered when ALL of the following are met:

NCCN Off-label Indications: 1. Diagnosis of one of the following as subsequent therapy: a. Marginal zone lymphoma (MZL) OR b. Waldenström macroglobulinemia/lymphoplasmacytic lymphoma.

Prescriber: 2. Prescribed by or in consultation with an oncologist or hematologist.

Age: 3. Patient is age ≥ 18 years.

Product selection: 4. For Jaypirca requests, member must use pirtobrutinib, if available, unless contraindicated or clinically significant adverse effects are experienced.

MZL prior therapy:

Initial Therapy / Coverage criteria (summarized)

Covered when ALL of the following are met (summary from document portions in this window):

Dose and indication: Member has a covered diagnosis (e.g., MCL, CLL, SLL; MZL and Waldenström additions per NCCN) and dosing consistent with product labeling (typical dose 200 mg PO QD for MCL, CLL, SLL).200 mg PO QD

Tablet strengths 50 mg and 100 mg available; maximum dose adjustments for concomitant CYP3A inducers applied.

Prior therapy requirements: For CLL/SLL, member has received prior treatment with a covalent BTK inhibitor; for MZL, prior covalent BTK inhibitor requirement clarified per recent review.prior covalent BTK inhibitor

Richter's transformation requirement simplified per NCCN compendium.

Authorization duration: Initial approval duration is 12 months (extended from 6 months).

Non‑FDA approved indications that are not specifically addressed in this policy are excluded from coverage unless the provider supplies sufficient documentation of efficacy and safety in accordance with the applicable off‑label use policies: CP.CPA.09 (Commercial), HIM.PA.154 (Health Insurance Marketplace/ICHRA), or CP.PMN.53 (Medicaid), or unless coverage is supported by the member's evidence of coverage documents.

Appendix C: Contraindications/Boxed Warnings — None reported.

Use of pirtobrutinib (Jaypirca) for indications outside the FDA‑approved labeling and the NCCN compendium is not authorized unless the request is supported by sufficient clinical documentation per the applicable off‑label use policies referenced in this policy (see CP.CPA.09, HIM.PA.154, CP.PMN.53) or coverage is established by the member's benefit documents.

This clinical policy is intended as a guide to medical necessity to assist in coverage determinations and benefit administration. It does not itself guarantee payment. Providers are expected to exercise professional medical judgment and follow all applicable coverage documents, state and federal requirements, and Health Plan administrative policies when submitting requests for pirtobrutinib.

Initial Therapy — Requirements and Dosing

Initial Therapy — Initial coverage rules

Covered when ALL of the following are met:

Prescriber specialty and age: 1. Prescribed by or in consultation with an oncologist or hematologist; patient is age ≥ 18 years.

Appropriate diagnosis: 2. Diagnosis corresponds to a covered indication (CLL, SLL, MCL, or NCCN-compendium indications such as MZL or Waldenström macroglobulinemia where specified).

Product selection: 3. For Jaypirca requests, member must use pirtobrutinib, if available, unless contraindicated or clinically significant adverse effects are experienced.

Prior therapy requirements (by diagnosis)

Continuation and Renewal Criteria

Continuation Therapy — Continuation/Renewal criteria

Covered when ALL of the following are met:

Current therapy documentation: 1. Member is currently receiving Jaypirca via the Centene benefit, or documentation supports that member has received Jaypirca for at least 30 days for a covered indication.≥ 30 days

Clinical response: 2. Member is responding positively to therapy (clinical benefit documented).

Product selection: 3. For Jaypirca requests, member must use pirtobrutinib, if available, unless contraindicated or clinically significant adverse effects are experienced.

Dose change rules

Dosing Limits and Coding-related Notes

Dose limits

Standard maximum daily dose200 mg/day (2 tablets)

Permitted maximum with CYP3A inducer attestation300 mg/day (3 tablets) when prescriber attests member cannot avoid concomitant CYP3A inducer

Alternative justification for higher doseDose supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence)

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization may be required for Jaypirca (pirtobrutinib). Prescribers must attest that the member meets all applicable clinical criteria in this policy and must provide supporting documentation when requested. Requests should include relevant office chart notes, laboratory results, and any other clinical information necessary to demonstrate that approval criteria are met.

Affected drugs: Jaypirca (pirtobrutinib)
Supporting documentation: office notes, labs, pathology, prior therapy records
Prescriber requirement: oncologist or hematologist involvement for indicated diagnoses

Documentation Required

Documentation Requirements

Provider must submit documentation (such as office chart notes, laboratory results, or other clinical information) supporting that the member has met all approval criteria. The Health Plan may request additional information to determine medical necessity; failure to provide requested documentation may result in denial of the request.

Step Therapy and Preferred Alternatives

Therapeutic alternative / example	Notes (coverage / prior auth implications)
BTK inhibitors (acalabrutinib [Calquence], zanubrutinib [Brukinsa], ibrutinib [Imbruvica])	Listed in Appendix B as example therapies; may be recommended alternatives and may require prior authorization per individual formulary.
Bendamustine + rituximab	Example regimen included in Appendix B; dosing/regimen varies by indication and may require prior authorization.
Bortezomib-based regimens (e.g., VR-CAP)	Included among Appendix B examples for MCL; may be considered before Jaypirca per therapy sequencing and could require prior authorization.
Cytotoxic combination regimens (NORDIC, TRIANgLE, LyMA, GemOx, RBAC500)	Multiple first-line and subsequent regimens shown in Appendix B as examples; selection guided by NCCN and may affect step therapy decisions/prior authorization requirements.
Venetoclax (Venclexta) ± rituximab	Listed in Appendix B examples; may be an alternative regimen and could require prior authorization depending on benefit and indication.
Lenalidomide (Revlimid) + rituximab	Included in Appendix B example therapies; may be preferred alternative and subject to prior authorization per plan rules.

Step	Therapy sequencing / requirement
1	Therapy sequencing reflects NCCN-referenced alternatives; Appendix B lists therapeutic alternatives that may be considered prior to Jaypirca; choices guided by NCCN recommendations.
1a	For certain indications (e.g., CLL/SLL, MCL), prior treatment with a covalent BTK inhibitor is required before pirtobrutinib (Jaypirca) per updated criteria.
1b	For MCL specifically, member must have received ≥2 prior lines of systemic therapy (including a BTK inhibitor) consistent with indicational requirements referenced in the policy and NCCN examples.
Notes	Appendix B alternatives may themselves require prior authorization; specific step-failure or trial requirements are based on NCCN sequencing and plan prior authorization rules rather than a single prescriptive step-failure algorithm in this section.

Definitions and Acronyms

BTK

BTKBruton tyrosine kinase

Class descriptionPirtobrutinib (Jaypirca) is a noncovalent BTK inhibitor

Related drug classBTK inhibitors (covalent and noncovalent) referenced in prior therapy requirements

Acronyms

CLLchronic lymphocytic leukemia

MCLmantle cell lymphoma

MZLmarginal zone lymphoma

Background

Pirtobrutinib (Jaypirca) is a noncovalent Bruton tyrosine kinase (BTK) inhibitor indicated in this policy for certain relapsed/refractory lymphoid malignancies. The policy covers relapsed/refractory mantle cell lymphoma (MCL) after ≥2 systemic therapies including a BTK inhibitor, and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) previously treated with a covalent BTK inhibitor; selected NCCN‑compendium subsequent‑therapy indications (e.g., marginal zone lymphoma and Waldenström macroglobulinemia) are addressed per NCCN guidance. Prior authorization and supporting documentation are required per the criteria in this policy.

Site of Care

Note

No site‑of‑care limitation specified

No specific site-of-care restrictions are stated in this policy; authorization and documentation requirements apply regardless of treatment setting.

Submit required documentation (office notes, labs) as part of prior authorization regardless of site of administration.

Revision History

2026-03-31annual_reviewLatest

2Q 2026 annual review: clarified prior therapy requirement for MZL to require a covalent BTK inhibitor; references reviewed and updated; added ICHRA line of business.

2025-02-04annual_review

2Q 2025 annual review: added criteria for MZL and Waldenström macroglobulinemia per NCCN and updated Appendix B example therapies; references reviewed and updated.

2025-12-12material_revision

Updated CLL/SLL FDA indication to full approval and simplified prior therapy requirement to 'Member has received prior treatment with a covalent BTK inhibitor'; simplified Richter's transformation requirement per NCCN; extended initial approval duration from 6 to 12 months.

Policy Summary

PayerCentene

PolicyPirtobrutinib (Jaypirca) coverage

Policy CodePolicy CP.PHAR.620

Change TypeMaterial revisions and additions (indications, dose limits, duration extension)

Effective Date06.01.23

Next Review DateN/A

Key ActionPrescriber must submit documentation and attestation for prior authorization, including evidence for dose >200 mg/day with concomitant CYP3A inducers.

SourceLink

On This Page

Prior BTK inhibitor: 6. Member has received prior treatment with a BTK inhibitor (e.g., ibrutinib/Imbruvica, zanubrutinib/Brukinsa, acalabrutinib/Calquence).

Prior authorization may be required.

Dose limits

Standard dose: a. Dose does not exceed: i. 200 mg per day; ii. 2 tablets per day.200 mg/day
CYP3A inducer exception: b. Dose does not exceed: i. 300 mg per day; ii. 3 tablets per day; and iii. prescriber attestation that the member is unable to avoid concomitant use of a CYP3A inducer (e.g., carbamazepine, rifampin, ritonavir, St. John's wort).300 mg/day
Prescriber attestation required.
Guideline-supported dose: c. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use; prescriber must submit supporting evidence.

5. For MZL, member has received prior treatment with a covalent BTK inhibitor (e.g., ibrutinib, zanubrutinib, acalabrutinib).

prior covalent BTK inhibitor

Dose limits

Standard dose: a. Dose does not exceed: i. 200 mg per day; ii. 2 tablets per day.200 mg/day
CYP3A inducer exception: b. Dose does not exceed: i. 300 mg per day; ii. 3 tablets per day; and iii. prescriber attestation that the member is unable to avoid concomitant use of a CYP3A inducer (e.g., carbamazepine, rifampin, ritonavir, St. John's wort).300 mg/day
Prescriber attestation required.
Guideline-supported dose: c. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use; prescriber must submit supporting evidence.

Continuation/renewal criteria referenced elsewhere in policy.

CLL/SLL prior BTK: a. For CLL/SLL: Member has received prior treatment with a covalent BTK inhibitor (or has Richter's transformation per simplified NCCN criteria).prior covalent BTK inhibitor

MCL prior lines/BTK: b. For MCL: Member has received ≥ 2 prior lines of systemic therapy and prior treatment with a BTK inhibitor.≥ 2 prior lines; prior BTK

See Appendix B for examples of prior therapies.

MZL prior BTK: c. For MZL (NCCN compendium): Member has received prior treatment with a covalent BTK inhibitor as specified in updates.prior covalent BTK inhibitor

Dose limits and exceptions

Standard dose: a. Dose ≤ 200 mg per day (2 tablets).≤ 200 mg/day
Tablet strengths: 50 mg, 100 mg.
CYP3A exception: b. Dose ≤ 300 mg per day (3 tablets) with prescriber attestation of inability to avoid concomitant CYP3A inducer (e.g., carbamazepine, rifampin, ritonavir, St. John's wort).≤ 300 mg/day
Prescriber attestation required.
Guideline-supported dose: c. Dose supported by practice guidelines or peer-reviewed literature for the off-label use with submitted supporting evidence.

Initial Therapy — Initial therapy dosing and authorization notes present in document

Recommended dose and formulation: 1. Recommended dosing for MCL, CLL, and SLL: 200 mg orally once daily (200 mg/day).200 mg/day

Tablet strengths available: 50 mg and 100 mg.

Maximum dose with CYP3A inducers: 2. Maximum dose may be increased to 300 mg per day (3 tablets) only when prescriber attests the member cannot avoid concomitant CYP3A inducers or when supported by guidelines/peer-reviewed literature; prescriber must submit attestation or supporting evidence as applicable.300 mg/day

2Q 2024 annual review added maximum dose criteria for concomitant CYP3A inducers.

Authorization notes: 3. Prior authorization may be required; prescriber must attest to criteria and provide documentation when requested (e.g., for dose >200 mg/day or off-label use supported by literature).

Appendix B lists therapeutic alternatives per NCCN; see policy for documentation requirements and examples.

Standard dose increase: a. New dose does not exceed: i. 200 mg per day; ii. 2 tablets per day.≤ 200 mg/day

CYP3A exception for increase: b. New dose does not exceed: i. 300 mg per day; ii. 3 tablets per day; and iii. prescriber attestation that the member is unable to avoid concomitant use of a CYP3A inducer.≤ 300 mg/day

Prescriber attestation required.

Guideline-supported increase: c. New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use; prescriber must submit supporting evidence.

Continuation Therapy — Renewal criteria

Minimum duration on therapy: 1. Member must have been on therapy for at least 30 days prior to renewal request.≥ 30 days

Response to therapy: 2. Member must be responding positively to therapy; clinical documentation should support continued benefit.

Dose and duration rules: 3. Renewal requests must adhere to dose limits (standard 200 mg/day; 300 mg/day allowed with attestation or guideline support).200 mg/day; 300 mg/day with attestation

Approval duration: Medicaid/HIM/ICHRA 12 months; Commercial 12 months or duration of request, whichever is less.

Continuation Therapy — Continuation/renewal context

Continuation/renewal context: 1. Initial approval duration has been extended to 12 months; continuation criteria require documentation of ongoing benefit and adherence to dosing rules.12 months

Continuation rules are referenced elsewhere in the policy and in Appendix B for therapeutic alternatives.

Examples of acceptable documentation: progress notes, treatment history, pathology reports, imaging, medication administration records
Include evidence supporting off‑label use when applicable (see off‑label policy references)

Note

General Policy and Administrative Notes

Coverage decisions are guides to medical necessity and do not guarantee payment. Providers are expected to exercise professional medical judgment and to follow applicable Health Plan coverage terms, evidence of coverage, and state/federal requirements. For Medicaid members, state Medicaid coverage provisions take precedence over this clinical policy when conflicts exist.

This policy is developed from current standards of practice and evidence but is not a contract or guarantee of payment
Providers must adhere to plan-specific benefit terms, exclusions, and administrative policies

National Comprehensive Cancer Network

NCCNNational Comprehensive Cancer Network

RoleSource of recommended regimens and compendium indications referenced in prescribing criteria

Citation in policyPrescribed regimen must be FDA‑approved or recommended by NCCN

small lymphocytic lymphoma

SLLsmall lymphocytic lymphoma

Relation to CLLSLL is listed alongside CLL as an FDA‑approved indication for Jaypirca

Abbreviation sourceDefined in Appendix A abbreviation/acronym key