Published on April 23, 2021
Experts Explain Frontline Treatment Options for CLL
What are the frontline treatment options for patients with chronic lymphocytic leukemia (CLL)? What are the differences between them? And finally, how do you choose the right one for you?
In this excerpt from a recent CLL Town Hall event, hosts Andrew Schorr and Carol Preston talk to Dr. Shuo Ma, MD, Ph.D., of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and Dr. Deborah M. Stephens, DO, of the Huntsman Cancer Institute at the University of Utah to answer these questions and more about the CLL treatment paths that are available today.
Support for this series has been provided by AbbVie Inc., Genentech, Inc. and Adaptive Biotechnologies. Patient Power maintains complete editorial control and is solely responsible for program content.
Transcript | What Treatments Are Available for Patients With CLL?
Carol Preston: But once you've decided, or the team has decided that a patient needs treatment, what's your go-to?
What Are the Frontline Treatment Options for CLL?
Dr. Ma: Right. So, I think we're really having a longer and longer list of treatment options for the frontline treatment, which is really a great kind of a luxury to have, I'll say. Because six, seven years ago, what we have is really just immunochemotherapy. So several of you, our host, had had the immunochemotherapy such as FCR, or chemotherapy plus monoclonal antibody, or some version of that. That had been the past gold standard. However, in the past five, six years, the standard is shifting. Now we have at least two classes of what we call: oral targeted therapies. So those are oral pills, which are targeting particular molecular enzymes, which are important for the lymphoma cell, the leukemia cell survival and proliferation. So by blocking this enzyme, you can really induce that of those leukemia cells as a treatment. So, the two classes are, one is what’s called BTK inhibitor.
So BTK is the target. And in that class, we currently have two FDA-approved drugs. The first one is ibrutinib, or Imbruvica, which is really the very first targeted therapy we have for CLL, which has already been there for six, seven years now. And then the newer comer is called acalabrutinib, or Calquence. That’s really – they both work the same way. They're both what's called BTK inhibitors that you take orally, either once a day or twice a day, continuously. This is a continuous chronic treatment; we don't stop unless the disease is no longer responding, or if the patient has an unusual side effect. So, that's one class of target therapy we have available. And both drugs can be used either by itself or combined with a monoclonal antibody, such as obinutuzumab (Gazyva), which Dr. Stephens mentioned previously. Previously we combined the monoclonal antibody immunotherapy with chemo, now we can combine it with the targeted therapy. So, that's the one class.
The second class of targeted oral therapy is what's called Bcl-2 inhibitor. So Bcl-2 is an important, protective protein that's in the cell death machinery. So, once you inhibit this protein using a Bcl-2 inhibitor, then you can actually induce cell death in leukemia cells very rapidly. So, the drug in this class is called venetoclax (Venclexta), starts with a V. Venetoclax is always used in combination with monoclonal antibody immunotherapy. So, in the frontline is combined with again, obinutuzumab. This treatment, the current FDA approval is for one year of venetoclax plus the standard six months of the immunotherapy. So, these are the standard options that are available, including immunochemotherapy, the BTK inhibitor or the venetoclax-based therapies.
Andrew Schorr: Dr. Stephens. So, there you have a patient in front of you and they're saying, "Okay, help me. How do I work through this choice?" Take pills for a long time or take pills and maybe an infused monoclonal antibody for a short time, and then take nothing for some length of time. How do you have that conversation when it seems like both directions are good, depending upon side effect profile, and I guess the way somebody wants to live, maybe their insurance.
What Advice Do You Give Patients During the Decision-Making Process?
Dr. Stephens: Yeah. I think these are really great questions. And when I start a patient on a new treatment, I find that I have the longest discussions with people because it's nice now that patients get to participate in shared decision-making about what is the best treatment option for them. As a physician, we can make recommendations about what we think is going to work the best, meaning what do we think is most likely to put them into remission, based on other medical problems, what is least likely to give them side effects and we can make a recommendation, but in the end it does sometimes come down to, would you rather do this continuous therapy with drugs, like Dr. Ma mentioned, the BTK inhibitors, like ibrutinib and acalabrutinib or a shorter therapy with venetoclax. Sometimes when people say, "Gosh, if I start ibrutinib, does that mean I'm going to be on this drug forever?"
And forever just sounds like a really long time, right? But to be honest, it's not always forever because some people can't tolerate the drug, they have side effects. Some people will end up relapsing on the drug. And as you've just heard, our field is moving forward so quickly, that who's to say that in two or three years from now, maybe we find a new drug that we add to ibrutinib, and then you are able to stop by ibrutinib therapy. I don't want people to be intimidated by the thought of "I'm going to be on this drug forever," because things change a lot over the course of years.