Pembrolizumab

Pembrolizumab removes PD-1-mediated inhibitory signaling from T cells, enabling antitumor immune responses in selected cancers, but it can also trigger inflammation in almost any normal organ.

Pembrolizumab binds PD-1 on activated T cells and blocks its interaction with PD-L1 and PD-L2. Tumors can exploit this checkpoint to reduce T-cell activity; blocking it can restore immune recognition and killing. The effect depends on the tumor, immune microenvironment, prior treatment, and host factors. [P1, P2]

Because the mechanism activates immunity rather than directly targeting only tumor cells, adverse effects can reflect immune attack on healthy tissues. These immune-mediated reactions may occur during treatment or after the drug has been stopped. [P1]

The June 2026 U.S. label contains numerous disease- and setting-specific indications. The summary below groups them for readability; stage, treatment line, combination partner, age, and biomarker requirements differ within each group. The current label must be checked before publication or clinical use. [P1]

Melanoma: unresectable/metastatic disease and selected adjuvant settings. [P1, P2]

Thoracic cancers: NSCLC in several metastatic, perioperative, and adjuvant settings; and unresectable advanced or metastatic malignant pleural mesothelioma in combination with chemotherapy. [P1, P3]

Head and neck squamous cell carcinoma: recurrent/metastatic settings and, for PD-L1-positive resectable locally advanced disease, a neoadjuvant/adjuvant strategy. [P1]

Hematologic cancers: relapsed or refractory classical Hodgkin lymphoma and selected primary mediastinal large B-cell lymphoma. [P1]

Urothelial and bladder cancer: advanced disease, BCG-unresponsive high-risk non-muscle-invasive disease, and selected perioperative muscle-invasive bladder cancer in combination with enfortumab vedotin. [P1]

Biomarker-defined solid tumors: unresectable/metastatic MSI-H or dMMR tumors; MSI-H/dMMR colorectal cancer; and selected TMB-H solid tumors. [P1, P4]

Gastrointestinal cancers: selected gastric/GEJ, esophageal/GEJ, biliary tract, and hepatitis-B-related hepatocellular carcinoma settings. [P1]

Gynecologic cancers: selected cervical, endometrial, ovarian, fallopian-tube, and primary peritoneal cancer settings. [P1]

Renal cell carcinoma: first-line combinations and selected adjuvant treatment after surgery. [P1]

Skin cancers: recurrent/advanced Merkel cell carcinoma and cutaneous squamous cell carcinoma not curable by surgery or radiation. [P1]

Triple-negative breast cancer: high-risk early-stage perioperative treatment and selected PD-L1-positive unresectable or metastatic settings. [P1]

PD-L1 expression: reported as Tumor Proportion Score (TPS) or Combined Positive Score (CPS), depending on cancer type. The cutoff is indication-specific; a result cannot be transferred blindly from one tumor type to another. Assay platform, specimen age, tumor heterogeneity, treatment history, and the presence of immune cells can influence the result. [P1]

Mismatch repair and microsatellite instability: MSI-H or dMMR status can predict benefit in several tumor-agnostic and colorectal/endometrial indications. Testing may use immunohistochemistry for MMR proteins, PCR, or validated next-generation sequencing. An abnormal result can also suggest Lynch syndrome and may warrant germline genetic evaluation. [P1, P4]

Tumor mutational burden: for the U.S. tissue-agnostic TMB-H indication, the label uses a validated threshold of at least 10 mutations per megabase and an FDA-authorized test. TMB is assay-dependent and is not a universal predictor across all cancers. [P1]

When no biomarker is required: several labeled uses do not require PD-L1, MSI, or TMB positivity. Conversely, a positive PD-L1 result does not guarantee response, and a negative result does not always exclude benefit when the indication does not require it. [P1]

Keytruda is administered by intravenous infusion. A distinct U.S.-approved co-formulation, Keytruda Qlex (pembrolizumab and berahyaluronidase alfa-pmph), is administered subcutaneously and should not be represented as the same formulation or administration process. This document omits dose and schedule. [P1, P10]

Common effects with pembrolizumab monotherapy can include fatigue, musculoskeletal pain, decreased appetite, itching, diarrhea, nausea, rash, fever, cough, shortness of breath, constipation, and abdominal pain. In combination regimens, adverse effects also reflect chemotherapy, targeted therapy, antibody-drug conjugates, radiation, or other partners; therefore a single "common side-effect list" cannot accurately cover every indication. [P1]

The defining serious risk is immune-mediated inflammation. It may affect one or several organs, can be severe or fatal, and may begin after the last dose. Prompt recognition and guideline-directed immunosuppression are important. [P1]

Pneumonitis, especially important in people with prior thoracic radiation or lung disease. [P1]

Colitis and severe diarrhea; hepatitis; nephritis; pancreatitis; myocarditis; neurologic syndromes; severe skin reactions; and other uncommon organ toxicities. [P1]

Endocrine disorders, including thyroid dysfunction, hypophysitis, adrenal insufficiency, and type 1 diabetes; hormone replacement may be long-term. [P1]

Infusion-related reactions. [P1]

Complications before or after allogeneic hematopoietic stem-cell transplantation. [P1]

Embryo-fetal harm. [P1]

Increased mortality observed when PD-1/PD-L1 blockade was combined with a thalidomide analogue and dexamethasone in multiple myeloma outside controlled trials. [P1]

Baseline and periodic liver enzymes, creatinine, thyroid function, and clinical review for immune-mediated symptoms. [P1]

Glucose and endocrine evaluation when symptoms suggest diabetes, adrenal insufficiency, or pituitary disease. [P1]

Prompt imaging or specialist assessment for new respiratory, cardiac, neurologic, gastrointestinal, skin, or visual symptoms. [P1]

Treatment-partner-specific monitoring, such as blood counts, cardiac testing, or blood pressure, when pembrolizumab is used in combination. [P1]

Pembrolizumab is not primarily cleared through CYP metabolism, so classic small-molecule drug interactions are not the main concern. Clinically important issues include overlapping toxicities with combination partners, immunosuppressive therapy needed to manage adverse events, transplant timing, and use in people receiving chronic immune suppression. The complete regimen, not pembrolizumab in isolation, determines many interaction risks. [P1]

A biomarker's meaning is cancer- and indication-specific; PD-L1 CPS 1, CPS 10, TPS 1%, and TPS 50% are not interchangeable. [P1]

Immune-related toxicity can occur even in a person whose cancer does not respond. [P1]

People with autoimmune disease, organ transplants, interstitial lung disease, or chronic immunosuppression may require especially individualized risk assessment because many pivotal trials excluded or underrepresented them. [P1]

Some indications are accelerated approvals and may depend on confirmatory evidence; the label can change. [P1]

Keytruda, Keytruda Qlex, and combination regimens should be represented separately in a drug database. [P1, P10]

Primary or acquired resistance may involve lack of tumor antigens, defective antigen presentation such as B2M loss, impaired interferon signaling such as JAK pathway alterations, T-cell exclusion, alternative immune checkpoints, immunosuppressive myeloid cells, or clonal evolution. These mechanisms are biologically diverse and are not captured fully by PD-L1, MSI, or TMB alone. [P8]

No single routine resistance test reliably selects a universal next treatment after pembrolizumab. Repeat biopsy, molecular profiling, and clinical-trial evaluation may be useful in selected settings. [P8]

KEYNOTE-671 helped establish perioperative pembrolizumab plus chemotherapy for resectable NSCLC. [P3]

KEYNOTE-177 established first-line pembrolizumab as an important option for MSI-H/dMMR metastatic colorectal cancer. [P4]

The June 2026 U.S. label reflects a rapidly expanding set of combination and perioperative indications, including new ovarian, triple-negative breast, renal, head-and-neck, and bladder settings added or updated in 2025-2026. [P1, P9]

Research priorities include better predictors than PD-L1 alone, ctDNA-guided duration, rational combination therapy, treatment de-escalation, and prevention of severe immune toxicity. [P8]

Regulatory indications and safety language are summarized primarily from U.S. FDA prescribing information. Approval status, testing requirements, formulations, and recommended use may differ in other countries or change after this document is published.