DNA Report page 4
Figure 4 Circos plot of CNA and somatic mutations. From outermost to innermost track: progression sample CNA (log2R), baseline sample CNA (log2R), progression sample mutations and baseline sample mutations. CNAs, copy number alterations.
evidence suggests chemotherapy causes a degree of immune activation,9 and studies propose rational combination and sequencing of chemotherapy and CPI to achieve this end. The phase II DREAM study of durvalumab in combination with pemetrexed and cisplatin gave an objective treatment response rate of 48%, and a phase III is planned.10
The reduction in the number of somatic mutations between two samples can suggest subclones eliminated by pembrolizumab. This phenomenon is well described previously in patients with melanoma treated with nivolumab.11 On treatment with CPI, immunoediting
occurs where tumor cells expressing neoantigens targeted by activated T cells are lost.12 The resulting loss of cancer heterogeneity results in more homogenous cancer cell population and a lower rate of somatic mutations and a lower TMB.
the case in context as a long-term responder to pembrolizumab and chemotherapy
What is remarkable about this patient’s initial response is the depth and duration. The relapse of disease occurred 21 months after the last dose of pembrolizumab. A recent paper suggests nivolumab can be detected more
