Clinical activity of pembrolizumab in refractory MDM2 -amplified advanced intimal sarcomas.
Maurício Fernando Silva Almeida RibeiroElizabeth G DemiccoAlbiruni Ryan Abdul RazakPublished in: Therapeutic advances in medical oncology (2024)
Intimal sarcoma (InS) is an ultra-rare and aggressive subtype of soft tissue sarcoma (STS). It usually arises in large mediastinal arteries and the heart. In the advanced setting, sequential cytotoxic chemotherapy is often used, mainly based on retrospective studies and case series but with modest benefit. The use of immune checkpoint inhibitors is a promising strategy for some STS, but identifying biomarkers of response remains challenging due to disease rarity and heterogeneity. A reactive and pro-inflammatory tumor microenvironment (TME) is believed to be associated with better outcomes for patients receiving anti-PD-1-based regimens, generating the rationale to explore this strategy in malignancies with this characteristic, such as InS. We report three cases of advanced InS patients experiencing partial response to pembrolizumab-based therapy despite low tumor mutational burden and absence of mismatch-repair deficiency. We hypothesize that TME-related characteristics such as PD-L1 expression and the presence of tertiary lymphoid structures might explain this phenomenon.
Keyphrases
- end stage renal disease
- ejection fraction
- chronic kidney disease
- high resolution
- newly diagnosed
- advanced non small cell lung cancer
- heart failure
- clinical trial
- peritoneal dialysis
- lymph node
- cross sectional
- atrial fibrillation
- single cell
- stem cells
- high grade
- patient reported outcomes
- squamous cell carcinoma
- insulin resistance
- bone marrow
- locally advanced
- mass spectrometry
- tyrosine kinase
- rectal cancer
- epidermal growth factor receptor