Introduction: High-grade treatment-emergent neuroendocrine prostate cancer (T-NEPC) is a rare subtype of prostate cancer with limited therapeutic options and poor prognosis.Understanding biomarkers that influence the efficacy of immune checkpoint inhibitors (IO) is vital to form a better therapeutic arsenal for these patients.Case Presentation: We describe an impressive response to IO combination immunotherapy with ipilimumab plus Party nivolumab (Ipi/nivo) in a patient with T-NEPC who had failed standard treatment approaches.The patient was showing signs of a rapid decline in quality of life despite his prostate-specific antigen levels remaining undetectable and had no previous response to standard therapies.
The results of the next-generation sequencing DNA analysis demonstrated the presence of intermediary tumor burden, an ATM mutation and a rare SF3B1 (G742D) mutation, and served as rational for IO therapy in this patient.Conclusions: This case highlights the genetic profile of tumor Washing Machine Power Module with a rare combination of ATM and SF3B1 mutations that could be further explored as biomarkers for IO therapy in T-NEPC and other tumor types.