Every patient’s CLL is different, so how do doctors tell which CLL treatment is best? Dr. Kathryn Kolibaba, with Compass Oncology, and Dr. Stephen Spurgeon, from OHSU Knight Cancer Institute, discuss modern tests used to distinguish subtypes of CLL and find a therapy to match. The experts also share their thoughts on the optimal timing for testing.
Dr. Kolibaba, so I said at the beginning, not everybody’s CLL is alike. So you do tests. Somebody comes into your office, you see their white count, you decide it’s CLL, but one patient’s CLL might not be the same as another. So what tests are you doing now to take a look at the subtype of CLL, which then might line up with different medicines or trials?
Sure. First, let me say I wish we had a test that would say what the right drug was. And we don’t have that now, but we would want to start with knowing where the immunoglobulin heavy-changing is mutated or not. So that IGHV mutation status we know to be key for outcome. And that might determine how often we see someone in follow-up, and what treatment we choose. So that would be one of the starting test.
And this FISH testing, I think it’s called?
Yep, FISH is another standard test. In that test, we can analyze cells that are not dividing with fluorescent probes and see what the DNA chromosome structure is like. And again, we’re able to identify CLL disease that’s at higher risk, or at lower risk for progressing rapidly, and we might choose treatment on that basis. And that changes over time but what’s definitely required at the start.
Okay, Dr. Spurgeon, do I have it right that you characteristic, my characteristic, their characteristic of CLL can mutate? That the cancer can change, and so the medicines that line up with our version of CLL at that time may have to change, too, right?
Definitely. Just a little comment about the analysis. So we’ve got FISH, we’ve got mutational status of the IGHV. There’s also genetic sequencing, targeted sequencing. The key thing we really want to know at this point for those things is being able to prognosticate the best we can, right? And also matching up a therapy. There are certain things we find that can be associated with no response to chemoimmunotherapy, or very limited response to chemoimmunotherapy. In particular, p53 mutations or 17P deletions.
The way our practice goes, is that we typically have a discussion what patients want to do out of the gates. So I guess my bias is not everyone needs all these tests at diagnosis. Unless you’re considering a high-risk clinical trial, as Dr. Keating was alluding to, patients—thinking about a trial of treatment early, again only in a clinical trial. Outside of that is, the key thing there is, if you don’t want to know all those specifics of what bucket you go into—because we’re still gonna be following you regularly. In my opinion, that’s okay. The key thing is getting these tests before you start treatment, and I think in this day and age, especially the FISH, that’s the most relevant.
The other factors that are important, or that are gaining more importance but are not so important in this day and age of new therapies, or we don’t know if they are yet, are some of these molecular testing.
So that’s actually not the chromosomes we look at, but specific genes to see if there are mutations, and there are really three that come to mind, I think, that are most relevant. One is P53; that is involved in, when you give someone chemotherapy or a treatment, it turns on P53 to kill cells. If you have a mutation in P53, well guess what? You can’t kill cells properly with chemotherapy.
Number two is another mutation called SF3B1, which is a mutation in the spliceosome, we won’t go through the nitty-gritty of that, but essentially that can be found in 10 to 20 percent of patients as well and has been associated with more aggressive and more quickly progressive disease.
The last one is a notch mutation, which is another mutation found in about, again, 10 to 15 percent of overall patients and much higher in patients with trisomy12, which is a FISH abnormality. All those things that I just mentioned have been associated with worse outcomes in people getting chemoimmunotherapy.
The issue is now, though—the challenge now, when we start sifting through all of these data—we are operating on the premise that these patients have gotten chemoimmunotherapy. So, the long-term data sets of new therapies have not caught up to some of these prognostic markers. But what it looks like is these new agents, for the most part, can overcome some of these poor prognostic factors. So, the bottom line is, everyone’s disease is a little different, and we can have different tests to help put people in different buckets. But to me, it’s most relevant when we’re about to start treatment or at relapse.
Published By :
Dec 11, 2017
Original Title :
Detecting, Identifying and Treating Subtypes of CLL