BTK Inhibitors in the Presence of 17p Deletions or TP53 Mutation in CLL


Susan M. O’Brien, MD, on treating patients with 17p deletions and TP53 mutations who have chronic lymphocytic leukemia.

Susan M. O’Brien, MD: There’s 1 group [of patients for whom I] always use BTK inhibitors, and those would be the patients who have a 17p deletion or a TP53 mutation. That’s based on information from 2 trials. One is the venetoclax [Venclexa]–obinutuzumab [Gazyva] trial [NCT02242942] where, although with 4-years to follow-up, there is no median PFS [progression-free survival] reached yet. There is a median PFS in that high-risk group. That was about 4 years, which is still quite good and much better than we would have ever gotten with chemotherapy in that population, but nevertheless, it’s about 4 years. We have data from last [American Society of Hematology Annual Meeting] looking at combining 4 trials that use frontline ibrutinib [Imbruvica] to look at the outcomes of patients with 17p deletion or TP53 mutation. Why do we have to combine 4 trials? The good news is that that population is generally a very small fragment of frontline patients. It’s a very common clonal evolution where patients who are developing resistance to therapies are likely to have 17p [deletion] or a TP53 mutation, but not in the upfront population. Any given trial generally doesn’t have a lot of those patients. But this pooled data provided the biggest data source ever, which was 89 patients with 17p [deletion] or TP53 mutations who got treated upfront with ibrutinib, and the 4-year progression-free survival was about 78%. Clearly, patients with 17p deletion have remissions that appear to be lasting longer than they would with venetoclax. What we don’t know is [whether or not] ibrutinib is just a better drug than venetoclax for that subset or is finite therapy not a good idea in that subset. If I felt like there was a patient for [whom] I didn’t want to give a BTK inhibitor—and I’ve already stated that I can hardly think of what that setting would be—but if I did give them venetoclax-obinutuzumab, I’m not sure I would stop at 1 year. I might leave them on continuous therapy. But if I’m going to use the regimen as it’s FDA approved, then in that setting, I’m definitely going to go with my BTK inhibitors because the data are better.

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