Evolving Therapies in Chronic Lymphocytic Leukemia - Episode 8
Nicole Lamanna, MD: Lately, medicine has been challenging for all given the ongoing coronavirus pandemic. I’m in New York, so we had a busy March and April. This is something we’re facing until we have either a vaccine therapy that’s very effective or treatment options for patients who develop an infection from the coronavirus, that we know we can successfully treat them as we do other infections or viruses, depending on what that virus is. Many of us are clearly on edge given what we went through in New York and my experience with COVID-19 [coronavirus disease 2019] in our CLL [chronic lymphocytic leukemia] patient population, and certainly I do think our patients are at a higher risk of complications from COVID-19. Hopefully there will be data forthcoming about that, because we’ve put some data together. There have already been some publications from abroad looking at cancer patients in general and how those patients don’t do as well from COVID-19 as opposed to noncancer patients, but certainly I think our CLL patients are at risk for complications.
In terms of treatment, this is something that’s going to evolve, and we’re going to need more data to elucidate if that’s going to be a problem. I don’t necessarily recommend that patients start earlier or do things differently in terms of when they need treatment for their CLL. I still recommend active observation and monitoring until such time that the disease really requires therapy, so we’re not treating patients necessarily earlier because of the pandemic. There’s no doubt when you have these conversations with your patients and you’re talking about options of therapy, when you’re talking about oral therapies versus oral, IV [intravenous]. or hospitalization and monitoring and more frequent visits and things like that, having an oral BTK [Bruton tyrosine kinase] monotherapy is certainly more appealing to patients.
Obviously, the frequency of their office visits and adverse-effect profiles tend to be obviously less than the monitoring required for a venetoclax–antibody combination. That needs to be taken into consideration in a discussion with your patients. We will probably see more favored use with the BTK possibly in that setting or discussion coming out because patients are still nervous about coming to their doctor’s office or to a hospital if they need a hospitalization.
I don’t think our recommendations should be different. We have great therapies available on both fronts: time limited versus BTK. Those discussions are still all relevant and paramount, but patients may choose to do that because in the beginning. Regarding the ramp-up, they really need to be monitored more closely. Are there ways to finesse that ramp-up? Are there differences? Can we start with an antibody and debulk the patient and then can do the venetoclax as an outpatient? There are clinical trials that looked at this already.
Certainly, we know that doing that can potentially debulk patients sooner and then have them do this as an outpatient. This leads into some of the combination strategies that are being evolved prior to the pandemic when we look at combinations such as ibrutinib and venetoclax or a BTK inhibitor and venetoclax. If you look at those combinations, then you can debulk them as an outpatient and then do venetoclax ramp-up as an outpatient as well. Different combination strategies can do that to make the ramp-up easier for our patients. They may not require hospitalization then, but they still need to be monitored. Even if the venetoclax ramp-up is going to be as an outpatient because you’ve debulked them adequately and they’re no longer high risk, you’re still going to have to monitor their electrolytes; they’ll still need more frequent lab checks because they’re still doing that 5-week ramp-up even if it’s as an outpatient. That still needs to apply regardless. There might be more frequent issues, but you might avoid the hospitalization. There are ways to think about how to strategize those patients.
Of course, the BTK-venetoclax combination is still in clinical trials, and it’s appropriate that those individuals in clinical trials do that because we’re trying to learn about that combination. We know it’s effective. The combinations, whether it’s with a BTK and venetoclax or other combinations, we know that in frontline therapy, these combinations are very active and have high efficacy. Ultimately, we’re trying to learn what is the response duration of these combinations? What is the progression-free survival of these combinations? Are we doing something different? When patients relapse, how do we salvage those patients? If they’re not approved, I still argue that those patients should be put on a clinical trial so we can monitor the effects of these novel combinations, so we’ll gain information about how to sequence therapies, how to salvage patients with therapies because we don’t have that data. There are many ways to use CD20 monoclonal antibodies to debulk patients if you’re going to use venetoclax and then strategize that for doing outpatient therapy, and that data are certainly there and available and can be used. For some of these more novel combinations, I still argue that patients should be on clinical trials to evaluate them for how they do.
Transcript Edited for Clarity