Supplementary Material for: A complete response to combined immunotherapy in a patient with an ATM plus SF3B1 mutation and a moderate tumor mutational burden with a high-grade treatment-emergent neuroendocrine prostate cancer (T-NEPC): Case report and review of the literature

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 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 (PSA) levels remaining undetectable and had no previous response to standard therapies. The results of the next sequencing generation (NGS) 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 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.