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Published on December 11, 2020
In COVID Times, What’s a Transfusion or Phlebotomy Dependent Patient To Do?
Having to account for the logistical, emotional, and medical ramifications of COVID-19 can be overwhelming for anyone. For myeloproliferative neoplasm (MPN) patients who are transfusion or phlebotomy dependent, the burden is even higher.
In a recent segment of Answers Now: Facing MPNs, Dr. John Mascarenhas, MD, professor at Icahn School of Medicine and director of the Adult Leukemia Program at Mount Sinai, joined us to offer advice and guidance to phlebotomy or transfusion-dependent MPN patients. He was accompanied by the host and patient advocate Ruth Fein as they covered commonly asked questions on precautions for immunocompromised patients during COVID.
This program is sponsored by Incyte and is produced in partnership with the MPNRF. These organizations have no editorial control. It is produced by Patient Power. Patient Power is solely responsible for program content.
Transcript | Advice for Transfusion-Dependent MPN Patients During COVID
Ruth Fein: The tricky and stressful thing for so many of you who joined us today is what to do or continue to do and not to do, during this pandemic. And we'll get right to that discussion with Dr. Mascarenhas.
Are Phlebotomy or Transfusion Dependent Patients at a Higher Risk of Contracting COVID-19, or Increased Risk for COVID Complications?
Let's start with what we've learned about COVID and MPN patients. Are there increased risks of contracting the virus, and are we at greater risk for complications if we do get it?
Dr. Mascarenhas: So I'll start off by saying that, unfortunately, we still don't have that much information at our hands in terms of what to expect with MPN patients and COVID specifically. We have a lot of information that's generalized from studies they've done retrospectively looking at patients with cancers and their outcomes, and we know that patients with cancer tend to do worse than patients who don't have cancer with COVID, in terms of complications. And some of it is intimately involved with the age of the patient. So patients who are older tend to have more problems than patients who are younger, and those problems center around usually lung issues, inflammation of the lung that leads to pulmonary failure and even clotting that can occur, that can also contribute to multiple organ failure. There's still a lot about this disease and the process that we don't totally understand.
So, we're still learning actually, about what makes this distinct from other viruses that are well known to the community like influenza. It seems to be easily transmittable, and when patients are infected, there's a spectrum of scenarios from being totally asymptomatic, to having low-grade symptoms, to being very sick. And it's obviously the very sick patients that we're concentrating on to figure out why do they behave that way, and what can we do to meaningfully intervene. With patients with MPNs, we initially had a concern, many of us in the community, that because it's an inflammatory state, particularly myelofibrosis, that they may be at a heightened risk for having complications from COVID, which appears to really stimulate a very hyper-inflammatory state in the host. And it's that inflammatory surge or cytokine surge that they call it, that seems to lead to a lot of the complications, again, in the pulmonary and thrombotic or clotting complications.
So, a grouped mainly from Italy led by Dr. Barbui did a study of about 37 centers throughout Europe, it was about 180 patients with MPNs. And this was retrospectively, looking back at their outcomes. This included patients with ET, PV, and myelofibrosis, and even some patients with pre-fibrotic form of myelofibrosis. And what he saw was that patients who had these diagnoses, many of them didn't do well. And I'll explain to you why I take this data with a grain of salt, but many of them didn't do well because they ran into the complications of pulmonary issues. And that the mortality rate or the fatality rate was high, particularly in patients with ET who had thrombotic complications. Now, the problem with this study, and it's not the problem with the investigator, Dr. Barbui is excellent, but the problem with the study is it's a few number of patients and it's highly biased because it was mostly patients who were picked up in the hospital setting.
And these tended to be patients who were sicker by nature because they were in the hospital. And most of the patients, or a good majority of the patients, were older in age. And we know that patients who are older, in advance of 60 or 70 years of age, tend to have more complications at a higher rate than patients who are younger. And MPNs are disease primarily of older people, but not exclusively. So there's still a lot to be learned. And I personally can't draw too many strong conclusions off of that early work by Dr. Barbui, but it continues to grow and continues to accumulate more data to get more information. I do not think that patients with MPN are more susceptible to COVID, I think that's really important for the audience to note. You are as susceptible as anyone else is out in the community.
What Are Your Thoughts on Receiving Treatment in a Cancer Center Right Now?
Ruth Fein: I'm going to start moving into some of the questions we've received. One is a great question. And that is, are there other options for people who are dependent on transfusions or phlebotomies? Is it something that can be done in a home setting, is it at all possible if they aren't comfortable going to a location? They might have to take public transportation or for some other reason?
Dr. Mascarenhas: Yeah. I want to reiterate that the chances of catching COVID in a cancer center is actually very low. And I'll tell you why, because 99.9% of the people, if not a hundred percent of the people in the care of patients with cancer in the cancer centers, are using those precautions, our masks and gloves. So I think that the chances of catching it within a cancer center are actually quite low, but the reality and the fear of the mass transit part of it is real. And just out and about, I can appreciate that aspect. There isn't a safe way, and this comes up a lot, it's a great question.
There's no safe way, and because there's no regulated way to provide a transfusion at home. That makes it difficult. Nor are we able to, for example, prescribe a transfusion. If you live in Saratoga, I cannot prescribe a transfusion at the local hospital or infusion suite there, it has to be done by someone on staff. So unfortunately, providers can only provide transfusions at places where they have privileges and admission rights. So that makes it challenging for patients.
Is It Possible for an MPN Patient to Contract COVID-19 through a Transfusion?
Ruth Fein: Is it possible for an MPN patient to catch COVID-19 through a transfusion? And if so, what can the blood banks do to prevent that from happening?
Dr. Mascarenhas: So, early on in the pandemic, that was one of our concerns, because we transfuse so many patients and we were very concerned because we didn't know enough about the disease, whether that might be a mode of transmission. It turns out that that does not appear to be a mode of transmission, the virus is really transmitted through particles in the air, from sneezing or talking or coughing, that then get into the mucus membranes and the nasal passages or the mouth. And that's really the mode of transmission. So it does not appear that you can transmit it through the blood, and investigators have looked at this and that's not been a concern. So, we can transfuse people safely without worrying, unlike hepatitis C or other viruses, and HIV, that proceeded this, you're not going to get it from a transfusion.
I do see a light at the end of this tunnel. I think that the way we treat patients right now, even in the absence of a vaccine, has improved outcomes. And what I mean by that is, simply the approach to the normal standard of care of oxygenation, anticoagulation, and steroids, plus or minus remdesivir (Veklury), the antiviral that got an approval for use in this area, has dramatically changed what I see in terms of the trajectory of patients today coming in with COVID. The rate and the number of patients that end up in the ICUs is much less than it was during the height of the pandemic.
It became clear that COVID stimulated this hyperinflammatory response in patients, and that was what was leading to the complication rates. And we know that JAK inhibitors are potent anti-inflammatories, so it didn't take much thought after that to wonder would JAK inhibitors be useful in this setting. And the Chinese were really the first to evaluate in a phase two study the effects of ruxolitinib (Jakafi) in patients with COVID, and it's a small study, but what they showed was that the duration of hospitalization was shorter in patients who got ruxolitinib than patients who didn't get ruxolitinib.
Which would suggest that patients weren't getting as sick and they could go home sooner. Because of that, now there are many multiple studies, large studies, ongoing, evaluating both ruxolitinib and other JAK inhibitors. We have a study in which I'm sharing throughout the country, which is a study looking at pacritinib, which is a JAK2 inhibitor that's in advanced testing for myelofibrosis, for patients with low platelets. And it's a very potent inhibitor of inflammation, particularly the IL-1 beta signaling pathway, as well, as it turns out, it has antiviral properties. So it is very well-poised for the treatment of COVID. And this is a study randomizing patients with COVID, whether you have an MPN or not, to 14 days of pacritinib, versus placebo, and everyone gets standard of care.
I'm hoping that we'll have some signal of whether this is panning out by the end of this year, but I find it a very attractive and very promising way of treating patients with COVID. And of course, if you have MPN and you are on Jakafi ruxolitinib, and that's one of the questions Dr. Barbui is looking at in his cohort of patients he's following is, does ruxolitinib afford you a benefit? Are you less likely to get very sick from the disease? Because the drug does dampen that inflammatory response to the virus. And we don't have a good answer to that yet, but emerging data would suggest that may be the case.
What Are Your Thoughts on Potential Side Effects of a COVID Vaccine in MPN Patients?
Ruth Fein: Are you worried about potential side effects from a vaccine for people with an MPN? And what about specifically for people dependent on transfusion or phlebotomy?
Dr. Mascarenhas: There's live vaccines and dead vaccines. So live vaccines, we discourage MPN patients from taking, any patient with a myeloid malignancy. Dead vaccines shouldn't cause a problem necessarily for an MPN patient. I guess the theoretical concern would be if the body were to develop a robust immune response to the vaccine, could it manifest as a hyper-inflammatory state in a patient with myelofibrosis? That's a theoretical concern, but I don't know that we know that yet. Unfortunately, we still have a lot to learn about this. I don't have a firm answer on that.
The only possible scenario where I would have some reservation and hesitation would be a vaccine that would induce a very potent and robust immune response very quickly to the COVID-19 virus particle. That could be problematic to someone with myelofibrosis, one could envision. But I think it's premature, very premature to draw a conclusion on that.
Why is the Flu Shot Important for MPN Patients During COVID?
Ruth Fein: How important is getting a flu shot this year? And is it more important with COVID, is it the same, what do we know about that?
Dr. Mascarenhas: Yeah, I would strongly recommend a flu shot this year, particularly because you don't want any reason to have a compromise of your pulmonary system during the height of a pandemic, even with another virus like coronavirus. And we haven't seen this, or I don't know of enough data yet, one could conceivably have both flu and coronavirus, which would be very scary. But what you don't want to do is leave yourself vulnerable by picking up the flu, because then if you were, God forbid, to get COVID, that you'd be at a worse starting place than someone who didn't have the flu. So I am definitely a strong advocate for making sure you get the flu shot. Here in our hospital, all the employees and faculty got the flu shot immediately when it was available, and we've been advocating it for our patients. I think pneumonia shot, which is usually given every three to five years, should be kept up to date as well for the same reasons.
It has definitely affected accrual enrollment around the world, we're still seeing that and the ramifications of that. We've lost patients on study who couldn't stay on study. The momentum for some of the studies has been slow because of result of it. And that's understandable, I think it'll eventually pick up. And one thing I've been proud about is that both the physician community, the academic community, the pharmaceutical community, and the government, the regulatory bodies came together and really figured this one out quickly. How to help make sure that patients remain safe and have access to studies during this pandemic.
And myself and many of my colleagues are still able to enroll patients, and as you pointed out, some of the criteria have become a little bit more lax. Some of the things that we can do on study are a little bit more dynamic than we were able to do prior to the pandemic. And I think those things will last, so even when the pandemic ends and it will end to some extent, I think that some of those things like the telehealth visits will persist. I think the government and insurance plans, they all have to figure out what that's going to look like, but I do think that we will have positive reminders of this pandemic that will persist.
Can You Share Information on Current MPN Clinical Trials Related to COVID?
Ruth Fein: Tell us a little bit more about your own study. Is there something more that you'd like to share with us on why you're hopeful about that?
Dr. Mascarenhas: Well, the PREVENT study is a randomized phase three study of pacritinib, which is an oral JAK2 inhibitor that has been tested extensively in myelofibrosis. And it particularly looks promising in patients with low platelets in myelofibrosis. And the PACIFICA study is an ongoing study that I'm sharing that is for myelofibrosis patients with low platelets that need a JAK inhibitor. But the PREVENT study is a study of patients with COVID, whether they're MPN patients or not. And it's a study that's randomized to the study drug pacritinib, or placebo, and it's double-blinded so we don't know who gets the drug and the patients don't know. And the goal of the study is to see if pacritinib, this oral drug that's taken twice a day, will reduce the inflammatory consequences of COVID and therefore make it less likely these patients who are infected end up on a respirator, or God forbid even worse.
And based on the mechanism of this drug and what we know about this drug, it should be very active actually in this setting, because of its anti-inflammatory and antiviral properties. So I've been very excited about this study, and I'm hoping that it will have a meaningful impact on patients with COVID, whether they have MPN or not. But patients on Jakafi right now, on commercial Jakafi or in your case, patients who are taking Jakafi in the context of a clinical trial, I do think probably, maybe not in every case but in most cases, are probably at an advantage in terms of the consequences of COVID.
And like yourself, I've had a number of anecdotal, and they are anecdotal cases, of patients who got COVID, unfortunately, in the height of the pandemic, who I would have absolutely thought would have done much worse and who did very well. So I was very encouraged by that. And of course, I never draw a firm conclusion off of an antidote, you really need the perspective controlled studies, but I'm looking forward to, and I'm optimistic that they will be very helpful in helping us help everyone through this pandemic.