ICML 2025 | The impact of TP53 mutations and copy number loss on survival outcomes in patients with LBCL

Yes, so there are many factors which may predict poor outcomes for patients with newly diagnosed large B-cell lymphoma after standard frontline chemotherapy, and one of them historically has been TP53 mutations. However, those mutations sometimes come alongside copy number loss or are seen separate from copy number loss of TP53. And also there’s this concept of monoallelic versus biallelic TP53 loss that’s more well-known in myeloid diseases. And so we aim to look at all of these TP53 alterations to see if they impacted prognosis in a large cohort of patients treated with standard chemotherapy. We used a commercial sequencing panel that was able to look for TP53 mutations as well as copy number loss by next-generation sequencing. And we looked at clinical outcomes for all these patients who were treated at the University of Pennsylvania over the past five years. And we found that essentially the TP53 mutations and the copy number loss and the combination of both predicted for inferior two-year progression-free survival, although two-year overall survival was only impacted negatively by TP53 mutation. And we also found that these monoallelic versus biallelic classifications of TP53 alterations do not seem to affect prognosis. Prognosis, there are worse outcomes for patients regardless of whether they have a monoallelic or biallelic alteration. Of note, about 15% of patients had a TP53 copy number loss, about 15% a TP53 mutation, and then 15% actually had both. So in sum, it’s almost 40% of patients who have some sort of TP53 alteration who may do worse with standard chemotherapy when newly diagnosed, and we need to validate these findings and also add some additional patients to see if it would hold true.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.