Clinical approach and utilizing liquid biopsies to interrogate suspected acquired resistance to PD-1 blockade

Figures & data

Figure 1. Timeline of the patient.

At baseline, no targetable mutations, but liquid biopsy detected TP53, ARID1A, KEAP1 and SMARCA4 mutations. After complete response, at 14 months, a solitary pulmonary nodule was detected on CT, and it was PET avid indicative of potentially acquired resistance to PD-1 therapy. Liquid biopsy detected clearance and was inconsistent with radiology. Further investigation with tissue biopsy at 16 months revealed a benign diagnosis and refuted the progression of the disease.

Figure 2. Schema for investigation of acquired resistance to PD-1 blockade.

After CT diagnosis of the pulmonary nodule, proceed with functional imaging with a PET scan. If PET avid, proceed to liquid biopsy to confirm progression, identify therapeutic targets, and for consideration of management change. If the liquid biopsy confirms clearance, i.e., ongoing response, proceed to tissue biopsy to characterize the pulmonary nodule.