Pembrolizumab

• Non-Small Cell Lung Cancer
• Melanoma
• Head and Neck Cancer
• Hodgkin Lymphoma
• MSI-H Cancers

Pembrolizumab, marketed as Keytruda, is a humanized IgG4 monoclonal antibody targeting the programmed cell death protein 1 (PD-1) receptor on T cells. It is one of the most widely used immune checkpoint inhibitors in oncology, with FDA approvals across more than 18 tumor types and several tissue-agnostic indications based on biomarkers such as MSI-H/dMMR or high tumor mutational burden. Although it is administered and primarily monitored by oncology, primary care plays a critical role in recognizing the unique immune-related adverse events that can affect virtually any organ system, in supporting routine cancer-related health maintenance, and in coordinating chronic disease management during what is often multi-year treatment.

Mechanism of Action

PD-1 is an inhibitory checkpoint receptor expressed on activated T cells, B cells, and natural killer cells. When tumor or stromal cells display its ligands (PD-L1 and PD-L2), engagement transmits an inhibitory signal that dampens T-cell activation, proliferation, and cytotoxic function — a mechanism tumors exploit to escape immune surveillance. Pembrolizumab binds PD-1 with high affinity, blocking both PD-L1 and PD-L2 interactions and effectively releasing the brake on antitumor T-cell responses. The result is reactivation of cytotoxic T cells that can recognize tumor neoantigens and produce durable, sometimes years-long remissions even after treatment is discontinued. Because the immune system itself is reactivated, the same off-target activity that produces durable remission also produces immune-mediated adverse events that can resemble autoimmune disease — pneumonitis, colitis, hepatitis, endocrinopathies, dermatitis, nephritis, and rare but life-threatening myocarditis or neurologic syndromes. Tumors with high mutational burden, MSI-H/dMMR status, or PD-L1 expression generally respond more robustly, though responses occur even in PD-L1 negative tumors. The National Cancer Institute provides accessible patient information.

Clinical Use

Indications include melanoma (adjuvant after resection of high-risk disease and metastatic), non-small cell lung-cancer (multiple lines and combinations including with chemotherapy), classical Hodgkin and primary mediastinal B-cell lymphoma, urothelial, head and neck squamous cell, gastric/GEJ, esophageal, cervical, hepatocellular, renal cell, endometrial, triple-negative breast, Merkel cell, cutaneous squamous cell, and any unresectable or metastatic solid tumor that is MSI-H/dMMR or has high tumor mutational burden. Treatment is selected and managed by oncology, often with companion biomarkers (PD-L1 expression by combined positive score, MSI status, TMB) directing therapy. Pembrolizumab may be combined with chemotherapy, targeted agents, anti-angiogenic drugs, or other immune checkpoint inhibitors depending on the indication and stage. The ASCO clinical practice guidelines, NCCN frameworks, and tumor-specific consensus statements define standard of care. Primary care should ensure age-appropriate cancer screening continues for second primaries, coordinate vaccinations on a timeline that respects infusion schedules, manage cardiovascular risk factors aggressively (cancer survivors carry elevated cardiovascular mortality), and address bone health, nutrition, and mental health support.

How to Take It

Pembrolizumab is given by intravenous infusion in an oncology infusion center, typically 200 mg every three weeks or 400 mg every six weeks, over 30 minutes. Infusions continue until disease progression, unacceptable toxicity, or up to 24 months in patients without progression — adjuvant settings have defined durations (12 months for melanoma, for example). There is no oral self-administered component. Premedication is generally not required, although patients with a history of mild infusion reactions may receive acetaminophen or an antihistamine. Routine vaccination should be timed away from infusions when possible — inactivated vaccines including annual influenza and updated COVID-19 boosters are recommended and safe; live vaccines should be avoided during therapy and for several months afterward. Bring a current medication list including supplements to every infusion visit; herbal immunostimulants and high-dose antioxidants should be discontinued because of theoretical and emerging concerns about altered checkpoint inhibitor efficacy. Maintain hydration, balanced nutrition, and gentle physical activity as tolerated.

Monitoring and Follow-Up

Before each cycle, oncology obtains a CBC with differential, comprehensive metabolic panel including liver enzymes and creatinine, TSH, and free T4. Glucose and morning cortisol may be added periodically to detect endocrinopathies (type 1 diabetes, adrenal insufficiency, hypophysitis). A baseline ECG is reasonable; troponin and BNP are checked if myocarditis is suspected — even subclinical troponin elevation warrants urgent cardiology evaluation given the high mortality of immune-related myocarditis. Pulmonary function and chest imaging are pursued for any new dyspnea, hypoxia, or cough — pneumonitis can be subtle and rapidly progressive and is a leading cause of treatment-related mortality. Skin and stool changes are reviewed at each visit. Our understanding-blood-work-lab-panels primer can help patients understand which trends matter. Imaging response is typically assessed every 9–12 weeks per RECIST or iRECIST criteria, the latter accounting for pseudoprogression that can occur with immunotherapy. Long-term survivors require lifelong screening for delayed endocrinopathies, even years after treatment.

Special Populations

Patients with active autoimmune disease — including ulcerative colitis, Crohn disease, psoriasis with significant systemic involvement, lupus, multiple sclerosis, type 1 diabetes, and others — may be more prone to severe immune-mediated events; the decision to treat is individualized and shared with rheumatology, gastroenterology, or other specialists. Solid organ transplant recipients face a high risk of allograft rejection, and bone marrow transplant recipients may develop graft-versus-host disease. Pregnancy must be avoided; pembrolizumab can cause fetal harm based on mechanism (PD-1 blockade disrupts maternal-fetal tolerance), and effective contraception should continue for four months after the last dose. Breastfeeding should be discontinued during therapy and for four months after. No dose adjustment is required for renal impairment or for mild hepatic impairment; data are limited for moderate-to-severe hepatic dysfunction. Older adults are not at increased toxicity risk per pooled analyses but may have less physiologic reserve to manage severe events.

Drug Interactions and Practical Counseling

No formal cytochrome P450-based interactions exist because pembrolizumab is a protein cleared by reticuloendothelial catabolism. The clinically important interactions are pharmacodynamic. Systemic corticosteroids in immunosuppressive doses may blunt antitumor efficacy and should be avoided immediately before and during the early phase of treatment unless required for an immune-related adverse event, in which case rapid taper is the goal. Other immunosuppressants — calcineurin inhibitors, antimetabolites, biologics like adalimumab or infliximab — similarly counter the drug's mechanism. Live vaccines should be avoided during therapy and for several months afterward; inactivated influenza, COVID-19, pneumococcal, shingles (recombinant), and tetanus vaccines are appropriate and important. Antibiotics in the weeks before initiation may reduce checkpoint inhibitor efficacy through gut microbiome disruption, though the data are evolving. Probiotics and high-dose antioxidant supplements should generally be avoided. Patients should not start herbal immunostimulants such as echinacea, astragalus, or high-dose vitamin C without oncology approval.

Survivorship and Long-Term Considerations

Many patients now live years on or after pembrolizumab, and survivorship care is a growing primary care priority. Endocrinopathies including hypothyroidism, hypopituitarism, and adrenal insufficiency may emerge or persist; lifelong hormone replacement is sometimes required. Cardiovascular risk reduction — blood pressure, cholesterol, diabetes management, smoking cessation — preserves the survival gains from cancer treatment. Bone health screening, age-appropriate cancer screening for second primaries, sexual health, mental health (anxiety and depression are common in cancer survivors), and nutritional optimization all warrant ongoing attention. Coordination with oncology, endocrinology, cardiology, and other specialists is the norm rather than the exception. Our cancer-screenings-by-age overview supports patients in maintaining a complete preventive plan alongside their cancer therapy.

When to Contact Your Doctor

Report any new shortness of breath or persistent cough (pneumonitis), more than 2–3 watery stools above baseline or rectal bleeding (colitis), yellowing of skin or eyes, severe abdominal pain, severe fatigue or unexplained weight loss (endocrinopathy), severe headache or visual change, decreased urine output, chest pain or palpitations, severe muscle weakness, and skin rash or blistering. Symptoms should never be self-managed — early corticosteroids dramatically alter outcomes and delays can be fatal. Bring a wallet card identifying you as a checkpoint inhibitor patient to any emergency visit so that providers know to consider immune-related adverse events and avoid prematurely attributing symptoms to other causes.

Primary care and oncology partner closely on patients receiving immunotherapy. If you are on or considering pembrolizumab, contact us or schedule a visit so we can coordinate monitoring, vaccinations, chronic disease management, and survivorship care with your cancer team.