Published on July 28, 2020
How Long Will Remission Last With New CLL Drugs?
How do new oral drugs affect CLL remission rates? Jennifer A. Woyach, MD, Associate Professor, Division of Hematology, The Ohio State University and Patient Power co-founder and CLL patient, Andrew Schorr discuss how new oral CLL medications affect remission rates and length. They discuss how these new chronic lymphocytic leukemia drugs have been proven effective in clinical trials with patients still in remission and their effectiveness in treating CLL in patients who's treatment stops working.
Transcript | CLL Remission Rates With New Medications
Hello and welcome to Patient Power, I'm Andrew Schorr. And for 24 years I've been a CLL patient. Joining us from the James Cancer Center at the Ohio State University, is Dr. Jennifer Woyach, who's a CLL specialist. Dr. Woyach, so you have these oral medicines now that people have been taking ibrutinib (Imbruvica), acalabrutinib (Calquence), venetoclax (Venclexta), and people say, well, how long is it going to last? Because people have some understanding that cancer is pretty wily and it tries to, at some point, outsmart the drug. And I think you call that resistance. So, where are we now with understanding resistance as these drugs are used longer?
So, the good first news is that these oral medications for CLL are very, very effective. And depending on a lot of factors including how many prior therapies' somebody has had with the genomic risk of their disease is and other things. The remission time on any of these medicines, ibrutinib, acalabrutinib, venetoclax with an antibody can be very, very long. For patients with previously untreated disease, one thing that is great is, we actually don't know how long these therapies are going to last because in the time that we have follow-up for patients, most of the patients are still in remission. For example, with ibrutinib on the RESONATE-2 study, which is the longest randomized trial that we have data on in the upfront setting, at five years, 70% of patients were still in remission. So, that's phenomenal and we don't really know what's going to happen after that point. Hopefully, many of those people will remain in remission for another five years. With the other drugs, that those roads are a little bit newer. So, we have even less data on how long people will do. But the short answer is very, very well.
For patients with relapsed CLL, many of these drugs can still be expected to produce remission durations at least four years, on average. One thing we're starting to understand better and better too, as we've used these drugs longer, is that you likely can go from one class to the other very successfully. So, we knew this first about a BTK inhibitor and then venetoclax because that was actually done in the context of a study where we know that after somebody has progressed on a BTK inhibitor specifically, ibrutinib.
If they go on venetoclax as a single agent, the median progression-free survival and median remission times about two years. And this is really variable too. So, patients who are treated in earlier lines of therapy for their BTK inhibitor are likely with their became a better, are likely to have longer remissions. When venetoclax is given with rituximab (Rituxan) or with obinutuzumab (Gazyva), it seems to last longer than when given by itself. And we now have some data in the other direction too. So people who are initially treated with venetoclax plus obinutuzumab, or venetoclax plus rituximab can then go on to a BTK inhibitor and do so successfully as well.
We're starting to understand better and better to why patients relapsed on these drugs. With ibrutinib and with acalabrutinib, primarily, it's that patients will develop mutations in their cancer cells in BTK, which is the binding site of the drugs. And that changes the binding of the drugs that makes them less effective. The same thing can actually happen with venetoclax, although since the venetoclax is given for a shorter period of time, we don't really know yet if giving somebody venetoclax for a year, if they're going to develop mutations at that point, or if it really takes three, four years on the drug to develop those mutations. So, these are all areas that people are really actively investigating and I think we're going to know more and more in the next few years.
One other question, and that is about combination therapy. So, let's say somebody was on one of these drugs by itself or let's say venetoclax and obinutuzumab. They've been on that, but then their disease comes back where they progress. Could you then switch to a combination that still included that original drug and get a second chance?
So, that is a great question and I don't think we know for sure, whether that will work for every patient and when it does work, we don't entirely know why. So, for example, we know that somebody who is on ibrutinib develops a BTK mutation and relapses. They can go on to venetoclax and if the venetoclax stops working, we know that those patients actually still have BTK mutations. Interestingly, even if it's been years since they had ibrutinib, but many times you can actually give those two drugs together, ibrutinib and venetoclax and still get a short remission, at least. So enough time to get to a clinical trial or to CAR T-cells or something like that. So, yes, to answer your question, you probably aren't going to get as long of a chance as you had the first time you had the drug, but definitely those drugs can be useful even after patients progress to get to something else.
Okay. Well, I want to end where we began and that is the good news is, many people are on these newer drugs for extended times and we don't know how long they're going to last or how long that they may be a very extended remission and that's great news. Dr. Jennifer Woyach from the James Cancer Center at Ohio state, Thanks for being with us.
Thanks for having me.
I'm Andrew Schorr. Remember, knowledge can be the best medicine of all.
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