Pembrolizumab is an anti-PD-1 antibody used in multiple cancers. The predictive biomarker that most reliably identifies patients likely to respond to anti-PD-1 therapy in solid tumours is:
- A KRAS mutation status
- B High serum LDH levels indicating rapid cell turnover
- C Tumour mutational burden (TMB) >10 mutations/megabase and/or mismatch repair deficiency (MMRd)/microsatellite instability-high (MSI-H) ✓
- D PD-L1 gene amplification on chromosomal 9p24
Explanation
Mismatch repair deficiency (MMRd) or microsatellite instability-high (MSI-H) is a pan-tumour predictive biomarker approved by the FDA for pembrolizumab use regardless of tumour origin — the first ever tissue-agnostic approval based on molecular biomarker. MMRd/MSI-H tumours accumulate large numbers of mutations (high TMB), generating abundant neoantigens that make them immunogenic and responsive to checkpoint blockade. Tumour mutational burden (TMB) >10 mutations/megabase is a broader criterion. PD-L1 expression (not gene amplification) is a partially predictive marker, but MMRd/MSI-H is more reliable. KRAS mutation predicts resistance to EGFR antibodies (cetuximab) in colorectal cancer, not immunotherapy response.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.