Evolving Therapies in Chronic Lymphocytic Leukemia - Episode 5

COVID-19 and CLL Treatment Initiation

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William Wierda, MD, PhD: Let's hear a little bit from Dr Allan in terms of what his experience has been in regard to COVID-19 [coronavirus disease of 2019], if it's been any different, and if he has any helpful suggestions or recommendations for us.

John Allan, MD: Absolutely. So, obviously, this is an evolving time that we live in now. I think we have to prepare and expect that COVID-19 is here to stay; it's not going anywhere anytime soon. Essentially, we have to prepare for that expectation for our patients. In my experience, obviously this is a devastating disease. This is something that we do not want our patients to get. We do know there is emerging data that chemotherapy patients, cancer patients on therapy in general are at a higher risk for poor outcomes.

We know that our patient population, being older in general, has already one of the major risk factors for severe complications from the disease. We really have to do our best to protect them, and 1 way is encouraging social distancing, the mask, the hand hygiene, and really reiterate that. We know from health care workers that if you practice these very basic things, you can decrease your infection rate. I think that's important to get across to our patients as well as to our physicians. I think that's more recognized in our system.

With our patients with CLL [chronic lymphocytic leukemia], I have found when we are in this exponential phase, this is not a time when you want to be initiating treatment on a patient, for all the factors that Dr Shadman had spoken to about—minimizing interaction, the immunosuppressive effects of some of these treatments. Essentially if you have a watch and wait patient, you want to push them toward telemedicine, minimize labs, and schedule local labs where patients can avoid public transportation.

Obviously, if you have a very sick patient and they need to initiate treatment, you do have to make some decisions, but I think we are fortunate to have many options. BTK [Bruton tyrosine kinase] inhibitors are a great option for patients that need to get out of trouble. You can start a drug, sometimes you can have it delivered, and it has low toxicities. Then, you can do video visits with them, see how they're feeling, and get local labs at 2 weeks or a month later. That's a great way to get somebody out of trouble who needs treatment in that situation. There’s a VenG [venetoclax + obinutuzumab]-based approach when you need to ramp up, and there's obinutuzumab, an anti-CD20 monoclonal antibody, and frequent hospitalizations, so it's probably not ideal.

So, I think it's region specific. What I found now where New York has gone back to normal. We have low infection rates. We have low daily admission rates. I think in New York State, we only had about 30 total hospital admissions in the last day or so. If you look at our curve, we are maybe in total a couple hundred new coronavirus diagnoses a day. At this point, we are in a window of opportunity that at least in New York, we can go back to our previous thinking and reasoning for specific patients.

At this point in time, if there is a good patient that is eligible for a VenG-based approach, I'm not so scared to do that, though I think it's going to be region specific. If you're in a state or city where you're seeing increases like we are seeing in some of our states currently, where you’re increasing and even in an exponential phase, we don't know when that's going to bottom out. I can say that we are at high risk for having serious issues in some of those places where you don't want to be initiating treatment. It's all region specific. It's patient specific. If you can wait until you're on the downswing and the situation is better controlled, it's best to do that. Obviously, if you are in a situation where you need treatment and you are in a place where there are increased cases of this disease, discuss with your doctor, and maybe a BTK inhibitor approach is probably a little bit easier and more likely indicated.

We don't have any evidence right now that patients with anti-CD20 therapy or specific treatments have worse outcomes or more severe outcomes. I can tell you from just personal experience, I've had patients get sick that have had anti-CD20. They have gotten over it and took a little time to clear, but then they finally have developed antibodies and have cleared the disease. This is while being on a BTK inhibitor plus an anti-CD20. The anti-CD20 for several months prior and was done. They had severe complications, but they had other risk factors—hypertension, renal insufficiency, and some of these things that we get concerned about. I’ve had patients in their 70s who are on a BTK inhibitor but are relatively healthy, get the disease, and have very mild, minimal symptoms. I’ve had other patients on watch and wait have very mild, minimal symptoms. I've had people on watch and wait get hospitalized but not ventilated. I've also had many patients with CLL just properly doing infection control, social distancing, not even get the disease.

I want to reiterate to patients and other physicians out there that just because the patient with CLL is going to get sick does not mean he or she is going to have horrible outcomes, though they are at risk for those things. I think that over time, we're going to start to understand what types of treatments may put patients at risk.

In reality, I think what we've shown time and time again from just patients with COVID-19 that age, hypertension, kidney disease, diabetes, obesity, pulmonary disease are the things what really come together in a perfect storm, this inflammatory basal state that the patient has that tips over. Patients are dying from this inflammatory overwhelming condition that occurs with the virus that we haven't seen before and are still trying to grapple with and understand.

So, complicated answer to a tough question, but I think what the important take-home is: Watch your region. Watch the state you're in, and if you are in one of these places where it's not well controlled and it’s in an exponential, taking-off phase, you have to be careful and really think about your approach. If you’re in an area that is past that point, like we are in New York, I'm starting to tell my patients that it's safer to reengage with society. I'm now starting to think that my previous reasoning, if I thought that patient would benefit from a VenG-based approach pre-COVID-19, I'm comfortable doing this. I feel like there's a window of opportunity, though that could change in 3 months if we start to see a second wave. You just have to pay attention to your caseload and where the virus is specific to your region.

William Wierda, MD, PhD: I would agree. My thought has been that our patients are in tune to social distancing already, even before COVID-19, and they have good hand hygiene, which may have reduced the risk. But we haven't here seen that a diagnosis of CLL puts patients at an increased risk more so than any other factor that we already know about. Has that been your experience, John?

John Allan, MD: Our patients are immunosuppressed at baseline, and when we see our numbers and look at some of our data—I know there'll be data emerging with larger cohorts coming out, I'm sure, by the ASH [American Society of Hematology] annual meeting and others in the near future—we do see more serious complications in this patient population than what we would for all patients. But I think, again, that also represents our patient population. They're typically older. They have underlying CLL. So, some of that is based in those risk factors inherently. I do think that they are at greater risk for complications, so with that said, it's not everybody. It's not the majority, and most patients can be OK. A minority don't have major problems. There is a middle ground that they get hospitalized but they're not on the ventilator and all these types of things. There's also that other quarter to maybe a third or whatever it is that we see in our own practice and in our own ICUs [intensive care units] that have had very serious complications. Some have survived. Others have passed away. But it is something that I agree that our patients are at higher risk for severe complications.

Transcript Edited for Clarity