ESH CLL 2022 | The impact of gene mutations on prognosis in CLL

So in the last 10, 15 years, there has been a dramatic increase in our knowledge of recurrent genetic aberrations that have been discovered in CLL. And it’s quite a heterogeneous pattern with just a handful that are more frequent and a very long tail of less recurrent gene mutations. And today, more than 25 different gene mutations have been shown to have prognostic impact in CLL. And what we have started to wonder is if these gene mutations have the same impact in IgHV-unmutated and IgHV-mutated CLL. So in order to test this, we collected a very large cohort of more than 4,500 patients where we sequenced nine recurrent genes in CLL and grouped patients into the IgHV-mutated subgroup that has better prognosis and IgHV-unmutated with a worse prognosis. And then we looked in each group what the impact was of these recurrent gene mutations.

And from this analysis we can see that there are differences, the prognostic impact is different in IgHV-mutated and unmutated CLL. So, for both groups, for instance, SF3B1 mutations, they had impact in both subgroups. Whereas other gene mutations had an impact only in IgHV-unmutated or only in IgHV-mutated CLL. So, in the end we performed multivariate analysis to see which ones were the strongest. And what we can see is that within the IgHV-mutated group, there are a number of gene mutations that give a worse outcome for these patients. So by analyzing a number of recurrent genes, we could actually identify patients with a worse outcome within this group that is supposed to have good survival.