CurrentViva HealthPolicy IC-0007

Pemetrexed (Alimta, Pemrydi, Pemfexy) — Intravenous therapy coverage

Clinical coverage and prior authorization requirements for intravenous pemetrexed formulations for oncology indications for Viva Health members in North Carolina and providers seeking authorization.

Policy Summary

PayerViva Health

PolicyPemetrexed (Alimta, Pemrydi, Pemfexy) — Intravenous therapy coverage

Policy CodePolicy IC-0007

Change TypeNo material clinical or coverage changes

Effective DateSep 4, 2025

Next Review DateSep 4, 2025

Key ActionObtain prior authorization — initial approvals generally provided for 6 months (some indications specify 6 cycles or 6 doses).

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

6 monthsInitial auth duration

500 mg/m2Common dose (NS-NSCLC etc.)

900 mg/m2Dose (CNS lymphoma)

≥ 11HCPCS codes listed

~70+Covered ICD-10 list

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Initial Therapy Indications

Covered when ALL of the following are met:

Core eligibility: Patient is at least 18 years of age>=18 years

CNS cancers: Primary CNS lymphoma (including vitreoretinal/PCNSL ocular variant) as single-agent induction if unsuitable for high-dose methotrexate, or for relapsed/refractory disease; OR limited or extensive brain metastases from EGFR-sensitizing mutation–positive NSCLC (confirmed by FDA-approved or CLIA-compliant test) when used in combination with specified agents for defined clinical scenarios; OR leptomeningeal metastases from EGFR mutation–positive NSCLC (confirmed by FDA-approved or CLIA-compliant test) as single-agent intra‑CSF for primary or maintenance treatment in patients meeting risk/stability criteriaper indication

See detailed agent combinations and clinical scenarios

Cervical cancer: Used as subsequent therapy for recurrent or metastatic squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma as a single agentrecurrent/metastatic

Peritoneal mesothelioma (PeM): Adjuvant following CRS+HIPEC for patients with surgical/pathologic high‑risk features; OR first‑line when inoperable or complete cytoreduction not achievable or disease progressed after CRS+HIPEC without prior adjuvant systemic therapy; OR subsequent therapy including rechallenge after prior pemetrexed response — as single agent or combined with platinum chemotherapy with or without bevacizumab or pembrolizumab depending on scenarioper indication

High‑risk features include Ki‑67 >9%, nodal metastasis, thrombocytosis, PS=2, PCI >17, CC score >1, biphasic/sarcomatoid histology, or bicavitary disease

Pleural mesothelioma (PM): Used as induction prior to surgical exploration for clinical stage I epithelioid histology; OR used as first‑line therapy; OR used as subsequent therapy — as single agent or in combination with platinum chemotherapy with or without bevacizumab or pembrolizumab per scenario; rechallenge allowed after prior pemetrexed‑based responseper indication

Non‑squamous NSCLC: Used in combination with cisplatin or carboplatin-containing regimens, or with bevacizumab/pembrolizumab/cemiplimab/durvalumab for continuation maintenance if previously used first‑line; OR used as single agent for recurrent/advanced/metastatic disease; OR used first‑line for tumors negative for actionable molecular biomarkers or for tumors with specified driver alterations (EGFR exon 20 insertion, BRAF V600E, NTRK fusions, MET exon 14 skipping, NRG1 fusion, ERBB2/HER2 mutation); OR used as subsequent therapy or continuation/switch maintenance — complete genotyping for actionable markers is recommendedper indication; genotyping recommended

Actionable biomarkers include EGFR, KRAS, ALK, ROS1, BRAF, NTRK1/2/3, MET, RET, NRG1, ERBB2 (HER2)

Thymomas and thymic carcinomas: Used as a single agent when patient is unable to tolerate first‑line combination regimens; may be used preoperatively if R0 resection is uncertain; postoperative after R1/R2 resection (carcinoma only); first‑line for recurrent/advanced/metastatic disease; or second‑line for unresectable/metastatic diseaseper indication

Ovarian, fallopian tube, primary peritoneal cancer: Used as a single agent for recurrent or persistent Grade 1 endometrioid carcinoma, carcinosarcoma (malignant mixed Müllerian tumor), mucinous ovarian neoplasms, epithelial ovarian/fallopian tube/primary peritoneal cancer, or clear cell carcinoma of the ovary; NOT indicated for immediate biochemical relapse (rising CA‑125 without radiographic evidence)recurrent/persistent with radiographic disease

Vaginal cancer: Used as a single agent as subsequent therapy for recurrent or metastatic diseaserecurrent/metastatic

Thyroid carcinoma: Used in combination with carboplatin for follicular or papillary unresectable/locoregional recurrent or metastatic RAI‑refractory progressive disease; used for oncocytic carcinoma with unresectable/metastatic progressive disease after prior treatment; anaplastic carcinoma as second‑line therapy for stage IVC diseaseper histology and prior therapy

Pemetrexed is not indicated for treatment of immediate biochemical relapse in ovarian, fallopian tube, or primary peritoneal cancer — defined as a rising CA-125 level without radiographic evidence of disease. Coverage for these tumor types requires radiographic or clinical evidence of recurrent or persistent disease rather than biochemical-only progression.

Renewal of prior authorization requires that the patient continue to meet the indication-specific criteria and that the duration of authorization has not been exceeded. Requests will be denied/ not renewed if there is unacceptable toxicityCrCl <45 mL/min, bullous/exfoliative skin reactions, interstitial pneumonitis, or other listed serious adverse events. Continued authorization also requires evidence of disease benefit (stabilization or tumor reduction).

Parameter	Details
Typical dose for non-squamous NSCLC, mesothelioma, thymic malignancies, and thyroid carcinoma
Administer up to 500 mg/m2 IV every 21 days; for mesotheliomas: 500 mg/m2 IV q21d (6 cycles when given with bevacizumab + platinum; 6 doses when given with pembrolizumab + platinum); thymomas/thymic carcinomas: 500 mg/m2 IV q21d for a maximum of 6 cycles
Dose for primary CNS lymphoma
Administer 900 mg/m2 IV every 21 days; continue until disease progression or unacceptable toxicity
Dose for ovarian, fallopian tube, primary peritoneal cancer, cervical cancer, and vaginal cancer
Administer up to 900 mg/m2 IV every 21 days until disease progression or unacceptable toxicity; (leptomeningeal metastases from NSCLC have distinct scheduling)
Renal function / CrCl limits and precautions
Avoid ibuprofen for 2 days before, the day of, and 2 days after administration in patients with CrCl <80 mL/min; do not administer if CrCl <45 mL/min
Supplementation
Supplement with oral folic acid and intramuscular vitamin B12
Billing units / max billable units (example by product and indication)
Pemfexy (500 mg MDV): Primary CNS lymphoma, cervical, vaginal, ovarian/fallopian tube/peritoneal cancer — 225 billable units q21d; Leptomeningeal NSCLC — 5 units on day 1 and 5 of a 7-day cycle then 5 units q21d; Thymomas, NS-NSCLC, Mesotheliomas, Thyroid, brain metastases — 125 billable units q21d. Other manufacturers (SDV): corresponding limits — 230 units q21d (selected tumors), 10 units on day 1 and 5 then 10 units q21d for leptomeningeal disease, and 130 units q21d for thymomas/NS-NSCLC/mesothelioma/thyroid/brain metastases

Coding: HCPCS, J-Codes, and Diagnosis Codes

Covered HCPCS CodesHCPCSCovered

J9305	Pemetrexed Disodium Lyophilisate for injection (Alimta)
J9322	Pemetrexed Disodium Lyophilisate for injection (BluePoint brand HCPCS)
J9324	Pemetrexed Disodium Hemipentahydrate Solution for injection (Pemrydi RTU)
J9294	Pemetrexed Disodium Solution for injection (Hospira) HCPCS
J9296	Pemetrexed Disodium Solution for injection (Accord) HCPCS
J9297	Pemetrexed Disodium Solution for injection (Sandoz) HCPCS

Covered HCPCS J-codesHCPCSCovered

J9292	Injection, pemetrexed dipotassium, 10 mg
J9294	Injection, pemetrexed (hospira), not therapeutically equivalent to J9305, 10 mg
J9296	Injection, pemetrexed (accord), not therapeutically equivalent to J9305, 10 mg
J9297	Injection, pemetrexed (sandoz), not therapeutically equivalent to J9305, 10 mg
J9304	Injection, pemetrexed (pemfexy), 10 mg
J9305	Injection, pemetrexed, not otherwise specified, 10 mg
J9314	Injection, pemetrexed (teva), not therapeutically equivalent to J9305, 10 mg
J9322	Injection, pemetrexed (bluepoint), not therapeutically equivalent to J9305, 10 mg
J9323	Injection, pemetrexed ditromethamine, 10 mg
J9324	Injection, pemetrexed (pemrydi rtu), 10 mg

1–10 of 11

1/2

Covered ICD-10 diagnosis codesICD-10Covered

C33	Malignant neoplasm of trachea
C34.00	Malignant neoplasm of unspecified main bronchus
C34.01	Malignant neoplasm of right main bronchus
C34.02	Malignant neoplasm of left main bronchus
C34.10	Malignant neoplasm of upper lobe, unspecified bronchus or lung
C34.11	Malignant neoplasm of upper lobe, right bronchus or lung
C34.12	Malignant neoplasm of upper lobe, left bronchus or lung
C34.2	Malignant neoplasm of middle lobe, bronchus or lung
C34.30	Malignant neoplasm of lower lobe, unspecified bronchus or lung
C34.31	Malignant neoplasm of lower lobe, right bronchus or lung

1–10 of 26

1/3

Covered ICD-10 Codes (selected - lung, thymus, mesothelioma)ICD-10Covered

C33	Malignant neoplasm of trachea.
C34.00	Malignant neoplasm of unspecified main bronchus.
C34.01	Malignant neoplasm of right main bronchus.
C34.02	Malignant neoplasm of left main bronchus.
C34.10	Malignant neoplasm of upper lobe, unspecified bronchus or lung.
C34.11	Malignant neoplasm of upper lobe, right bronchus or lung.
C34.12	Malignant neoplasm of upper lobe, left bronchus or lung.
C34.2	Malignant neoplasm of middle lobe, bronchus or lung.
C34.30	Malignant neoplasm of lower lobe, unspecified bronchus or lung.
C34.31	Malignant neoplasm of lower lobe, right bronchus or lung.

1–10 of 20

1/2

Covered ICD-10 Codes (mesothelioma / peritoneum)ICD-10Covered

C45.2	Mesothelioma of pericardium.
C45.7	Mesothelioma of other sites.
C45.9	Mesothelioma, unspecified.
C48.1	Malignant neoplasm of specified parts of peritoneum.
C48.2	Malignant neoplasm of peritoneum, unspecified.
C48.8	Malignant neoplasm of overlapping sites of retroperitoneum and peritoneum.

Covered ICD-10 Codes (female genital organs, thyroid)ICD-10Covered

C52	Malignant neoplasm of vagina.
C53.0	Malignant neoplasm of endocervix.
C53.1	Malignant neoplasm of exocervix.
C53.8	Malignant neoplasm of overlapping sites of cervix uteri.
C53.9	Malignant neoplasm of cervix uteri, unspecified.
C56.1	Malignant neoplasm of right ovary.
C56.2	Malignant neoplasm of left ovary.
C56.3	Malignant neoplasm of bilateral ovaries.
C56.9	Malignant neoplasm of unspecified ovary.
C57.00	Malignant neoplasm of unspecified fallopian tube.

1–10 of 24

1/3

Covered ICD-10 Codes (secondary neoplasms, lymphomas, thymus, history codes)ICD-10Covered

C79.31	Secondary malignant neoplasm of brain.
C79.32	Secondary malignant neoplasm of cerebral meninges.
C83.30	Diffuse large B-cell lymphoma unspecified site.
C83.390	Primary central nervous system lymphoma.
C83.398	Diffuse large B-cell lymphoma of other extranodal and solid organ sites.
C83.59	Lymphoblastic (diffuse) lymphoma, extranodal and solid organ sites.
C83.79	Burkitt lymphoma, extranodal and solid organ sites.
C83.80	Other non-follicular lymphoma, unspecified site.
C83.89	Other non-follicular lymphoma, extranodal and solid organ sites.
C84.49	Peripheral T-cell lymphoma, not elsewhere classified, extranodal and solid organ sites.

1–10 of 18

1/2

Medicare Part B Covered Diagnosis CodesICD-10

N/A	Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/LCA): N/A

Max billable units (selected indications)

Pemfexy (500 mg MDV) — CNS/gynecologic indications225 billable units every 21 days for primary CNS lymphoma, cervical, vaginal, ovarian, fallopian tube, and primary peritoneal cancers

Pemfexy (500 mg MDV) — leptomeningeal NSCLC5 billable units on day 1 and day 5 of a 7-day cycle, then 5 units every 21 days

Pemfexy (500 mg MDV) — NSCLC/mesothelioma/thyroid/brain mets125 billable units every 21 days for thymomas/thymic carcinomas, non-squamous NSCLC, mesotheliomas, thyroid carcinoma, and limited or extensive brain metastases

Pemetrexed (other manufacturers) SDV — CNS/gynecologic indications230 billable units every 21 days for primary CNS lymphoma, cervical, vaginal, ovarian, fallopian tube, and primary peritoneal cancers

Pemetrexed (other manufacturers) SDV — leptomeningeal NSCLC10 billable units on day 1 and day 5 of a 7-day cycle, then 10 units every 21 days

Pemetrexed (other manufacturers) SDV — NSCLC/mesothelioma/thyroid/brain mets130 billable units every 21 days for thymomas/thymic carcinomas, non-squamous NSCLC, mesotheliomas, thyroid carcinoma, and limited or extensive brain metastases

Provider Actions, Prior Authorization, and Billing Requirements

Prior Authorization

Prior Authorization Validity

Prior authorization is required for this drug. Initial approvals are generally provided for 6 months unless an indication specifies otherwise (examples: thymomas/thymic carcinomas — initial approval for six cycles; certain mesothelioma combinations — initial approval for six cycles or six doses as specified). Renewals may be granted every 6 months unless the indication or safety rules prohibit renewal.

Initial prior authorization: generally 6 months (see indication-specific exceptions).
Thymomas and thymic carcinomas: initial approval = six (6) cycles; prior authorization may NOT be renewed for these indications.
Mesothelioma combinations: initial approval = six (6) cycles with bevacizumab + platinum OR six (6) doses with pembrolizumab + platinum; renewals may NOT be permitted for these combinations.
Renewal: may be renewed every 6 months if renewal criteria met (see renewal criteria).

Note

Prior Authorization Considered for Cost

Prior authorization was considered appropriate in part because of the drug cost. Utilization management (including PA) was applied consistently with non-quantitative treatment limitation (NQTL) considerations.

Appendix conclusion: Cost of drug = Yes: Consider for PA.
Utilization management NQTL applied comparably across benefits (MH/SUD and M/S).

Denial Risk

Diagnosis-Driven Coverage and Diagnosis Code Matching

Coverage determinations are diagnosis- and indication-driven. Claims must include a listed covered ICD-10 diagnosis code that matches an approved indication; claims without a listed covered diagnosis code risk denial.

Provider must submit an ICD-10 diagnosis code from the covered-diagnosis list (Appendix 1).
Claims lacking a listed covered ICD-10 diagnosis code may be denied.
Non-Medicare determinations follow the listed diagnosis codes and indication-specific criteria.

Note

Medicare Policy Compliance

For Medicare members, follow applicable CMS rules. Medicare (Part B) claims must comply with the Medicare Benefit Policy Manual and any relevant NCDs, LCDs, or LCAs; consult the CMS coverage database for applicable determinations.

Medicare coverage guidance supersedes non‑Medicare policy where applicable.
Search for NCD/LCD/LCA at: https://www.cms.gov/medicare-coveragedatabase/search.aspx before adjudicating Medicare claims.

Denial Risk

Toxicity and Duration Risks (Denial/Renewal Considerations)

Authorization may be denied or not renewed for unacceptable toxicity or if the maximum duration for the indication has been exceeded. Examples of unacceptable toxicity include significant myelosuppression, renal toxicity (e.g., CrCl < 45 mL/min), severe dermatologic reactions, interstitial pneumonitis, and radiation recall.

Unacceptable toxicity examples: neutropenia, febrile neutropenia, thrombocytopenia, anemia, CrCl < 45 mL/min, Stevens-Johnson Syndrome/TEN, interstitial pneumonitis.
Prior authorization will not be renewed if toxicity is unacceptable or indication-specific duration limits have been reached.

Documentation Required

Required Clinical Documentation

Required clinical documentation must be provided at time of prior authorization request. Include diagnosis, indication-specific clinical notes, prior treatment history (including intolerance to or failure of prerequisite therapies when applicable), performance status, and relevant tumor biomarker or genomic testing when required by the indication.

Document patient age and performance status (e.g., KPS where applicable).
Provide prior therapy history, including intolerance to first-line combination regimens when use as single agent is requested.
When coverage depends on tumor biomarker status (e.g., EGFR, EGFR exon 20 insertion, BRAF V600E, NTRK, MET exon 14, NRG1, ERBB2/HER2, KRAS G12C), include FDA-approved or CLIA-compliant test results.
For CNS/PCNSL or leptomeningeal indications, include CSF cytology, neurologic status, and imaging as applicable.

Billing Rule

Coding and NDC Documentation

Billing must use the appropriate HCPCS J-codes and include the NDC and manufacturer designation for the specific product administered. Verify code/NDC combinations against the billing guidance in the policy's billing section.

Examples of HCPCS codes listed: J9322, J9297, J9296, J9294, J9304, J9314, J9323, J9292 (see billing section for full list).
Include the appropriate NDC associated with the administered product and manufacturer in claim documentation.
Ensure HCPCS code and NDC/manufacturer pairings match the product administered to avoid claim denials.

Step Therapy

Prerequisite Therapy Considerations

Prerequisite therapy considerations: when the policy specifies use as a single agent because the patient is unable to tolerate first-line combination regimens, documentation of intolerance or contraindication to first-line combination therapy is required.

If requesting single-agent use due to intolerance to combination therapy, include clinical documentation supporting intolerance or contraindication to first-line combination regimens.
Do not substitute prerequisite therapy requirements with unrelated treatments; prior therapy requirements must be met or documented as not tolerated when specified.

Line of Therapy — First-line, Subsequent, Second-line, Adjuvant

Line‑of‑Therapy Rules

First‑line: Indications where pemetrexed may be used as initial systemic therapy: peritoneal mesothelioma (adjuvant after CRS+HIPEC for high‑risk or first‑line if inoperable/incomplete cytoreduction), pleural mesothelioma (induction or first‑line for selected patients), non‑squamous NSCLC for tumors negative for actionable biomarkers or specified driver‑positive tumors when listed, thymic malignancies (preoperative if R0 uncertain; first‑line for recurrent/metastatic disease)

Subsequent: Indications for subsequent (later‑line) use: cervical, vaginal, ovarian/fallopian tube/primary peritoneal cancers as single‑agent subsequent therapy for recurrent/metastatic disease; pleural and peritoneal mesothelioma and NS‑NSCLC as subsequent therapy including rechallenge after prior pemetrexed response; thymic carcinoma second‑line for unresectable/metastatic disease

Second‑line: Indications specifically noted as second‑line: thymic malignancies (second‑line for unresectable/metastatic disease) and anaplastic thyroid carcinoma (second‑line for stage IVC); use in relapsed/refractory primary CNS lymphoma also applies

Adjuvant use after CRS+HIPEC for peritoneal mesothelioma patients with surgical/pathologic high‑risk features; postoperative use after R1/R2 resection for thymic carcinoma

Definitions and Key Terms

High-risk features for peritoneal mesothelioma

Ki-67 proliferation indexKi-67 > 9% is considered a high-risk feature

Nodal metastasisPresence of nodal metastasis qualifies as a high-risk feature

Peritoneal Cancer Index (PCI)PCI > 17 indicates high disease burden/incomplete cytoreduction and is a high-risk feature

Completeness of cytoreduction (CC) scoreCC score > 1 (incomplete cytoreduction) is a high-risk feature

Histology and extentBiphasic or sarcomatoid histology, thrombocytosis, PS = 2, or bicavitary disease are high-risk features

505(b)(2) designated product (Ψ)

Definition505(b)(2) designated products are those approved by FDA as 505(b)(2) NDAs of the innovator product

Therapeutic equivalenceThese products are not rated as therapeutically equivalent to the reference listed drug in the FDA Orange Book

Single-source statusMay be considered single‑source products under the statutory definition in section 1847A(c)(6) of the Act

Reference listsFor complete lists of approved 505(b)(2) products and NDCs, reference the FDA Orange Book and National Drug Code Directory

Covered Diagnosis Codes (definition)

ScopeICD-10 diagnosis codes correspond to covered malignant neoplasms, mesothelioma variants, peritoneal neoplasms, CNS secondary neoplasms, lymphomas, and related history/benign/uncertain behavior codes

Selected lung/thymus/mesothelioma codesC33, C34.00–C34.92, C37, C45.0–C45.9, C48.1, C48.2, C48.8

Peritoneum/mesothelioma codesC45.2, C45.7, C45.9, C48.1, C48.2, C48.8

Female genital and thyroid codesC52, C53.0–C53.9, C56.1–C56.9, C57.00–C57.9, C73

Secondary neoplasms and lymphomasC79.31, C79.32, C83.30, C83.390, C83.398, and related lymphoma codes; history codes Z85.118, Z85.238, Z85.43, Z85.850

CMS Coverage References

Medicare guidanceMedicare Part B coverage may be governed by the Medicare Benefit Policy Manual and by applicable NCDs, LCDs, and LCAs; compliance is required where applicable

Search resourceCMS Medicare Coverage Database may be used to search for NCD, LCD, or LCA documents (https://www.cms.gov/medicare-coveragedatabase/search.aspx)

Medicare Part B diagnosis codes listedMedicare Part B Covered Diagnosis Codes: N/A for this policy appendix (no specific Part B diagnosis codes listed)

MAC contractor notePalmetto GBA is listed as the MAC for multiple jurisdictions including the one covering NC

OpenPayer

Pemetrexed (Alimta, Pemrydi, Pemfexy) — Intravenous therapy coverage

Coverage Criteria for Pemetrexed (IV)

Coding: HCPCS, J-Codes, and Diagnosis Codes

Provider Actions, Prior Authorization, and Billing Requirements

Line of Therapy — First-line, Subsequent, Second-line, Adjuvant

Biomarker and Genomic Testing Requirements

Background and Clinical Context

Definitions and Key Terms

Policy Revision History