Association of tumor mutational burden in metastatic castration-resistant prostate cancer with response to checkpoint inhibition

Multiple studies of checkpoint inhibition (CPI) for metastatic castration-resistant prostate cancer (mCRPC) found little efficacy. In some studies, a small subsets of patients derived a benefit from CPI treatment. A retrospective study at City of Hope Comprehensive Cancer Center (Duarte, CA) investigated the association of tumor mutational burden (TMB) status of mCRPC and response to CPI therapy. The study included 23 evaluable mCRPC patients receiving pembrolizumab from 2014 to 2023. Ten patients were classified as TMB high and 13 were classified as TMB low/medium. The ORR was 50% in the TMB high group versus 0% in the TMB low/medium group. Two patients in the TMB high group achieved complete response. PSA response of 50% reduction were achieved in 50% of the TMB high group and 0% in the TMB low/medium group. TMB high was associated with median progression-free survival of 19.34 months versus 2.53 months with TMB low/medium (HR 0.08; p<0.001). The trend toward improved overall survival with TMB hogh versus TMB low/medium did not reach statistical significance (HR 0.37; p=0.08). The authors conclude that TMB high status may be a biomarker for favorable outcomes with CPI therapy for mCRPC.