EmblemHealth pemetrexed coverage update

Coverage Criteria

Malignant Pleural Mesothelioma

Covered for malignant pleural mesothelioma when ONE of the following is met:

MPM regimens: Use in combination with cisplatin or carboplatin for stage I-IIIA clinically operable disease; OR in combination with pembrolizumab (Keytruda) and cisplatin/carboplatin as first-line treatment of unresectable advanced or metastatic disease; OR as first-line therapy for unresectable or metastatic disease as a single agent or in combination with cisplatin or carboplatin with or without bevacizumab; OR as subsequent single-agent therapy if not previously used in the first-line setting.

Non-Small Cell Lung Cancer (NSCLC)

Covered for recurrent or metastatic non-squamous NSCLC when ANY of the following are met:

NSCLC first-line: First-line therapy in combination with carboplatin or cisplatin; OR first-line in combination with carboplatin/cisplatin plus pembrolizumab (Keytruda) for EGFR-negative and ALK-negative disease; OR first-line in combination with amivantamab (Rybrevant) + carboplatin for EGFR exon 20 insertion mutations; OR first-line in combination with durvalumab (Imfinzi), tremelimumab (Imjudo) and platinum-based chemotherapy for up to 4 cycles in adult members with metastatic/Stage IV disease who are EGFR and ALK negative (may be followed by maintenance durvalumab +/- tremelimumab and optional histology-based pemetrexed).

NSCLC subsequent and maintenance: Subsequent therapy in combination with carboplatin or cisplatin; OR subsequent therapy in combination with amivantamab + carboplatin for select EGFR mutation contexts (exon 19 deletions or exon 21 L858R substitution mutations per policy); OR subsequent single-agent therapy; OR maintenance single-agent pemetrexed after response or stable disease following first-line chemotherapy; OR maintenance in combination with pembrolizumab following first-line pembrolizumab + pemetrexed + platinum; OR the regimen nivolumab + ipilimumab + carboplatin/cisplatin + pemetrexed followed by maintenance nivolumab + ipilimumab for PD-L1 ≥1% (note: specific regimens may be unsupported per policy due to lack of Level 1 evidence).

Exclusions include use where dosing would exceed the single-dose limit of 500 mg/m2; treatment when the member has documented disease progression on a pemetrexed-containing regimen; use for squamous cell NSCLC; and investigational or off-label uses that lack sufficient evidence or are not supported by CMS-recognized compendia or acceptable peer-reviewed literature. The policy defines sufficiency of evidence by whether published studies adequately represent the patient and regimen, report clinically meaningful outcomes (ASCO-recommended thresholds such as hazard ratio < 0.80 or survival benefit ≥ 3 months), and use appropriate study designs; anecdotal reports and abstracts without full peer-reviewed publications are not considered adequate.

Per Evolent policy, J9304 (Pemfexy) is not supported for the treatment of malignant pleural mesothelioma or non-small cell lung cancer when the product selection is justified solely on a claim of superiority; this recommendation is based on the lack of Level 1 evidence (randomized clinical trials and/or meta-analyses) demonstrating superior outcomes with one pemetrexed product over another.

Initial Therapy

Initial therapy covered when regimens match listed combinations:

MPM initial: Pemetrexed in combination with cisplatin or carboplatin for stage I-IIIA clinically operable malignant pleural mesothelioma; OR pemetrexed with pembrolizumab (Keytruda) plus cisplatin or carboplatin as first-line treatment for unresectable advanced or metastatic disease; OR pemetrexed as first-line single-agent or in combination with cisplatin or carboplatin with or without bevacizumab for unresectable/metastatic disease.

NSCLC initial: Pemetrexed in combination with carboplatin or cisplatin as first-line therapy; OR pemetrexed with carboplatin/cisplatin plus pembrolizumab for EGFR-negative and ALK-negative disease; OR pemetrexed with amivantamab (Rybrevant) + carboplatin for EGFR exon 20 insertion mutations; OR pemetrexed in combination with durvalumab (Imfinzi) and tremelimumab (Imjudo) plus platinum-based chemotherapy per the POSEIDON-like regimen for up to 4 cycles (may be followed by maintenance durvalumab ± tremelimumab and optional histology-based pemetrexed).

Continuation Therapy

Continuation Therapy Exemption

Continuation requests are exempt from policy review when ALL of the following are met:

Continuation criteria: Member has not experienced disease progression on the requested medication; AND the requested medication was used within the last year without a lapse of more than 30 days of having an active authorization; AND additional medication(s) are not being added to the continuation request.

Provider Actions & Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for pemetrexed (Alimta/Pemfexy/Axtle/Pemrydi) requests processed by Evolent for covered lines of business.

Applicable lines of business: Commercial; Exchange/Marketplace; Medicaid.

Note

Continuation Exemption

Continuation (renewal) requests for a previously authorized pemetrexed regimen may be exempt from full prior authorization review when all of the following are met: the member has not experienced disease progression while on the requested medication; the requested medication was used within the last year with no lapse of >30 days from an active authorization; and no additional medications are being added to the continuation request.

Coding and Billing

Pemetrexed HCPCS CodesHCPCS

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

Single-dose limit

Single-dose limit500 mg/m2

Applies toAlimta, Pemfexy, Axtle, Pemrydi (pemetrexed formulations)

Denial triggerRequests exceeding this single-dose limit are excluded from coverage

Context locationSee Exclusion Criteria for dosing limits and investigational/off-label guidance

Billing Rule

J9304 (Pemfexy) not supported for some indications

Step Therapy / Preferred Regimens

Regimen / Pathway	Coverage stance	Notes for prescribers
Pemetrexed in combination with carboplatin or cisplatin (first‑line or subsequent)	Covered when used as part of first‑line or subsequent platinum‑based regimens as specified in the NSCLC and MPM criteria.	Ensure diagnosis and line of therapy meet policy criteria; document planned folic acid and vitamin B12 supplementation and absence of contraindications.
Pemetrexed + pembrolizumab + carboplatin/cisplatin (first‑line for eligible NSCLC or allowed in MPM per updated indications)	Covered for EGFR‑/ALK‑ recurrent or metastatic non‑squamous NSCLC when used first‑line with pembrolizumab; added to MPM options where supported by evidence per policy history.	Provide molecular testing results (EGFR/ALK) and rationale for combination; cite FDA labeling or NCCN/ASCO guidance in request.
Pemetrexed + amivantamab (Rybrevant) + carboplatin (selected EGFR mutation contexts)	Covered in first‑line for EGFR exon 20 insertion mutations and as subsequent therapy for select EGFR exon 19 or exon 21 mutations per criteria.	Include mutation documentation (e.g., exon 20 insertion, exon 19 deletion, or exon 21 L858R) and prior EGFR TKI therapy history when applicable.
Pemetrexed + durvalumab + tremelimumab + platinum (POSEIDON‑style; up to 4 cycles) with optional histology‑based pemetrexed maintenance	Covered as first‑line for metastatic/Stage IV NSCLC negative for EGFR and ALK; may be followed by maintenance durvalumab with optional pemetrexed.	Document EGFR/ALK negative status and plan for maintenance therapy; reference POSEIDON‑style regimen per policy history update.
Bevacizumab + carboplatin/cisplatin + pemetrexed followed by maintenance bevacizumab + pemetrexed	Regimen specifically noted as not supported due to lack of Level 1 evidence showing superiority over Evolent‑recommended alternatives.	If submitting this regimen, provide high‑level randomized evidence demonstrating superior outcomes vs recommended alternatives; otherwise expect denial per policy.

Site of Care

Note

Medications processed and authorized by Evolent

All pemetrexed medication requests are processed by Evolent and require prior authorization; the policy notes medications are processed by Evolent (site-of-care specifics not detailed) and must be authorized before administration.

Evolent is responsible for processing medication requests
Authorization is required prior to reimbursement/administration

Background

Pemetrexed is an antifolate chemotherapeutic agent indicated for malignant pleural mesothelioma and non-squamous non–small cell lung cancer (NSCLC). It may be used as a single agent or in combination with platinum agents (cisplatin or carboplatin) and in select regimens with immunotherapy (for example, pembrolizumab in mesothelioma or pembrolizumab/durvalumab-containing regimens in NSCLC). Clinically important safety considerations include severe hypersensitivity and bone marrow suppression; routine prophylactic supplementation with folic acid and vitamin B12 is required to reduce hematologic toxicity. The policy specifies a single-dose limit of 500 mg/m2 and lists contraindication for severe hypersensitivity to pemetrexed or any component of the formulation.

Definitions

Myelosuppression

DefinitionMyelosuppression: severe bone marrow suppression that may include anemia, neutropenia, thrombocytopenia, and/or pancytopenia

Risk mitigationProphylactic folic acid and vitamin B12 supplementation are necessary to reduce hematologic toxicity, febrile neutropenia, and infection

Clinical consequenceSevere myelosuppression is often dose-limiting and may require blood transfusion or lead to neutropenic infection

Increased riskRisk for myelosuppression is higher in patients who did not receive vitamin supplementation

Product Notes & Formulations