Blood Cancer Therapies May Play a Role in Treating COVID-19

Members of a family of targeted drugs used to treat blood cancer, known as BTK inhibitors, may be helpful in treating COVID-19, and some of these medications are being tested in clinical trials, experts explained in CURE®’s first-ever live webinar.

Sponsored by Janssen and Pharmacyclics, the webinar, titled “Hear from the Experts: COVID-19 & Cancer Care for Patients,” was designed to provide those affected by chronic lymphocytic leukemia (CLL) and multiple myeloma with information and updates on cancer care during the uncertainty of the COVID-19 pandemic. Topics included whether patients taking BTK inhibitors to treat their cancer should remain on such drugs if they develop COVID-19.

CURE® invited patients, survivors, caregivers, advocates and health care professionals to attend the panel discussion. Dr. Saad Usmani, chief of the plasma disorders program and director of clinical research in hematologic malignancies at the Levine Cancer Institute in North Carolina, served as the webinar’s moderator. Panelists included:

• Dr. Zainab Shahid, medical director of bone marrow transplant infectious diseases at the Levine Cancer Institute
• Dr. Farrukh Awan, director of the lymphoid malignancies program at the Harold C. Simmons Comprehensive Cancer Center at UT-Southwest in Dallas, Texas
• Dr. Ian Flinn, director of the lymphoma research program at Sarah Cannon Research Institute in Nashville, Tennessee
• Lee Greenberger, Ph.D., chief scientific officer at the Leukemia & Lymphoma Society in Philadelphia

In the talk, Drs. Shahid, Awan and Flinn addressed clinical trials that are underway to assess therapeutic approaches to COVID-19, as well as what role BTK inhibitors might play in treating the virus.

Shahid: We know that clinical trials are wide open for COVID-19. Last I looked, there were more than 200 clinical trials. So, we have to be good advocates of good agents that would be useful for the treatment of SARS-CoV-2 (COVID-19) infection. We know that there are clinical trials looking at agents that are geared toward treatment after exposure to prevent the development of infection, and antiviral agents that have been planned to be studied in acute myeloid leukemia (AML) patients are now being moved toward SARS-CoV-2 after exposure. We know that an agent that was being tested for influenza virus infection, called DAS181, is also in a clinical trial in the U.S.

Another antiviral agent, remdesivir, is already under investigation; however, trial sites may not be widely available because of a shortage of the study drug.

As we’ve observed the disease, we know that a week after the initial infection, people can do poorly if cytokine release storm sets in (meaning that the body’s immune system attacks healthy organs, such as the lungs).

As for anti-inflammatory agents, anti-IL-1, anti-IL-6 receptor blockers, anti-IL-6 blockers, tocilizumab (Actemra) and siltuximab (Sylvant) are being investigated in clinical trial settings to see if they can be utilized to decrease the severity of inflammation and improve outcomes in this patient population. Similarly, myocarditis (inflammation of the heart muscle) has been associated with the cases of severe COVID-19 in which these anti-inflammatory agents are being investigated. We know that convalescent serum (fluid from the blood of patients who have recovered from COVID-19) is being utilized in the clinical trial setting, as well. So there are many, many approaches that are being evaluated to improve the outcomes associated with the disease, but we do know that the trials take time.

Usmani: Speaking of agents that may have activity in COVID-19 disease, I want to ask Drs. Awan and Flinn about BTK inhibitors and some of the anecdotal data that we are hearing.

Awan: I think there are two ways to approach this issue. One is the drugs that are targeted toward the virus, and I think that’s a very critical part, so we need to start those early. We need to start treating patients who may not be very sick and hopefully we can prevent them from getting sick. I think the next approach is using all of these other agents — and there are so many of them that are being evaluated — to provide supportive care by not necessarily killing the virus but by reducing the inflammation and protecting different organs. I think ibrutinib (Imbruvica) and similar BTK inhibitors are already in trials, using these agents in patients with a lot of lung problems and hoping that that would reduce the inflammation and that would make our patients recover faster. That's very promising and very exciting.

Another thing that we have seen, which, again, is being debated in the field right now, is a situation I faced a few days ago. My patient was on a clinical trial with ibrutinib (to treat cancer) and she developed COVID-19 disease and within literally hours her oxygen levels dropped tremendously, and we had to put her on a ventilator. The big dilemma is: Should I continue ibrutinib or should I stop the ibrutinib? I don't think that there is a right or wrong answer because, technically, this would be considered a side effect so I would have to stop the drug based on the trial parameters, but there is some justification to continue the drug because that can reduce the inflammation in the lungs and the patient can recover faster.

The other thing that I feel is also very important is that patients with COVID-19 are being reported to have blood clots in the legs and also in the lungs and the BTK inhibitors also have some blood-thinning properties, so there might be some protective benefit through that mechanism. Will that be enough so that we don't have to use blood thinners in those patients? I am not sure. I think these are exactly the questions that need to be answered in clinical trials.

There are so many different drugs out there that we really have to decide, at this point, where do we focus our energies? Where do we focus our resources? We have treated more than 50 patients at our center with remdesivir because the idea is that if we stop the virus from getting worse then we can prevent the complications. Will that be the approach moving forward or will we use (medications indicated for blood cancer)? Will we use selinexor (Xpovio) because that's in clinical trials? Will we use acalabrutinib (Calquence)? Will we use ibrutinib and so many other drugs that are very promising and that have a very sound preclinical rationale of why we should use them?

But I think, at this point, the resources are really limited. Staffing is limited and, obviously, we want to do the best for our patients, so we have to just guess and hope for the best.

Flinn: There are a number of very compelling anecdotal reports of patients heading to the ventilator and taking one of the BTK inhibitors and maybe transiently going on the ventilator and coming off and then getting discharged soon thereafter. Some of these things are amazing. They are all anecdotes, and it’s hard to know whether another person would necessarily have a similar course. We're seeing this debate now with hydroxychloroquine and whether that helps. There was so much data that it couldn't hurt, but a report just out suggests that there is at least a population of patients in a retrospective analysis that had a worse outcome with it.

I think there is a lot that we don't know and they're very important scientific questions. Some of the things we're hearing about BTK inhibitors and other drugs is that they’re designed to dampen the inflammatory reaction and keep some of those bad pulmonary symptoms and progression of the disease in check. That’s the hypothesis there.

I certainly wouldn't put a patient on a BTK inhibitor outside of a clinical trial for treating COVID-19. I know that there is a lot of debate for patients with lymphoma and CLL who are already on a BTK inhibitor as Dr. Awan was mentioning, and whether you should take them off. Different institutions have different approaches. Personally, I would be afraid to take someone off if they've been on a BTK inhibitor for very long because sometimes you get that withdrawal inflammatory reaction and I could imagine you might actually make things worse. I think we all have to admit we don't know what the right answer is to these things and try to study them in a controlled manner and so, hopefully, three to six months from now, we're smarter than we are today and have a more appropriate approach.