Correlation between tumor mutation burden and response to immunotherapy

• Published in: Journal of clinical oncology Vol. 35; no. 15_suppl; p. e14579
• Main Authors: Bonta, Ioana, Isac, John Florin, Meiri, Eyal, Bonta, Dacian, Rich, Patricia
• Format: Journal Article
• Language: English
• Published: 20.05.2017
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2017.35.15_suppl.e14579

Abstract only e14579 Background: The use of immunotherapy is exponentially increasing in treatment of patients with advanced solid tumors. However, the response rates vary significantly between different tumor types and even within same tumor type (e.g. in lung cancer approx. 1 in 4 patients respond to immunotherapy). In order to better identify patients that will respond to immunotherapy, several markers have been proposed. Tumor mutation burden (TMB) has emerged more recently as a quantitative marker that can help predict responses to immunotherapies across different cancers, including melanoma, lung cancer and bladder cancer. TMB is a measure of the overall number of somatic protein coding mutations occurring in the tumor specimen. Methods: We analyzed 54 consecutive patients treated with immunotherapy at our institution for which we had genomic sequencing (FoundationOne). There were 39 lung cases and 15 non-lung (GI, GU, sarcoma). For 30 cases we had TMB data. Favorable response was defined as stable disease or response to therapy at 3 months. The relationship between TMB and tumor response was explored using ROC analysis. Results: The probability of a favorable response to immunotherapy in our patient dataset was 57% (31/54 patients). Among the patients with known TMB 60% (18/30) had a favorable response (stable disease or response to therapy). The favorable response rate for tumors originating in the lung was 64% (25/39) and for non-lung primary tumors was 40% (6/15). The difference was not statistically significant, with p = 0.12. Higher TMB values were correlated with increased probability of a favorable response. ROC analysis demonstrated an A z of 74% for TMB values in differentiating between patients with and without a favorable response. A TMB cutoff value of 8 mutations/megabase yielded a sensitivity of 95% and a specificity of 58% for predicting favorable response. Conclusions: In our data base 57%of patients with different solid cancers had favorable response to immunotherapy, in second line and beyond .Higher TMB correlated with higher likelihood of response to immunotherapy, independent of the primary site of cancer.