PDL1 landscape in checkpoint inhibitor ineligible patients by IHC and cfRNA.

Abstract

e14570 Background: Immune checkpoint inhibitors (ICT) are indicated in patients with PDL1+ IHC and restricted to certain histologies . Other tumor histologies express PDL1 at various frequencies with no established threshold for therapeutic efficacy. We evaluated traditionally ICT non-indicated histologies by IHC and cfRNA to determine potential therapeutic thresholds. Methods: A total of 97 pts (cancer of unknown primary [N = 10], appendix [N = 6], bile duct [N = 4], colorectal cancer [N = 25], esophageal [N = 6], ovary [N = 7], pancreas [N = 15], other [N = 24]) with IHC (Dako 76 22C3, 21 SP142) and cfRNA for PDL1 were available for analysis. cfRNA was a random draw not matched with the time of tissue collection and performed by qPCR. A cutoff of > 1.5x for PDL1 normalized to beta actin was defined as PDL1+ in cfRNA. IHC > 10% was used as the threshold for IHC+. Results: Most patients were PDL1- by IHC: 90/97 (93%), PDL1 TPS: 0% (N = 72), 1% (N = 7), 5% (N = 8), 10% (N = 3), > 10% (N = 3), > 50% (N = 4). No difference was seen between 22C3 and SP142 antibodies. PDL1+ cfRNA (N = 59), PDL1- cfRNA (N = 38). Positive concordance for cfRNA PDL1+ and IHC PDL1+ was 10.2% (6/59). Negative concordance for cfRNA PDL1 - and IHC PDL1- was 97.4% (37/38) (p = 0.079). Conclusions: In ICIs ineligible patients a > 50% IHC threshold is rarely met (4%). Random draw qPCR PDL1 is poorly correlated with IHC, with higher rates of PDL1+ in cfRNA in setting of IHC PDL1-. In the other hand, cfRNA PDL1- is strongly associated with an IHC negative result. Further investigation incorporating both cfRNA and IHC result to predict the response from ICIs are warranted.