Does CLL Treatment Cause CLL Cells to Become Stronger and Harder to Treat?

Experts responded to listener questions during our January 13, 2023 virtual town hall. Watch the full webinar here.

Jeff:    

Dr. Wierda, Matt would like to know do CLL active cells become stronger with each treatment, effectively making them harder to treat?

Dr. Wierda:    

That’s a great question. If we only had chemoimmunotherapy to talk about, I would say yes. We have a lot of historical data that demonstrates that each remission is shorter than the prior remission, and the likelihood of achieving a complete remission with retreatment with chemoimmunotherapy is lower than it was with the first treatment. So if we’re talking about chemo – chemoimmunotherapy, that is definitely the case. With targeted therapy – and when I talk about targeted therapy, we’re talking about BTK inhibitors, we’re talking about venetoclax (Venclexta) or BCL-2 inhibitors, that’s not quite as clear.

I think what happens with the chemotherapy and exposure to chemotherapy is that you select for the more aggressive cells that divide more quickly. The chemotherapy may also itself be causing some damage to the cells that allows them to grow more rapidly. That’s not as clear with targeted therapy. We see patients responding with venetoclax-based therapy. There’s not enough data to really clearly make a strong statement to answer that question with targeted therapy, even with venetoclax-based therapy. Because we haven’t treated enough patients, I don’t believe – or retreated patients with venetoclax-based therapy, after they’ve had first-line venetoclax.

Now the BTK inhibitor is a bit different because you give that treatment until regression, or until it doesn’t work any longer, so it’s – that concept may not apply as directly as it does to the venetoclax fixed duration treatment. Essentially, with targeted therapy, I really don’t believe we have enough data yet to make a clear, concrete statement about that. With chemo, yes. But it’s looking like it may be less of a situation with the targeted therapy.