pembrolizumab (Keytruda) coverage
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Defines medical benefit coverage, prior authorization, step therapy, and clinical criteria for pembrolizumab (Keytruda) for AlohaCare Medicaid and Medicare members. Applies to requests for therapy supplied under the medical benefit (HCPCS J9271).
No material clinical or coverage changes in this revision.
Indication-specific Coverage Criteria
Adrenocortical Carcinoma
Covered when ALL of the following are met
Triple-Negative Breast Cancer (TNBC) - metastatic or locally recurrent
Covered when ALL of the following are met
High-risk early-stage TNBC (neoadjuvant/adjuvant)
Covered when ALL of the following are met
Cervical Cancer (persistent, recurrent or metastatic) — combination
Covered when ALL of the following are met
Cervical Cancer (recurrent/metastatic) — monotherapy
Covered when ALL of the following are met
Anal Cancer
Covered when ALL of the following are met
Colorectal Cancer (dMMR/MSI-H)
Covered when ALL of the following are met
Prior chemotherapy details vary by subscenario as listed in policy.
Cutaneous Squamous Cell Carcinoma (cSCC)
Covered when ALL of the following are met
Endometrial Cancer
Covered when ALL of the following are met
Esophageal / Esophagogastric Junction and Gastric Adenocarcinoma
Covered when ALL of the following are met (indication-specific thresholds)
Lymphomas, Kaposi Sarcoma, Melanoma, Merkel Cell, and Other Indications
Covered when ALL listed, indication-specific criteria are met
Non-Small Cell Lung Cancer (NSCLC) and Other Solid Tumors
Covered when ALL listed, indication-specific criteria are met
Actionable markers must be absent.
Sarcomas and RCC
Covered when ALL listed criteria are met
Relapsed/Refractory Mycosis fungoides/Sezary syndrome
Covered when ALL of the following are met for relapsed/refractory Mycosis fungoides/Sezary syndrome:
Advanced RCC (clear cell) — first-line combination
Covered when ALL of the following are met for advanced Renal Cell Carcinoma (RCC) first-line:
RCC — adjuvant treatment
Covered when ALL of the following are met for RCC adjuvant therapy:
RCC — non-clear cell, single-agent for relapse or stage IV
Covered when ALL of the following are met for RCC non–clear cell histology:
ASPS in combination with axitinib
Covered when ALL of the following are met for alveolar soft part sarcoma (ASPS):
Soft Tissue Sarcoma — monotherapy
Covered when ALL of the following are met for unresectable, recurrent, advanced, or metastatic Soft Tissue Sarcoma:
dMMR/MSI-H solid tumors
Covered when ALL of the following are met for unresectable or metastatic solid tumors with dMMR/MSI-H:
High TMB solid tumors
Covered when ALL of the following are met for unresectable or metastatic solid tumors with high TMB:
Extranodal NK-T-cell lymphoma (post-asparaginase)
Covered when ALL of the following are met for relapsed or refractory extranodal NK-T-cell lymphoma:
Thymic Carcinoma
Covered when ALL of the following are met for unresectable or metastatic Thymic Carcinoma:
Urothelial carcinoma — combination with enfortumab vedotin
Covered when ALL of the following are met for locally advanced or metastatic Urothelial Carcinoma with enfortumab vedotin:
Urothelial carcinoma — monotherapy
Covered when ALL of the following are met for locally advanced or metastatic Urothelial Carcinoma as monotherapy:
High-risk non-muscle invasive bladder cancer (BCG-unresponsive)
Covered when ALL of the following are met for high-risk non-muscle invasive (T1, high grade Ta, and/or CIS) urothelial carcinoma of the bladder:
Adequate BCG defined per policy.
The pharmacy benefit for pembrolizumab (Keytruda) is excluded and requests should be submitted under the medical benefit for infusion/injection administration (HCPCS J9271). Authorization is required under the medical benefit; typical initial approval duration is 3 months with reauthorization/continuation up to 12 months per policy criteria.
There are no exclusions listed for pembrolizumab beyond the indication- and therapy-specific coverage criteria and general contraindications described elsewhere in the policy.
Use is not supported when the member has previously received another anti-PD-1 or anti-PD-L1 agent for the same indication. Requests may also be denied if the member is receiving systemic immunosuppressive therapy for an autoimmune disease or chronic condition; the policy requires the member to be not receiving systemic immunosuppression across covered indications.
Initial Therapy and Entry Requirements
Initial therapy — Initial approval durations and requirement
Reauthorization and continuation rules
Initial approval duration: 3 months; reauthorization up to 12 months per policy.
Initial therapy requirements — Indication-specific initial therapy criteria
Indication-specific initial therapy criteria
Initial approval typically 3 months; Medicare Part B 90‑day transition may apply for new members.
Reauthorization and Ongoing Therapy
Continuation/Reauthorization
Reauthorization and continuation rules
What Providers Must Do / Watch For
Medical benefit prior authorization required for Keytruda
Authorization is required for Keytruda (pembrolizumab) when furnished under the medical benefit (HCPCS J9271). Initial approval is for 3 months; reauthorization/continuation may be granted up to 12 months if clinical benefit and ongoing compliance with the policy criteria are documented.
- HCPCS code: J9271 (Injection pembrolizumab 1 mg).
- Initial request duration: 3 months.
- Continuation/Reauthorization: up to 12 months per policy criteria.
Prior authorization required for anti‑PD‑1/PD‑L1 agents
Prior authorization is required for anti‑PD‑1/PD‑L1 agents and will be approved only when the indication‑specific coverage criteria are met (diagnosis, prior therapies, performance status, biomarker requirements, and absence of contraindications such as prior anti‑PD‑1/PD‑L1 therapy or systemic immunosuppression).
- Applies to listed agents including pembrolizumab and other anti‑PD‑1/PD‑L1 agents (see policy note).
- Approval requires meeting the per‑indication criteria (diagnosis, prior lines of therapy, ECOG/Karnofsky performance status, biomarker thresholds where specified).
- Requests are excluded if the member has received another anti‑PD‑1/PD‑L1 agent or is on systemic immunosuppressant therapy.
Medicare Part B 90‑day transition and step therapy
For new Medicare members a 90‑day Part B transition period applies during which active courses of treatment continue and Coverage and Step Therapy do not apply; after 90 days, Medicare Part B coverage and any step therapy requirements must be met.
- During the 90‑day transition, active courses (including out‑of‑network) are covered without meeting step therapy.
- After 90 days, Coverage and Step Therapy Criteria apply and must be met for continued coverage.
Document required combination or prior regimens
Some indications require prior or concurrent use of specific agents; include documentation of the required combination or prior regimens (for example, pembrolizumab must be used with axitinib or lenvatinib for certain RCC indications, and with enfortumab vedotin for a specified urothelial carcinoma indication).
- RCC first‑line requires combination with axitinib or lenvatinib (and Karnofsky ≥70%).
- Locally advanced/metastatic urothelial carcinoma combination indication requires use with enfortumab vedotin (J9177) and ineligibility for cisplatin.
Submit applicable Medicare LCD/NCD/LCA and clinical documentation
For Medicare Part B requests, review the applicable LCD/NCD/LCA for the Hawaii region; if no applicable LCD/NCD/LCA exists, submit documentation that the member meets the policy’s General Coverage Criteria including diagnosis, PD‑L1 or dMMR/MSI status where required, ECOG/Karnofsky performance status, prior therapies, and combination regimen details.
- Check CMS Medicare Coverage Database for current LCD/NCD/LCA for Hawaii.
- If no LCD/NCD/LCA applies, provide documentation meeting the policy’s General Coverage Criteria.
Provide molecular testing results or rationale
Document actionable molecular marker testing when relevant (EGFR, ALK, ROS1, BRAF, NTRK, MET, RET). If insufficient tissue precludes testing, document repeat biopsy/plasma testing attempts or rationale for treating as lacking driver oncogenes per NCCN guidance.
- Actionable markers expected: EGFR, ALK, ROS1, BRAF, NTRK, MET, RET.
- If testing not feasible, provide documentation of attempts or rationale per NCCN guidance.
Prior anti‑PD‑1/PD‑L1 therapy or systemic immunosuppression may preclude approval
Requests may be denied if the member has previously received another anti‑PD‑1 or anti‑PD‑L1 agent, or is receiving systemic immunosuppressant therapy for an autoimmune disease or chronic condition; verify prior immunotherapy and current immunosuppressive medications before submission.
- Policy repeatedly requires that member has not received treatment with another anti‑PD‑1 or anti‑PD‑L1 agent for covered indications.
- Policy excludes members receiving therapy for autoimmune/chronic conditions that require systemic immunosuppressants.
Prior/concurrent anti‑PD‑1 therapy or immunosuppression triggers denial
A request may be denied when prior anti‑PD‑1/PD‑L1 therapy has been given for the same indication or when the member is concurrently receiving systemic immunosuppressant therapy; explicitly confirm absence of prior anti‑PD‑1/PD‑L1 exposure and absence of systemic immunosuppressants in the medical record.
- Per‑indication criteria include statements that the member has not received another anti‑PD‑1/PD‑L1 agent.
- Per‑indication criteria require the member is not receiving therapy for autoimmune disease or chronic condition requiring systemic immunosuppressant.
Billing Codes and Clinical Markers
| J9271 | Injection pembrolizumab 1 mg |
| J9177 | Enfortumab vedotin (Padcev) |
Step Therapy Considerations
| Medicare Part B step therapy | Notes |
|---|---|
| No formal Medicare Part B step therapy specified in this document | |
| For new starts, Medicare Part B step therapy criteria must be met in addition to Coverage Criteria before a request may be approved; a 90-day transition period for new members may apply (see Medicare Part B transition policy). |
| Step | Requirement | Supporting details |
|---|---|---|
| 1 | ||
| Use in combination with enfortumab vedotin (Padcev) for specified urothelial carcinoma indication | ||
| Covered when member has locally advanced or metastatic urothelial carcinoma and is using pembrolizumab in combination with enfortumab vedotin (J9177); member must be ineligible for cisplatin-containing chemotherapy, have ECOG 0-2, no prior anti-PD-1/PD-L1 therapy, and not be receiving systemic immunosuppressant therapy. |
| Step | Requirement | Effect on approval |
|---|---|---|
| 1 | ||
| Prior anti-PD-1/PD-L1 therapy | ||
| Prior treatment with another anti-PD-1 or anti-PD-L1 agent precludes approval for most listed indications; requests should document absence of prior anti-PD-1/PD-L1 therapy for approval consideration. |
Dosing and Quantity Limits
Place of Service / Benefit
Infusion center — medical benefit coverage; pharmacy excluded
Pembrolizumab is covered when furnished as an infusion/injection under the medical benefit; it is excluded from the pharmacy benefit and should be billed using the medical benefit (infusion center) setting.
- Formulary status: Medical Benefit — Authorization Required; Pharmacy Benefit: Excluded to Medical Benefit
- Site of care: infusion/injection under medical benefit
Key Definitions and Clinical Terms
Background
Pembrolizumab (Keytruda) is an anti–PD-1 monoclonal antibody used as monotherapy or in combination with other agents for a range of advanced, unresectable, recurrent, or metastatic malignancies. Coverage determinations in this policy incorporate tumor biomarkers (for example PD-L1 expression or dMMR/MSI-H status) where required, prior lines of therapy, and patient performance status (ECOG or Karnofsky) to determine eligibility for treatment.
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