Dr. Leslie:
So one unique thing about blood cancers, CLL included, is that not all patients with a diagnosis need treatment. And many patients can be on observation, enjoy treatment free periods before they ever get or need therapy. There have been studies in CLL showing that early initiation of therapy for patients does not improve how they do longer term. And I have patients who have had CLL honestly longer than I've been alive and have never needed treatment. So, there's really no need to start early unless a patient has symptoms. And symptoms can be something a patient feels or something the provider sees on the labs or on the imaging or on the physical exam.
What Are Common Signs That a Patient May Need to Begin Treatment?
Dr. Leslie:
So things patients look out for, I usually advise them to look out for unintentional weight loss, feeling like you get full early. So, if the spleen starts to enlarge, it sits right over the stomach, and that can make people feel like they used to eat a whole meal and now eat a few bites and get full because the spleen is making a stomach that used to be this size, feel like it's this size. So that early satiety is something I really always advise patients to look out for. If you feel any lumps or bumps or lymph nodes growing, if you're just really fatigued and there's no reason why, drenching night sweats really without any reason why, all of those things are general things to look out for. Other symptoms can be if [you] have anemia or low platelets, you can feel really tired. You can feel like you have your heart racing when you do minimal activities, bruising, easy bleeding. Those are all things that I always suggest patients call me or their CLL provider if they experience between visits.
What Are the Frontline Treatment Options
Dr. Leslie:
There are a number of different options for patients with newly diagnosed or newly needing treatment CLL. And we used to use a lot of things like chemotherapy with immune therapy. And since around 2014 or so, we've shifted away from chemotherapy and now use targeted therapies or non-chemo approaches for the vast majority of patients. Even over the past five years, I can say the number of patients I consider using chemotherapy for is very small, maybe one or two a year. And I have hundreds of CLL patients under my care. So, it's really a very, very small minority, a rare group of patients where we consider chemo. That's because the newer therapies, the target therapies, are better tolerated and also are more effective.
So one thing that's important that your doctor will do before deciding a treatment is checking your special blood work. That can help predict which type of treatment might be helpful for you and what your outcome should be with that treatment. And then the usual decision is between two classes of drugs. One is called Bruton's tyrosine kinase inhibitors or BTK inhibitors and the other is called a Bcl-2 inhibitor or venetoclax (Venclexta). And these two groups of drugs are very different. The first group, the BTK, this targets a protein that the CLL cells are addicted to.
So this growth loop is just going and going when it shouldn't be. So, what these groups of drugs do, which examples of that are ibrutinib (Imbruvica) and acalabrutinib (Calquence), which are approved, zanubrutinib (Brukinsa), soon to be approved [for] CLL. So, there's three of these drugs and they block that loop. And then the cells are released from the bone marrow, so the white blood cell count goes up. And then slowly with time, it comes down. These drugs are used as now indefinitely. So, you start it, and you stay on it long-term. If patients come off therapy, usually the white count starts coming up. So that's the one group, target that growth loop.
The other group targets a protein called Bcl-2, which is a survival protein. The name of that drug that's approved is venetoclax. So, what that is is CLL cells or lymphocytes should live about 10 days and a CLL cell lives 100 days. And that's because it has extra survival signal saying, “You should survive.” When really that cell's lived its life cycle. So, when you start that type of drug, you turn off the light switch. That survival signal is turned off and all the CLL cells can just die pretty quickly. And that can cause something called tumor lysis.
So unlike the first drug where you just start the BTK and see your doctor maybe two weeks later to check in, with the second groups of drugs, venetoclax, you start at a low dose and ramp up over five weeks so that you don't have that problem when the CLL goes away too fast. Also, because it's turning off the survival signal, if you're using it in the frontline setting, that treatment's only for one year. So, there's a lot of differences between how the drugs are given, what to look out for, and the longer-term plan. But they're both very well tolerated treatments and can both be given with immune therapy as well. Venetoclax is always given with an immune therapy, a CD20 antibody called either rituximab (Rituxan) or obinutuzumab (Gazyva). And then the BTK inhibitors can be given by themselves or with an immune therapy as well. So, there's a few different options that might be appropriate for your case.
I'm talking about these treatment options with patients newly diagnosed or relapsed/refractory. Most [the] time I'm talking about, do we do a long-term Bruton's tyrosine kinase inhibitor usually by itself or do we do venetoclax with a CD20 antibody immune therapy for a time-limited period? And a lot of that is how old is the patient? If I've got a 30-year-old, the thought of a forever medication is completely overwhelming. If I have a 95-year-old or a 98-year-old, if I say, “You're on this long term.” They say, “A year, whatever years I have left, means nothing to me.” Which is better tolerated. Side effects are different, so if someone has some cardiac issues the Bruton's tyrosine kinase inhibitors can cause bruising and bleeding, they can increase the risk of atrial fibrillation, which is an irregular heartbeat. So that's something we take into consideration.
With venetoclax or the time-limited one year program, that can cause tumor lysis or the CLL cells to die too quickly. So, if someone has underlying kidney disease or can't get a lot of IV fluid because that would be hard to tolerate, maybe that's not the best choice. There are some drug-drug interactions, so if a patient has to be on a proton pump inhibitor, some of the BTK inhibitors won't be absorbed. So, you take into account the age, the goals of the patient, the comorbid conditions or the other medical conditions. And it's really encouraging to say, “I've got these great options, both will be wonderful for you, both are well tolerated, which works best for your life?”
