What monitoring is required after treatment with pembrolizumab (programmed death receptor-1 (PD-1) inhibitor), gemcitabine (nucleoside analog), and cisplatin (platinum-based chemotherapy)?

Monitoring After Pembrolizumab, Gemcitabine, and Cisplatin Treatment

Patients who have completed treatment with pembrolizumab, gemcitabine, and cisplatin require clinical and laboratory evaluation every 3 months during the first year, then every 6 months thereafter, with vigilant surveillance for immune-related adverse events that can develop even months after treatment cessation. 1

Post-Treatment Surveillance Schedule

First Year After Treatment

• Clinical and biological evaluation every 3 months 1
• Oncologists must actively seek occurrence or worsening of any symptoms related to immune-mediated toxicities, as these can develop even after therapy cessation 1

After First Year

• Clinical and biological evaluation every 6 months 1
• Continue monitoring for delayed immune-related adverse events 1

Required Laboratory Tests

At each surveillance visit, obtain the following laboratory panel: 1

• Complete blood count (CBC) 1
• Renal function tests (creatinine with estimated GFR) 1
• Serum electrolytes (sodium, potassium, calcium, phosphorus) 1
• Glycemia (blood glucose) 1
• Coagulation studies 1
• Liver function tests (total bilirubin, AST, ALT, GGT, alkaline phosphatase) 1
• Thyroid-stimulating hormone (TSH) 1

Imaging Surveillance

No routine imaging is recommended in the absence of symptoms 1. This is a critical distinction—imaging should only be performed when clinically indicated by new or worsening symptoms, not as routine surveillance 1.

Critical Immune-Related Adverse Events to Monitor

Patients receiving pembrolizumab must be monitored very closely for immune-related adverse events throughout treatment and after completion 1. The most common immune-related toxicities include:

Respiratory System

• Pneumonitis is the most common immune-related adverse event (30% of reported cases) 2
• Monitor for new or worsening dyspnea, cough, or chest pain 1
• Any respiratory symptoms should prompt immediate chest imaging 1

Gastrointestinal System

• Colitis occurs in approximately 25% of patients 2
• Assess for changes in bowel habits, diarrhea, abdominal pain, or blood in stool 1

Endocrine System

• Endocrine toxicities affect approximately 24% of patients 2
• Monitor for hypothyroidism, hyperthyroidism, hypophysitis, adrenal insufficiency, and type 1 diabetes 3
• Check TSH at every visit; if abnormal, obtain free T4 1
• Consider morning cortisol and ACTH if symptoms of adrenal insufficiency develop 1

Dermatologic System

• Skin reactions occur in approximately 21% of patients 2
• Examine for new rashes, pruritus, or vitiligo 1

Other Organ Systems

• Hepatitis (monitor liver function tests) 1
• Nephritis (monitor renal function and proteinuria) 1
• Neurologic toxicities including neuropathy 1
• Rheumatologic conditions such as polymyalgia rheumatica 3

Critical Clinical Pearls

Multiple Toxicities Can Occur Simultaneously

Elderly patients are at particularly high risk for developing multiple immune-related adverse events concurrently 3. One case report documented a patient developing four separate autoimmune toxicities (type 1 diabetes, pneumonitis, hypothyroidism, and polymyalgia rheumatica) within a short timeframe 3.

Delayed Onset of Toxicities

Immune-related adverse events can develop at any time: during treatment, immediately after completion, or months after cessation 1. Dysimmune toxicities have been reported occurring even after therapy discontinuation, necessitating prolonged surveillance 1.

Severity of Adverse Events

Among reported immune-related adverse events, approximately 42% result in hospital admission, 22% require long-term treatment, and 13% lead to permanent treatment discontinuation 2. Additionally, treatment-related adverse events can be fatal, with approximately 2% of deaths attributed directly to pembrolizumab-related toxicity 4.

Differential Diagnosis Approach

When any new symptom occurs during or after treatment, consider three potential etiologies systematically: 1

1. Disease progression (most common cause of new symptoms) 1
2. Fortuitous events (such as infection or thrombosis) 1
3. Treatment-related immune toxicity 1

Oncologists should maintain a global, non-biased view and properly investigate each possibility rather than focusing predominantly on one etiology 1. Neglecting immune-related toxicities could be potentially fatal, but ignoring fortuitous events like infections may also be deleterious 1.

Management of Suspected Immune-Related Adverse Events

Any suspicious symptoms should lead to proper investigation 1. The specific workup depends on the organ system involved:

• Respiratory symptoms: Obtain chest CT with thin sections 1
• Gastrointestinal symptoms: Consider colonoscopy for persistent diarrhea or colitis 1
• Endocrine symptoms: Obtain comprehensive hormonal evaluation 1
• Hepatic dysfunction: Evaluate for viral hepatitis and autoimmune markers 1

Follow ESMO clinical practice guidelines for management of toxicities from immunotherapy when immune-related adverse events are identified 1.

Special Considerations for Combination Therapy

The combination of pembrolizumab with gemcitabine and cisplatin does not introduce new safety signals beyond those expected from each agent individually 4. However, the cumulative toxicity profile includes:

• Myelosuppression from chemotherapy (neutropenia, thrombocytopenia) 5
• Nephrotoxicity from cisplatin 1
• Immune-related adverse events from pembrolizumab 1

Treatment-related adverse events with maximum grade 3-4 occur in approximately 70-79% of patients receiving this combination 4, emphasizing the importance of vigilant monitoring.