Clinical benefit of adding radiation for immune checkpoint inhibitor-refractory Merkel cell carcinoma: A 27-patient analysis.

Merkel cell carcinoma (MCC) recurs in 40% of patients, and 30% will require systemic therapy. Although PD-L1 immune checkpoint inhibitors (ICIs) have improved outcomes for advanced MCC, over half of patients do not experience long-term disease control. MCC is radiosensitive, and there is evidence that radiation therapy (RT) can promote antitumor immunity. We performed an analysis of 27 prospectively followed patients whose MCC progressed on ICI use and who then received RT while continuing ICI use. The median progression-free survival on ICI alone was 2.8 months. After disease progression, continuation of ICI, and addition of RT, these same patients had median progression-free survival of 5.1 months (P = .09). Patients with acquired ICI resistance had lower risk of progression than those with primary resistance (hazard ratio = 0.35, 95% confidence interval = 0.14-0.89, P = .02). Patients who received a single dose of RT (8 Gy; n = 13) had a risk of disease progression similar to those of patients who received multiple fractions (≥20 Gy, n = 14) (hazard ratio = 0.87, 95% confidence interval = 0.37-2.00, P = .73). RT to all disease sites (n = 10) was associated with longer post-RT progression-free survival versus RT to a subset of sites (5.3 vs 2.8 months). RT was well-tolerated without significant toxicity and is a clinically useful salvage option for ICI-refractory MCC.