GU Cancers 2021 | Association between TMB and irAEs during ICI therapy in patients with mUC
Guru Sonpavde, MD, Dana-Farber Cancer Institute, Boston, MA, discusses the results of a retrospective analysis investigating the association between tumor mutational burden (TMB) and immune-related adverse events (irAEs) in patients with metastatic urothelial carcinoma (mUC) during immune checkpoint inhibitor (ICI) therapy. The study, which analyzed data from 101 patients with mUC who had previously been treated with an ICI, found that higher TMB was associated with a higher incidence or irAEs. Patients with high TMB and high irAEs had better response rates compared with those with only high TMB or high irAE, suggesting the possibility of complementary tumor and host characteristics. This interview took place during the 2021 Genitourinary Cancers Symposium.
Transcript (edited for clarity)
We did a retrospective study at the Dana-Farber Cancer Institute, where we looked at the patients with metastatic urothelial carcinoma who received an immune checkpoint inhibitor. And we looked at the association between the tumor mutation burden, or TMB, with the immune-related adverse events. And what we found was that there was indeed a strong association between TMB and immune-related adverse events...
We did a retrospective study at the Dana-Farber Cancer Institute, where we looked at the patients with metastatic urothelial carcinoma who received an immune checkpoint inhibitor. And we looked at the association between the tumor mutation burden, or TMB, with the immune-related adverse events. And what we found was that there was indeed a strong association between TMB and immune-related adverse events. Now, what we also know historically is that there is an association between tumor mutation burden and the response to immune checkpoint inhibitors. So we found this interesting and essentially, the hypothesis for this product was that mutation burden which, of course, leads to neoantigens, might also be associated with the immune-related adverse events because the activity against these new antigens may also be the source of the genesis of these immune adverse events.
So, we did find a strong association between IRAs and TMB. And interestingly, when we looked at the response of these patients, the combination of TMB, tumor mutation burden, and IRAs added to the association with the response. So really, they both give complimentary data we think, in terms of the host, which might be responsible for or, either, immune-related adverse events, as well as the TMB which is a tumor characteristic.
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Disclosures
Dr Guru Sonpavde, MD, has participated in advisory boards for BMS, Genentech, EMD Serono, Merck, Sanofi, Seattle Genetics/Astellas, AstraZeneca, Exelixis, Janssen, Bicycle Therapeutics, Pfizer, Immunomedics/Gilead, Scholar Rock and G1 Therapeutics; has received research support from Sanofi, AstraZeneca, Immunomedics/Gilead, QED, Predicine and BMS; has had travel costs reimbursed by BMS and AstraZeneca; has received speakers fees from Physicians Education Resource (PER), Onclive, Research to Practice and Medscape; has received writing fees from Uptodate and is Editor of Elsevier Practice Update Bladder Cancer Center of Excellence; and has participated in unpaid steering committees of trials or studies with BMS, Bavarian Nordic, Seattle Genetics, QED, G1 Therapeutics, and in paid steering committees of trials or studies with AstraZeneca, EMD Serono and Debiopharm.
