Fraction of copy-number alterations significantly predicts survival following immunotherapy in a few cancers

Abstract

Various studies have shown that high tumor mutation burden (TMB) may predict response to immune checkpoint therapy, at least in some cancer types 1,2. However, identifying patients with low TMB that are still likely to respond to cancer immunotherapy is an important open challenge. Recently, Spurr et al. 3 reported that the tumor aneuploidy score (AS), defined as the fraction of chromosome arms with arm-level copy number alterations in a sample, is predictive of survival following immunotherapy in low-TMB patients across multiple cancers. By re-analyzing the same data set by performing survival analysis in individual cancer types separately, we find that AS only significantly predicts survival in one single cancer indication. We further find that another metric conceptually related to the AS, the fraction of genome encompassed by copy number alterations (FGA), if called with a conventional copy number calling cutoff, has stronger predictive power than the AS proposed in 3, and that this observation holds even if the FGA and AS thresholds for presence/absence of copy number events are set comparably. However, with the current available data, even FGA can predict survival following immunotherapy in only a few cancer indications.