Immunogenomic Analysis of Exceptional Responder to ALT-803 (IL-15 Analogue) in BCG Unresponsive Nonmuscle Invasive Bladder Cancer: A Case Series and Review of the Literature. Issue 9 (November 2019)

• Record Type: Journal Article
• Authors: Huang, Jeffrey; Shiao, Stephen L.; Furuya, Hideki; Rosser, Charles J.
• Is Part Of: Journal of immunotherapy. Volume 42:Issue 9(2019:Nov./Dec.)
• Publication Date: 2019-11
• Subjects: bladder cancer -- interleukin-15 -- biomarker -- therapy; Immunotherapy -- Periodicals; Immunotherapy -- Periodicals; Neoplasms -- therapy -- Periodicals; Electronic journals; Electronic journals; 615.37
• DOI: 10.1097/CJI.0000000000000269
• Languages: English
• ISSNs: 1524-9557

Abstract

Abstract : The clinical validity and utility of complex biomarkers have not been extensively studied in bladder cancer. Three patients with nonmuscle invasive bladder cancer [1 patient with an exceptional response; complete response (CR) for 30 months] who failed intravesical BCG were evaluated using an NYS CLEP approved assay, Immune Report Card, which measures programmed death-ligand 1 expression, CD8 + T-cell infiltration pattern, mutational burden, and gene expression of 51 immune-related transcripts using RNA-Seq. Patients were tested before being treated under our expanded access protocol for intravesical BCG with ALT-803. Subject 1 had failed his fourth line of therapy, subject 2 had failed only his first line of therapy, and subject 3 had failed his seventh line of therapy. Surprisingly, subject 1 had an unusually prolonged CR which lasted 30 months; subject 2 had the persistent and recurrent disease until 12 months when he then developed a CR; subject 3 had disease recurrence at 3 months, along with progression noted at 6 months. Immunomutational status was extensively evaluated to identify potential alterations that might play a role as predictive markers for subject 1, who had an exceptional response. Compared with subject 3, tumor in subject 1 demonstrated a high level of expression for CTLA4 (immunosuppression) and CD39 (immunosuppressive). Together, an immunosuppressive tumor environment in nonmuscle invasive bladder cancer that have failed prior BCG may respond better to interleukin-15 immunotherapy compared with tumors without an immunosuppressive environment. Abstract : Supplemental Digital Content is available in the text.