The information on this website is not intended for diagnosis or treatment. Please consult your physician for health concerns.

+90 850 321 50 00

MSI-H/dMMR Tumors and Pembrolizumab: Tissue-Agnostic Immunotherapy Approach

First tumor-agnostic FDA approval based on biomarker rather than tissue origin transforming oncology paradigm

Written by: Saygı Hospital Health Guide Editorial Board
Published:

This content is for general information; please consult your physician for diagnosis and treatment.

References (5)

This content is for informational purposes only and does not constitute medical advice. You can book an appointment at our Onkoloji department. Book Appointment →

What is MSI-H/dMMR Tumors and Pembrolizumab: Tissue-Agnostic Immunotherapy Approach?

Microsatellite instability-high reflects defective DNA mismatch repair causing accumulation of mutations particularly at repetitive microsatellite sequences.

Mismatch repair deficiency results from MLH1, MSH2, MSH6 or PMS2 protein loss with immunohistochemistry detecting absent expression.

MSI-H/dMMR tumors demonstrate exceptionally high mutation burden generating neoantigens that elicit T-cell mediated antitumor immunity.

Pembrolizumab tissue-agnostic approval represents first FDA approval based on biomarker rather than tumor histologic origin.

Lynch syndrome features germline mismatch repair gene mutations causing inherited cancer predisposition particularly to colorectal and endometrial cancers.

Symptoms

Clinical presentation depends on primary tumor site with MSI-H/dMMR found in colorectal, endometrial, gastric, urothelial and other cancers.
Immunotherapy response patterns including pseudoprogression, hyperprogression and durable responses guide imaging interpretation and clinical decisions.
Immune-related adverse events including colitis, pneumonitis, hepatitis, endocrinopathies and skin toxicity require recognition and management.
Lynch syndrome may present with cancer family history, young age at diagnosis, multiple primary tumors or characteristic tumor pathology features.
Universal MSI/MMR testing recommended for colorectal cancer, endometrial cancer and increasingly other tumor types enables identification.

Risk Factors

Lynch syndrome features autosomal dominant inheritance with 70-80% lifetime colorectal and 40-60% endometrial cancer risk.
MLH1 promoter methylation as alternative cause of MMR loss occurs in sporadic colorectal cancer particularly in older women.
Other tumors developing MSI-H/dMMR through somatic mutations or methylation lack hereditary implications.
Genetic counseling recommended for MSI-H/dMMR tumors with germline testing identifying Lynch syndrome and enabling cascade family screening.
Prior immune-related adverse events, autoimmune disease and corticosteroid dependency affect treatment safety and selection.

When to See a Doctor?

If you experience any of the following symptoms, seek medical attention promptly:

  • MSI-H/dMMR identified on tumor testing should prompt referral to medical oncology for immunotherapy treatment consideration.
  • Lynch syndrome diagnosis warrants comprehensive surveillance program with colonoscopy, endometrial sampling and discussion of risk reduction.
  • Immune-related adverse events during treatment require prompt recognition with most managed effectively with treatment modification.
  • Severe immune-related toxicities including colitis with severe diarrhea, pneumonitis or endocrinopathies require urgent oncology evaluation.
  • Family cancer history suggesting Lynch syndrome warrants genetic counseling referral with possible germline testing.

Treatment Methods

01
Pembrolizumab 200 mg IV every 3 weeks or 400 mg every 6 weeks demonstrates activity across MSI-H/dMMR solid tumors with durable responses.
02
Comprehensive immune-related adverse event monitoring including endocrine, hepatic, renal, dermatologic and gastrointestinal assessment supports safety.
03
Treatment continues for 2 years or until progression or unacceptable toxicity with some long-term responders achieving durable remissions.
04
Lynch syndrome management includes intensive cancer surveillance, risk-reducing surgery consideration and chemoprevention discussion.
05
Multidisciplinary care including medical oncology, genetic counseling, surveillance specialists and patient education supports comprehensive personalized therapy and family-based cancer prevention strategies.

Which Department to Visit?

You can visit our Onkoloji department for these complaints. Our specialist physicians will create the most suitable treatment plan for you.

Learn About Onkoloji Department

Let us help you

You can make an appointment with our specialists or contact us for your concerns.

Book AppointmentContact Us

Related Health Topics

Other articles from the same department you may want to explore.

Anaemia

Dahiliye (İç Hastalıkları)

Anaemia is a low haemoglobin level that reduces oxygen delivery, causing fatigue, pallor, and shortness of breath. It is not a disease itself but a sign of many underlying conditions. Most cases are correctable with appropriate diagnosis and treatment.

Iron Deficiency Anaemia

Dahiliye (İç Hastalıkları)

Iron deficiency anaemia develops when dietary intake, absorption, or losses create an iron shortfall, most often affecting women and children. Identifying the underlying cause is the core of management, alongside iron replacement.

Vitamin B12 Deficiency

Dahiliye (İç Hastalıkları)

Vitamin B12 deficiency can cause megaloblastic anaemia, neurological symptoms, and cognitive impairment. Early treatment with intramuscular or oral B12 largely prevents irreversible complications.

Hypertension (High Blood Pressure) Management

Dahiliye (İç Hastalıkları)

Hypertension is often called the silent killer because it progresses symptom-free for years and can damage the heart, brain, kidneys, and eyes. Regular monitoring, lifestyle change, and evidence-based drug therapy dramatically reduce cardiovascular risk.

Chronic Kidney Disease

Dahiliye (İç Hastalıkları)

Chronic kidney disease is one of the most common complications of chronic conditions such as diabetes and hypertension, and can be silent in its early stages.

Hepatitis B (HBV)

Dahiliye (İç Hastalıkları)

Hepatitis B is a DNA virus infection causing acute and chronic hepatitis with risk of cirrhosis and hepatocellular carcinoma; diagnosis integrates HBsAg, HBeAg, anti-HBc, and HBV DNA with management based on disease phase using nucleos(t)ide analogues (entecavir, tenofovir) and universal infant vaccination.

Hepatitis C (HCV)

Dahiliye (İç Hastalıkları)

Hepatitis C is an RNA virus causing chronic hepatitis that may progress to cirrhosis and hepatocellular carcinoma; modern direct-acting antiviral (DAA) pangenotypic regimens (sofosbuvir/velpatasvir, glecaprevir/pibrentasvir) achieve sustained virologic response over 95% in 8–12 weeks with universal adult screening and cure for nearly all patients.

Fatty Liver Disease

Dahiliye (İç Hastalıkları)

Non-alcoholic fatty liver disease (NAFLD) is closely related to obesity and metabolic syndrome and is largely reversible with early treatment.

Health Disclaimer: The information on this page is prepared for general informational purposes only. It does not replace medical diagnosis and treatment. Please consult your physician for your complaints. Saygı Hospital does not accept responsibility for actions taken based on the information on this page.