Abstract 1037P
Background
TMB predicts response to PD-1 immunotherapy (IO). High HLA class I diversity correlates with better responses in NSCLC. Standard to determine TMB and HLA diversity, is WES. We describe the correlation between TMB and HLA-diversity score by targeted NGS (TSO500) and outcome in immunotherapy treated NSCLC.
Methods
IO treated NSCLC patients (from 2016 to 2018) of who DNA was available after routine testing, were selected. 126 patient samples were analyzed by TSO500. TMB high is 10 mutations/Mb or more. HLA diversity is calculated as percentile of their score in the distribution of all pairwise class I allele scores. High HLA diversity is defined as diversity in at least one locus, in the upper 20th percentile. Clinical outcome parameters were collected (RR, DCR and DOR).
Results
Of 126 patients, 55 (44%) are TMB high and 71 (56%) low. High HLA diversity was noted in 57 (45%) and low HLA diversity in 69 (55%) patients. TMB high patients show higher RR than low patients [27 of 55( 49%) versus 18 of 71 (25%); p = 0.0084], but no significant difference in DCR [33 of 55 (60%) versus 30 of 71 (44%); p = 0.0755]. High HLA diversity shows no significant difference with low HLA diversity in RR [23 of 57 (40%) versus 22 of 69 (32%); p = 0.3545] nor in DCR [33 of 57 (58%) versus 31 of 69 (45%); p = 0.1473]. Combined high TMB and HLA diversity showed higher RR compared to low TMB and HLA diversity [13 of 23(57%) versus 8 of 37( 22%); p = 0.0113] as well as higher DCR [15 of 23 (65%) versus 13 of 37 (35%); p = 0.0232]. Triple positive patients (PD-L1 positive and high TMB and HLA diversity) showed a RR of 62% (8 of 13). Triple negative patients (PD-L1 negative, low TMB and HLA diversity) showed no (0 of 8) [p = 0.0068]. Median DOR was significant longer in triple positive compared to triple negative group (14 versus 3 months; p = 0.0459).
Conclusions
NSCLC patients with high TMB by TSO500, show higher RR to immunotherapy. HLA diversity score alone could not predict response, however combined high TMB and HLA diversity score show higher RR and DCR. Combined TMB, HLA diversity and PD-L1 can identify NSCLC patients likely to respond to or unlikely to benefit from IO. Hence TMB and HLA diversity score should be considered part of comprehensive genomic profiling.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Kristof Cuppens.
Funding
Has not received any funding.
Disclosure
S. Zhang, B. Zhang: Full/Part-time employment: Illumina Inc. All other authors have declared no conflicts of interest.