Nicole Lamanna, M.D.: Danise, when we talk about your clinical trial, obviously I know that you know what you got.
Danise Hoover: Yes.
Nicole Lamanna, M.D.: Danise participated in a trial with a drug that is now FDA approved.
Danise Hoover: Right.
Nicole Lamanna, M.D.: Actually, based on the study that she participated in.
Danise Hoover: Well, my friends would ask me, “How do you know you’re getting the experimental drug instead of the standard of care?” It was pretty easy because the standard of care was an injectable, and the experimental drug was an oral medication. So that was pretty straightforward.
It was a long process, and the hardest part was it took five weeks to get up to the full dose of the drug. We started out with very small doses, and I was closely monitored for all of that time. It involved more hospital admissions and longer stays, but again, it’s part of the experiment. They don’t know what it’s going to do to you, and so they have to watch. It would be worse to be away from the hospital and have a bad response. It was part of the agreement, to put up with whatever inconvenience there was.
Nicole Lamanna, M.D.: Danise actually happened to have participated in a clinical trial where patients were randomized to more chemoimmunotherapy, which is what she was offered if she wasn’t going to go on a study. So it was a bendamustine/rituximab regimen. This was not blinded. There are some trials, as Danise was referring to earlier, where you may not know what you are getting.
Danise Hoover: Yes.
Nicole Lamanna, M.D.: The doctor needs to tell you. It’s not one of those kinds of trials. It is rare. There are some studies where a patient may get a placebo, meaning they don’t know what the drug is. But usually, it depends on the context of that study. Let’s say somebody’s getting treatment that is standard, but they’re also getting a placebo. So they’re adding another drug. And so, the trial’s randomizing patients to get active treatment but placebo versus another drug to see whether that other drug may add a benefit to standard treatment. That would be a blinded study. But patients need to know that before signing consent or going on a study. You have to be told that.
Most studies are not blinded. With most studies, you know what you’re getting when you participate in a clinical trial. And so, her trial incorporated being on this new oral therapy. This was a drug called venetoclax, which is now FDA approved for patients with relapsed CLL [chronic lymphocytic leukemia] or patients who have CLL with a 17p deletion. Danise was randomized to receive this oral therapy. She did get rituximab in conjunction with venetoclax, so she got some intravenous [IV] therapy as part of this particular study.
And then, after a period of time, the study stopped. The therapy stopped. The venetoclax was completed. In other words, she got a certain course and then even her oral therapy was completed.
Danise Hoover: Yes. I took the drug for two years. At first, it was annoying to think about taking this drug for the rest of my life. And then when they said, “Oh, stop next month,” it was sort of frightening to think that I wasn’t going to take this drug for the rest of my life. But yes, I took the drug for two years and then stopped.
Nicole Lamanna, M.D.: There are a bunch of explosions of new therapies for CLL. We talked about traditional chemoimmunotherapy approaches. Venetoclax happens to be a new therapy that’s an oral drug. It’s called a BCL2 [B-cell lymphoma 2] inhibitor. CLL cells overexpress BCL2, and so this is an inhibitor. Think of it like causing the cells to die, if you inhibit this.
There are other targeted therapies for CLL as well. There has been an explosion of new targeted therapies for CLL that have been FDA approved over the last few years. There are BTK inhibitors, or Bruton tyrosine kinase inhibitors—ibrutinib being the first to market. There are what they call PI3 kinase inhibitors. There’s a slew of oral therapies available for patients with CLL that are targeted.
When these drugs first got approved, they were given chronically. So like your chronic condition, you would take them indefinitely. If you get started on a drug like ibrutinib, some of you might be on that, this would be a drug that you would take indefinitely right now. We’re learning to explore this, and I’ll talk more about that in a minute. But patients continue this as a daily oral therapy, like Danise was taking her venetoclax daily, unless somebody had a significant side effect to the therapy that they’re on or it stops working, of course. If the disease starts growing and it’s not working, then your physician would electively choose to treat you with something else.
When these oral therapies got approved, they got approved as chronic oral therapies. What was unique about the clinical trial that Danise was on, however, was that because of some of the earlier studies that were conducted with venetoclax, we knew that there were patients who could get deeper remissions with this drug compared to other drugs. And so this was exploring the idea of: Could we stop patients on their oral therapy? Does everybody need to take chronic indefinite oral therapy? Can we do something similar to what we did with the IV therapy that Danise got, meaning you would get a course of therapy, stop, and then monitor again.
Because that’s how we traditionally did this with the IV therapies. Can we do that now with these new oral targeted therapies? Danise happened to participate in a study where she got a course of treatment with venetoclax and rituximab, and then it got stopped. So she’s been off of therapy. Danise, your response to therapy so far?
Danise Hoover: It’s been absolutely perfect. There’s no sign of leukemia in my blood or in my bone marrow.
Nicole Lamanna, M.D.: So Danise has a true complete remission. There are therapies that can achieve this level of response, which is very deep. In other words, after you have been treated, no matter what therapy you get, you can look and evaluate how much CLL might remain. Danise is one of those patients who happens to be in a complete remission. You have been off of therapy for how long now?
Danise Hoover: A year and a half.
Nicole Lamanna, M.D.: She’s still in a complete remission and has been off of venetoclax since that time period.
Danise Hoover: Right.
Nicole Lamanna, M.D.: So kudos.
Danise Hoover: Thank you.
Transcript Edited for Clarity