Immunotherapy Efficacy in SMARC-Altered Cancers: A pan-cancer analysis of clinical outcomes in response to immune checkpoint inhibition

The switch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complex and its SMARC subunits regulate gene expression. Altered SMARC is rare yet may enhance immunotherapy response. In this retrospective analysis of metastatic SMARC-altered solid tumors in the University of California San Diego (UCSD) medical record (6,831 patients), 53 patients with diverse SMARC-altered malignancies were evaluable. Outcomes were compared between patients receiving immune checkpoint inhibitors (ICIs; n = 28, median second line) and those never treated with ICIs who received first-line, non-immune systemic therapy ( n = 25). ICI-treated patients had a higher objective response rate (ORR, 48% vs. 16%) and longer median progression-free survival (PFS, 10.6 vs. 5.8 months) and overall survival (OS, 21.8 vs. 10.7 months) ( p < 0.05). ICI treatment independently predicted longer OS (hazard ratio [HR] = 0.37, 95% confidence interval [CI]: 0.18–0.74, p = 0.005) and a higher ORR (OR = 4.88, 95% CI: 1.32–18.0, p = 0.02). SMARC-altered metastatic tumors derive superior ORR, PFS, and OS from ICI versus non-ICI therapies, despite ICIs being administered as later-line therapy. Prospective trials in SMARC-altered cancers are warranted.