mhn pirtobrutinib (Jaypirca) Coverage Update

Coverage and Medical Necessity Criteria

Initial Therapy — CLL/SLL

Covered when ALL of the following are met

CLL/SLL initial therapy criteria: 1) Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL); 2) Prescribed by or in consultation with an oncologist or hematologist; 3) Age ≥ 18 years; 4) Member will use pirtobrutinib (Jaypirca) when available unless contraindicated or clinically significant adverse effects are experienced; 5) One of the following: a) Member has received prior treatment with a covalent BTK inhibitor (e.g., Brukinsa, Calquence, Imbruvica); OR b) Member has histologic (Richter's) transformation to diffuse large B‑cell lymphoma (off‑label); 6) Jaypirca is prescribed as a single agent; 7) Request meets one of the following dosing conditions: a) Dose does not exceed 200 mg per day and 2 tablets per day; OR b) Dose does not exceed 300 mg per day and 3 tablets per day with prescriber attestation that the member cannot avoid concomitant use of a CYP3A inducer (e.g., carbamazepine, rifampin, ritonavir, St. John's wort); OR c) Dose is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence).age >=18; dose <=200 mg/day standard; up to 300 mg/day with CYP3A attestation

Prescribed regimen must be FDA‑approved or recommended by NCCN.

Initial Therapy — Mantle Cell Lymphoma

Covered when ALL of the following are met

MCL initial therapy criteria: 1) Diagnosis of mantle cell lymphoma (MCL); 2) Prescribed by or in consultation with an oncologist or hematologist; 3) Age ≥ 18 years; 4) Member will use pirtobrutinib (Jaypirca) when available unless contraindicated or clinically significant adverse effects are experienced; 5) Member has received ≥ 2 prior lines of systemic therapy; 6) Member has received prior treatment with a BTK inhibitor (e.g., Imbruvica, Brukinsa, Calquence); 7) Request meets one of the following dosing conditions: a) Dose does not exceed 200 mg per day and 2 tablets per day; OR b) Dose does not exceed 300 mg per day and 3 tablets per day with prescriber attestation that the member cannot avoid concomitant use of a CYP3A inducer (e.g., carbamazepine, rifampin, ritonavir, St. John's wort); OR c) Dose is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence).>=2 prior lines for MCL; age >=18; dose thresholds as above

Prescribed regimen must be FDA‑approved or recommended by NCCN.

Initial Therapy — NCCN Compendium Indications

Covered when ALL of the following are met

NCCN compendium off-label indications: 1) Diagnosis of one of the following: a) Marginal zone lymphoma (MZL) as subsequent therapy; OR b) Waldenström macroglobulinemia/lymphoplasmacytic lymphoma as subsequent therapy; 2) Prescribed by or in consultation with an oncologist or hematologist; 3) Age ≥ 18 years; 4) Member will use pirtobrutinib (Jaypirca) when available unless contraindicated or clinically significant adverse effects are experienced; 5) For MZL, member has received prior treatment with a BTK inhibitor (e.g., Imbruvica, Brukinsa, Calquence); 6) Request meets one of the following dosing conditions: a) Dose does not exceed 200 mg per day and 2 tablets per day; OR b) Dose does not exceed 300 mg per day and 3 tablets per day with prescriber attestation that the member cannot avoid concomitant use of a CYP3A inducer (e.g., carbamazepine, rifampin, ritonavir, St. John's wort); OR c) Dose is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence).age >=18; prior BTK for MZL; dose thresholds as above

Prescribed regimen must be FDA‑approved or recommended by NCCN.

Continuation Therapy

Covered when ALL of the following are met

Continuation therapy criteria: 1) Member is currently receiving Jaypirca via the Centene benefit or documentation supports member has been receiving Jaypirca for a covered indication for at least 30 days; 2) Member is responding positively to therapy; 3) Member will use pirtobrutinib (Jaypirca) when available unless contraindicated or clinically significant adverse effects are experienced; 4) If request is for a dose increase, the new dose meets one of the following: a) New dose does not exceed 200 mg per day and 2 tablets per day; OR b) New dose does not exceed 300 mg per day and 3 tablets per day with prescriber attestation that the member cannot avoid concomitant use of a CYP3A inducer (e.g., carbamazepine, rifampin, ritonavir, St. John's wort); OR c) New dose is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence).>=30 days on therapy; positive response required; dose thresholds as above

Prescribed regimen must be FDA‑approved or recommended by NCCN.

Initial and ongoing coverage criteria

Covered when ALL of the following are met

Indication: Member has diagnosis of an indicated B‑cell malignancy (MCL, CLL, SLL; later updates add MZL and Waldenström macroglobulinemia per NCCN).

References: prescribing information and NCCN compendia

Prior therapy: For CLL/SLL, member has received prior treatment with a covalent BTK inhibitor per updated prescribing information (simplified prior therapy requirement).

BRUIN study and NCCN supported uses cited

Dosing consistent with product labeling (typical dosing 200 mg PO once daily; tablet strengths 50 mg and 100 mg) and maximum dose adjustments for concomitant CYP3A inducers applied per policy (dose thresholds: ≤200 mg/day standard; ≤300 mg/day with prescriber attestation).200 mg PO QD typical

Initial approval duration extended to 12 months

Requests for pirtobrutinib (Jaypirca) for non‑FDA approved indications not addressed in this policy are not authorized unless the provider submits sufficient documentation demonstrating efficacy and safety in accordance with the applicable off‑label use policies: CP.CPA.09 (Commercial), HIM.PA.154 (Health Insurance Marketplace), or CP.PMN.53 (Medicaid), or unless there is supporting evidence of coverage. Providers should include clinical rationale, supporting literature or compendia references, and relevant patient records when requesting coverage for off‑label uses.

Appendix C lists contraindications and boxed warnings for pirtobrutinib (Jaypirca). None reported. Reviewers should confirm there are no updated contraindications or boxed warnings in the most recent prescribing information or compendia when evaluating requests.

Line of Therapy Specifications

second-line | subsequent

Line of therapy mapping: - CLL/SLL: for patients previously treated with a covalent BTK inhibitor. - MCL: relapsed/refractory after at least two lines of systemic therapy including a BTK inhibitor. - MZL and Waldenström: subsequent therapy per NCCN compendium.

second-line | subsequent (alternate)

Line: Indicated for previously treated/relapsed or refractory B‑cell malignancies; for CLL/SLL prior covalent BTK inhibitor required per updated labeling.

Provider Requirements, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for Jaypirca (pirtobrutinib). Providers must obtain prior authorization and submit documentation that the member meets the applicable clinical criteria (office chart notes, lab results, discharge summaries, or other clinical information). For indications requiring prior therapy (for example, CLL/SLL or MCL), documentation must include prior treatments and dosing details (e.g., prior covalent BTK inhibitor for CLL/SLL).

PA required prior to initiation
Include documentation of prior therapies and indication
Provide dosing information when relevant

Denial Risk

Off‑Label Requests Lacking Required Documentation

Requests for off‑label or non‑FDA approved indications that are not otherwise addressed in this policy may be denied unless the prescriber submits sufficient supporting documentation per the applicable off‑label use policies (e.g., CP.CPA.09 for Commercial, HIM.PA.154 for Health Insurance Marketplace, CP.PMN.53 for Medicaid) or evidence of coverage documents. Documentation should demonstrate efficacy and safety for the requested off‑label use and align with recognized compendia or peer‑reviewed literature.

Therapeutic Alternatives and Example Regimens (Appendix B)

Regimen / Class	Example Agents / Combination	Notes / Dosing (as listed)
HyperCVAD + rituximab	cyclophosphamide, vincristine, doxorubicin, dexamethasone / methotrexate / cytarabine + rituximab	Dosing regimen = Varies
NORDIC	rituximab + cyclophosphamide, vincristine, doxorubicin, prednisone / rituximab + cytarabine	Dosing regimen = Varies
TRAINGLE (RCHOP + RDHAP)	RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) + RDHAP (rituximab, dexamethasone, cytarabine) ± platinum	Dosing regimen = Varies
LyMA (RDHAP + platinum)	RDHAP (rituximab, dexamethasone, cytarabine) + platinum (cisplatin, oxaliplatin, or carboplatin)	Dosing regimen = Varies
BTK inhibitor–based regimens	acalabrutinib (Calquence), zanubrutinib (Brukinsa) ± anti-CD20 or venetoclax combinations	Dosing regimen = Varies
Bendamustine-based	bendamustine (Bendeka) + rituximab	Dosing regimen = Varies
Bortezomib-based	bortezomib (Velcade) ± rituximab	Dosing regimen = Varies
DHA + platinum + rituximab	dexamethasone, cytarabine + platinum (carboplatin, cisplatin, or oxaliplatin) + rituximab	Dosing regimen = Varies
GemOx + rituximab	gemcitabine, oxaliplatin + rituximab	Dosing regimen = Varies
Lenalidomide-based	lenalidomide (Revlimid) + rituximab	Dosing regimen = Varies
RBAC500	rituximab, bendamustine, cytarabine	Dosing regimen = Varies

Regimen / Class	Example Agents / Combination	Notes / Dosing (as listed)
BTK inhibitor combinations	ibrutinib (Imbruvica) + venetoclax (Venclexta); ibrutinib ± rituximab	Dosing regimen = Varies
Zanubrutinib / Acalabrutinib combinations	zanubrutinib (Brukinsa) / acalabrutinib (Calquence) + obinutuzumab (Gazyva) ± venetoclax	Dosing regimen = Varies
Bendamustine + rituximab	bendamustine (Bendeka) + rituximab	Dosing regimen = Varies
Bortezomib-based regimens	bortezomib (Velcade) ± rituximab	Dosing regimen = Varies
Venetoclax combinations	venetoclax (Venclexta) ± rituximab or with BTK inhibitor	Dosing regimen = Varies
Immunochemotherapy / cytarabine regimens	RDHAP, GemOx, RBAC500 and similar regimens including rituximab + cytarabine/platinum	Dosing regimen = Varies

Acronyms and Terms

BTK — Bruton tyrosine kinase

TermBTK

DefinitionBruton tyrosine kinase

ContextTargeted kinase involved in B-cell receptor signaling; relevant to B-cell malignancies treated with BTK inhibitors

CLL — chronic lymphocytic leukemia

AbbreviationCLL

Definitionchronic lymphocytic leukemia

Policy contextFDA‑approved indication updated to require prior treatment with a covalent BTK inhibitor for CLL/SLL per recent RT4 update

Authorization Duration and Product Strengths

Initial approval duration — 12 months

Initial approval duration12 months

Typical dosing referenceTypical dosing listed as 200 mg PO once daily in Dosage and Administration

Policy change noteInitial approval duration was extended from 6 to 12 months in the RT4 update dated 12.12.25

Drug Background and Context

Pirtobrutinib (Jaypirca) is a noncovalent Bruton tyrosine kinase (BTK) inhibitor200 mg orally once daily with tablet strengths available to support that regimen. Providers should reference the current prescribing information and NCCN compendia for complete mechanism, indications, and dosing guidance when submitting requests.

Policy Revision History

2025-12-12RT4 updateLatest

For CLL/SLL, FDA approved indication text updated to reflect conversion from accelerated to full approval; prior therapy requirement simplified to 'Member has received prior treatment with a covalent BTK inhibitor'; initial approval duration extended from 6 to 12 months.

2025-02-042Q 2025 annual review

Added criteria for marginal zone lymphoma (MZL) and Waldenström macroglobulinemia per NCCN and updated example therapies in Appendix B.

2024-02-12