What blood tests are recommended before initiating pembrolizumab (pembrolizumab) therapy in a patient with cancer?

Blood Tests Before Initiating Pembrolizumab

The primary "blood test" required before pembrolizumab is actually tissue-based biomarker testing (PD-L1, MSI/MMR, TMB, or molecular alterations), not traditional serum laboratory tests—though baseline organ function tests are standard practice for monitoring treatment-related toxicities.

Cancer-Specific Biomarker Testing Requirements

Non-Small Cell Lung Cancer (NSCLC)

• PD-L1 expression testing is mandatory using an FDA-approved immunohistochemistry assay on tumor tissue before initiating pembrolizumab, as eligibility depends on tumor proportion score (TPS) thresholds 1
• For first-line therapy, pembrolizumab requires TPS ≥50% with negative or unknown EGFR mutations, ALK rearrangements, and ROS1 rearrangements 1
• For subsequent therapy after platinum chemotherapy, pembrolizumab requires TPS ≥1% 1
• Molecular testing for EGFR mutations, ALK rearrangements, and ROS1 rearrangements must be completed before considering pembrolizumab, as patients with these alterations should receive targeted therapy first 1
• Blood-based assays for EGFR and ALK exist but are less sensitive than tissue assays 1

Triple-Negative Breast Cancer

• PD-L1 testing with the 22C3 companion assay is required for metastatic disease, with eligibility defined as Combined Positive Score (CPS) ≥10 1, 2
• The 22C3 assay calculates CPS as the number of PD-L1-staining tumor cells, lymphocytes, and macrophages divided by total viable tumor cells, multiplied by 100 1
• For early-stage TNBC receiving neoadjuvant pembrolizumab, PD-L1 testing is NOT required, as benefit is independent of PD-L1 status 3, 2
• Different PD-L1 assays are not interchangeable—the specific assay validated for each checkpoint inhibitor must be used 1, 2

Prostate Cancer and Other Solid Tumors

• MSI-H/dMMR testing is recommended for metastatic castration-resistant prostate cancer (mCRPC) to identify pembrolizumab candidates 1
• Tumor mutational burden (TMB) testing should be considered, with pembrolizumab approved for TMB-H (≥10 mutations/megabase) solid tumors after prior treatment 1
• For mCRPC specifically, germline and tumor testing for homologous recombination repair (HRR) gene mutations (BRCA1, BRCA2, ATM, PALB2, FANCA, RAD51D, CHEK2, CDK12) should be performed if not previously done 1
• If MSI-H or dMMR is identified, referral to genetic counseling is mandatory to assess for Lynch syndrome 1

All Cancer Types

• Patients with metastatic cancer who are candidates for checkpoint inhibitor therapy should undergo MSI-H/dMMR testing to determine eligibility for pembrolizumab or dostarlimab-gxly 1
• TMB testing should be performed to determine eligibility for pembrolizumab monotherapy in patients with unresectable or metastatic solid tumors 1

Standard Laboratory Monitoring (Not Eligibility Tests)

While the provided evidence focuses on biomarker testing rather than routine laboratory tests, standard oncology practice includes baseline organ function assessment:

• Liver function tests (AST, ALT, bilirubin) are important for monitoring, as grade 3/4 elevations are the most common laboratory adverse events with pembrolizumab 4
• Thyroid function testing should be considered at baseline, as hypothyroidism is the most common immune-mediated adverse event 1, 3
• Renal function and complete blood count are standard for chemotherapy combinations but not specifically required for pembrolizumab eligibility

Critical Implementation Points

Timing of Testing

• All biomarker testing should be completed before treatment initiation to determine eligibility and avoid delays 1, 5
• For NSCLC, every effort must be made to establish genetic alteration status before proceeding with PD-L1 testing 1
• If biopsy risk is high and genetic testing is not feasible, PD-L1 testing alone is appropriate 1

Common Pitfalls to Avoid

• Do not use different PD-L1 assays interchangeably—each checkpoint inhibitor has a specific companion diagnostic with different scoring systems 1, 2
• Do not assume blood-based TMB (bTMB) predicts response—a recent study showed baseline bTMB was not associated with efficacy of pembrolizumab plus chemotherapy in NSCLC 6
• Do not initiate pembrolizumab in metastatic breast cancer if disease recurred within 12 months of completing neoadjuvant/adjuvant chemotherapy—this is an exclusion criterion 2
• Do not skip molecular testing in NSCLC—patients with EGFR, ALK, or ROS1 alterations should receive targeted therapy before immunotherapy 1

Tissue Requirements

• At least one core biopsy is needed for immunohistochemistry, with additional cores for genomic analysis if comprehensive testing is planned 7
• For metastatic disease, rebiopsy of a metastatic site is recommended as biomarker status may differ from the primary tumor 1