Treatment Updates for Patients with TP53 and 17p Deletion

Our recent CLL Global Research Foundation Town Hall featured CLL Global President, Dr. William Wierda, and Dr. Constantine Tam from Monash University in Melbourne. CLL patient advocate Jeff Folloder moderated the event. Watch the full webinar.

Transcript

Jeff Folloder:                          

Dr. Tam, Peggy has a great question. Is there any new information on treatment protocols for CLL, specifically with folks who have the TP53 feature and the 17 deletions?

Prof. Constantine Tam:          

So, for the audience, the 17p deletion or P53 mutation, they go hand in hand. Basically, means that there has been disruption of a key gene in the CLL cell called P53. And that gene is responsible for response to chemotherapy. So, in the era where we used to use chemotherapy, there was a really important gene. If you have P53, you are not going to respond to chemotherapy, you get all the side effects, but you won’t get any of the benefits.

So, in the modern era where we have targeted therapies, in general, the BTK inhibitors, such as acalabrutinib is thought to largely overcome the bad impact of P53. So, a patient who goes on to acalabrutinib with P53 is going to have a similarly good outcome as their patient who doesn’t have P53. And that’s not exactly true of the venetoclax-based regimen.

So, if you take a venetoclax-based regimens and you have P53, your response duration tends to be a bit shorter than patients who do not have P53. So, there is a general trend to go towards the continuous BTK therapy for patients who have got P53, and slightly away from the venetoclax-based fixed duration regimens. But that comes with important a caveat. So, just in general.

I think in my practice; the most important thing is patient preference. And for my patients, the question is, “Do you want to have a continuous, easy-to-take, suppressive therapy? Or do you want to put in the work for a slightly more cumbersome, but a fixed duration therapy, with venetoclax?” And if my patient has P53, and says to me that they strongly about having venetoclax because they don’t like continuous therapy, I don’t think that’s a wrong option. Because you will still get approximately four years of venetoclax-based therapy.

And as Dr. Wierda has already alluded to, the important thing about the fixed duration therapy is, at the time when you relapse, yes, you may actually stay in remissions for longer. It’s so long, compared to continuous therapy, but when you relapse, you do not carry recessive mutations. And you can still be re challenged with the same drug, and be retreated, and go back into remission. Okay?

So, if you take a BTK inhibitor continuously, and yet, your CLL gets worse, well, you’ve developed resistance to a drug, and you can’t ever go back to that drug again. For venetoclax, you just take it, you stop it. If some years later, it comes back, you can be retreated and go back into remission. So, the first remission duration may be shorter, but there’s an option for retreatment. So, I think overall, it balances to be about the same.