Transcription:

Dr. John Leonard (Host):  Welcome to Weill Cornell Medicine CancerCast, conversations about new developments in medicine, cancer care and research. I'm your host, Dr. John Leonard. And today we will be talking about COVID-19 vaccines and cancer patients. As the coronavirus vaccine rolls out around the country, I'm really excited to introduce today's guest, Dr. Kristen Marks, who's an Infectious Disease expert at Weill Cornell Medicine and New York Presbyterian Hospital. Dr. Marks conducts research on HIV, hepatitis virus and COVID prevention and treatment. When the COVID pandemic hit New York City, Dr. Marks led the phase 3 trials of Remdesivir at Weill Cornell, as well as the phase 3 Moderna Vaccine Clinical Trial. So, she's really a great person to give us the latest on where things stand in COVID vaccination and COVID therapy.

I want to remind our audience that we are recording on December 21st, 2020. And therefore, if you're listening to this at a later date given the nature of COVID vaccine and COVID treatment information, things may change by the time you're hearing this podcast, particularly if you are hearing it a few weeks into the future. So, please be sure to look into any new data that's come in the interim time period from which we recorded this podcast. That being said, it's really great to have you here, Dr. Marks. Thank you for joining us. You're really an expert in this field, and we're lucky to have your insights into this area.

So, I want to start just asking you how you ended up working in infectious disease research and clinical care. This has certainly become quite a busy area for our country, for our patients, for you personally, no doubt, over recent months. How did you end up working in this area as your career focus?

Kristen Marks, MD (Guest): I'll say it was originally virology that drew me to medicine at all. I was very interested in biology and became interested in viruses, particularly in college. That interest and particularly in the HIV virus, which at that time had little in the way of therapeutics you know, motivated me to want to learn more and go to medical school and ultimately do the training needed to become an infectious diseases doctor. started my work on HIV and hepatitis in residency. And that was a time when HIV treatments were better, but there was really, again, very little offer for hepatitis C. I've had the good fortune of seeing treatments for both of those diseases evolve so that we can give people a pill a day for HIV, most of our patients who are newly diagnosed and for hepatitis we actually have curative therapy. With SARS COV2, I'd say I got involved because of my interest and knowledge of antiviral clinical trials. And I hope that soon I'll be able to say the same thing that we can cure or at least prevent any disease progression before people get sick from SARS COV2. We're not there yet.

Host: Well, thank you so much for your work. You've been very crucial to our efforts at Weill Cornell and New York Presbyterian in treating patients who are dealing with this virus and have also been, a leader, not only locally, but nationally in the vaccine approaches to this and getting them out and testing them in patients to see their efficacy.

And we'll come back to the treatment a little bit at the end because that's also changing and I'm interested to hear what's new from your perspective. But I think what everybody wants to hear about now is really where things stand with vaccination. And so, now as of late December, 2020, we, will soon have, two vaccines available, these vaccines are different than some of the prior vaccines that people are used to as they'd gone through their childhood and vaccinations and their flu shots. What is special about this type of vaccination as far as how they're made and how they work?

Dr. Marks: Yeah, so there the two vaccines that you're referring to are both MRNA vaccines, and they were both approved for emergency use authorization. So, that's different than FDA approval. I just want to be clear that these are not yet FDA approved, but because of the state of the pandemic, the FDA determined that the benefits far outweigh the risks and I'll tell you more about the potential side effects of the vaccines as we go on. what's different about these two, I'd say they're different, but they're the same. So, in general, with vaccination, we tried to give the immune system a part of a virus, sometimes even the entire virus, but in this case, a part of a virus to recognize and to use to make an immune response, to protect the person for when they actually truly encounter the virus.

So, in the case of these vaccines, utilize a technology called MRNA. So MRNA is something our body naturally makes. And it's kind of the, I'd say recipe for making proteins. It's the code that our body uses how they're used in vaccines is instead of this MRNA code is for the viral protein, the spike protein.

So, just one tiny part of the virus. It does not include the virus itself and there's no way to get COVID from these vaccines. So, that's you know, exciting part about them. They're not live vaccines, they're just utilizing a part of the virus that can't cause infection. So, with the case of MRNA, you injected into someone's arm. I should say the MRNA is wrapped in a little bit of sort of lipids or fat to protect it from being degraded. So, it has to have something around it to help it get into the cell.

When it gets into the cell, it stays in the cytoplasm of the cell. So, it never enters the nucleus where our genetic material is. It uses the cells own structures to make a protein that it can then kind of present to the immune system and allow an immune response. We know there's an antibody response and also in the early studies, it looks like there's a T-cell response too. so in that way, the immune system now is sort of tricked into thinking it has seen the virus. So, the next time, if someone actually encounters it, it can fight it off and hopefully prevent infection altogether. And in addition, prevent more severe symptoms from the infection.

Host: I want to ask you in a minute about the efficacy that was demonstrated in the clinical trials. But you alluded to the fact that they're more similar than, than different. Any key differences that people need to know about? it sounds to me like basically they seem to be in the same ballpark as to what to expect out of them and when they're available they should be more or less similarly used. at this point, is that more or less how you would put it as well?

Dr. Marks: Yes. as of right now, we don't know of any potential benefit of one over the other. So, the two that have been approved are the Pfizer BioEnTech and then the Moderna vaccines, both are the MRNA vaccines. again, they've been approved for emergency use. So the Pfizer BioEnTech vaccine is given in two doses, 21 days apart. Whereas the Moderna vaccine is 28 days apart. So, you would expect to have an immune response a little bit, you know, on the order of days sooner with the Pfizer BioEnTech vaccine. The other main difference is sort of how they're stored. So the Pfizer BioEnTech, as you've probably heard on the news requires this ultra cold freezers or dry ice for storage, which can make it a little more difficult to use on sites that don't have those special freezers. The other difference that's been observed so far is there have been a few isolated allergic reactions to the Pfizer BioEnTech vaccine.

And we don't know yet if Moderna poses the same risk. This is something we're prepared for with all vaccines. And there is guidance about, you know, people who've had severe allergies or allergic reactions to vaccines or other injectable medications to take special precaution.

Host: So the main side effects that sounds to me are focused and we'll get to efficacy in a second, but it sounds like the main side effects seem to be kind of injection site reactions and maybe occasional fevers and things of that nature, and then these occasional allergic reactions is that, is that the basic things that people have to think about?

Dr. Marks: Yes. I'd say it's very similar if people are familiar with the Shingrix vaccine. So, anyone who's received that, I'd say the side effects are on the order of that vaccine. So, in general, when the immune system is responding, some people, not all people will get body aches, which we call myalgias, sometimes fever, even headaches, a little bit of fatigue, sort of feel fluish. Although, you know, again, they don't have an actual infection, but their immune system is being tricked into thinking that there could be a virus around. So, it's responding in that order. The fever is pretty rare after the first injection, but a little bit more common after the second injection.

It usually is gone by two days, but some people can have it linger a little longer. I think, you know, one of the things people will have to work out is when COVID is circulating anyone who gets a fever has concern about, you know, are they contagious? Do they have COVID? And in general, if the fever goes away in the first day or two, you probably don't need to be concerned about   what is going on. But if it lingers that's when I would recommend people have a usual evaluation for fever, it still may very well be the vaccine. But you want to at least rule out that you had been exposed to COVID before getting the vaccine.

Host: So, Efficacy wise, I've looked at some of the studies and I'm sure others have heard about them and you hear these things like 95% effective or things of that nature, but obviously those are, kind of complicated analyses, how should a patient think about it? If they're vaccinated, kind of what level of protection they're getting or how would you put it for people to kind of get a feel for how protective this is for an individual or a group of people,

Dr. Marks: So, the studies were designed to really look at, did it prevent symptomatic infection? So, I kind of want to stress that point first. So, the data we have is actually the prevention of people getting sick. We don't know yet as much about preventing asymptomatic infection, although, you know, I'm hopeful, it will also prevent those infections.

So, in terms of people getting sick if you look at the Pfizer vaccine over the course of just the first few months of the study, they had 170 infections of which

eight were in the people who got the vaccine, the 162 in the placebo. So I think, you know, when you think of those numbers, that's a pretty dramatic decrease in symptomatic infection and if you talk about it in terms of efficacy, that's a 95% efficacy.

And also importantly, it nearly eliminated the severe infection. So, infections that required people to need oxygen or be hospitalized. And in the Moderna study, there were quite a few of the severe infections. There were 30 severe infections, nine of which were people who needed to be hospitalized. And there was even one death. All of those occurred in people who received placebo, no one in the vaccine arm had severe infections to date. Now that number may change as you know, as we get more data on these studies. Again, this data that we're looking at is just after the first few months, but it was enough to prove that the vaccine is very effective.

Host: And so one thing people ask about is how the timeframe has obviously, and I think in a good way, been short in that we've got answers quickly, that we've seen benefits from these vaccines and in a relatively short period of time. On the flip side, we don't have a lot of long-term follow-up clearly. Are there any particular thoughts you have about that? I mean, obviously we don't know, but if you had to look at the longer-term questions either as far as risks, or as far as how long this immunity is expected, or we're just going to have to await those data, any, any guidance or at least ideas recognizing that nobody knows for sure kind of the longer-term view with these?

Dr. Marks: So, in terms of risks, you know, you have to think about it while also considering benefits. So, we know from these very large studies, there were no serious events that were attributed to the vaccine. And if there are going to be side effects from a vaccine, they usually happen within the first 42 days. So, that's why the FDA took kind of a looking at data from people who had been out at least two months from the vaccine to kind of collect that information. To see very rare side effects, it takes hundreds of thousands of people. And often those aren't detected until the vaccines are released.

And I think the example of the possible allergic reactions to the Pfizer BioEnTech vaccine is a good example of that. So, there are surveillance systems to pick these up. They're looked at actually weekly and then the data's forwarded to the FDA monthly. So, safety analyses are ongoing, but being, concerned about an extremely rare side effect it's important and it's important to capture what those are, but it shouldn't prevent people from getting the vaccine now, because we know the risk of COVID right now is so high. So, the benefits of the vaccine, you know, far outweigh the risks that could be associated with getting COVID.

Host: So many of those in our audience are either patients with cancer or loved ones of patients with cancer and obviously for many scenarios, patients with cancer are different from the standpoint of both the risks that any treatment or potentially a vaccine would have in a cancer patient, as well as their immune systems may be different depending on their situation. And perhaps the vaccine either will work or perhaps might be less effective. So, from the standpoint of safety in patients with cancer and efficacy in patients with cancer, any thoughts you have? And I think, you know, I'll caution the audience, it's really hard to generalize because there are many, many different individual situations, but in a general sense, any either concerns patients with cancer should generally have about safety or efficacy, if they have the opportunity to receive one of these vaccines in the near future?

Dr. Marks: So, in the near future it's recommended that people who have cancer or are immunocompromised can take the vaccines that I've discussed. And that's because they're not live vaccines, so there's not a concern for necessarily any additional safety risk from receiving them. We don't have data on how well they will work. And I think, again, that'll probably depend, like you said, on what type of cancers people have, what's their current treatment for those cancers. And I think we need that data to understand. We also don't have sort of a surrogate for knowing someone's been protected. So, I think once we know what antibody titer you need or what measure it is exactly that, you know, we can feel people are immune, people who get this vaccine should really continue to use the precautions of wearing a mask and social distancing.

And I'd say that's especially true for immunocompromised people who may not mount as good of a response to the vaccines. So, I feel pretty comfortable telling people who aren't acutely ill, I mean, I think if you're, you know, very ill with your cancer at the moment, it might not be the right time to get the vaccine.

As we said, the vaccine can cause fever and some other side effects and you have to be able to tolerate those sorts of things. I think also the physicians and care team treating you may also decide there might be sort of within your treatment an optimal time to take the vaccine, to try to have the best chance of responding to it. And I think that's another consideration is sort of when to give it, trying to finesse the timing a little bit to help you have the best response.

Host: Yeah, I would say from my own experience, we do have some people where we've either paused their treatment or kind of put off their treatment a little bit in the hopes that they can get vaccinated, have a good response to it, and then resume their treatment for their cancer. On the other hand, clearly, we don't want to compromise someone's cancer therapy for this purpose if we don't have to. We don't want to put people at greater risk for having complications and problems from their cancer while we're I don't want to say theoretically, but at least partially holding out the vaccination as an alternative or as an important complimentary treatment.

So it can be tricky. And I would just encourage people to speak with their doctors about their own individual situation to try to navigate this as more information comes along. The other question I wanted to ask you around the benefits or potential benefits of the vaccine is this issue of protecting transmission of infection, the idea that if I am vaccinated that the vaccine would not only prevent me from getting ill from COVID, but also potentially prevent me from transmitting COVID. Is that something that we know much about at this point in time? Or what are the initial thoughts around that?

Dr. Marks: We don't know as much as we'd like to, but we do know some things So,

In terms of preventing asymptomatic infections, we have a small amount of data from the Moderna clinical trial in that study. All patients who were getting vaccinated, how a swab done at the time of the vaccine to determine if they had an asymptomatic infection.

In between the two shots. So at the time point where they entered the study and got their first shot and came in and got their second shot, some people unknowingly picked up the SARS COV2 virus, but remained asymptomatic. And what was seen was that that happened two thirds, less frequently in people who got the vaccine.

So it appears that the vaccine may protect from asymptomatic infections. We need a lot more data to be able to confirm that, but it's a very encouraging sign.

Host: It seems to me that that's good news for a lot of reasons, obviously less transmission, but also perhaps for cancer patients, if ultimately their families are also getting vaccinated and the people they come in contact with potentially, that will reduce the transmission and their kind of secondary risk beyond whatever protection they might get from being vaccinated themselves.

Again, all of that's not clearly established, but at least it sounds encouraging that that might in fact be the case.

Dr. Marks: Yes. I think that's a great point. And I think people with vaccinations in general, people with, family members of patients going undergoing cancer treatment should be encouraged to get vaccinated, to help prevent transmission of infections to the patients themselves.

Host: So You've led a number of clinical trials in COVID and in the vaccines, I mean, how, particularly in the vaccines, this must have been very exciting. You must have had lot of people interested in this area and participating. Any kind of reactions that how it's been to be taking part in such an important area? We're, big supporters of clinical trials at Weill Cornell and have a lot of them going on, but this group of trial seems to have even greater importance to our society, given the timing and the severity of what's been going on in the world.

Dr. Marks: I've been blown away by the willingness of people to volunteer for these studies. We've literally had people knocking down our doors, wanting to be in this study with, what I would say are very selfless reasons of wanting to do something for the community, to ensure representation of diverse populations in the studies. It's really been humbling and really inspiring. So, yeah, I feel lucky to have been involved in these.

Host: We owe you and your colleagues a great debt in getting this forward. I know it's a lot of work to get clinical trials open. And of course, most importantly, the individuals that have participated in them and been willing to go through the process has been really great and something we should really appreciate. So, I know that there are a number of other COVID vaccines in development. Any major take home points about them at this point in time? I know a big part of this is just kind of increasing the flow and the availability of vaccines as we have multiple vaccines available, obviously, it'll help give access to more and more people across the country, across the world.

But there are others, as I understand it. Any big takes as to how they might be different or similar or just any impressions of those that they come along, recognizing that in the coming months presumably additional options will be available.

Dr. Marks: Most of the ones that are furthest along in development, still focus on that spike protein, but they have different ways of delivering it to the immune system. So there's viral based vaccines that actually use a virus to deliver the protein. There are kind of what I would say are the more traditional vaccines where you give the protein itself, along with an adjuvant, which is something that helps stimulate the immune system, sort of like a booster.

We are actually going to be soon starting the Novavax vaccine study, which is one of those protein-based vaccines that gives a protein and adjuvant. So, I do think, there may be differences in how different populations, including cancer patients respond to different types of vaccines. So, I think it's great to have different options. I probably, for people who are immunocompromised would avoid the viral based strategy, but I think the protein vaccines will be a good option.

Host: So, one big question that every patient and non-patient has, I think. Hopefully most people are excited to have access to a vaccine. Obviously, there are people that are hesitant for various reasons, but I think you've given us lot of reason to encourage and embrace getting a vaccine given the potential benefits. But the timeline seems to be taking some time, and these are complicated reasons and certainly this is rapidly evolving. But people read on the news and the newspaper, hear on the news about these different discussions around tiers and timing of when certain categories of patients will have access to the vaccine.

And I don't want to ask you your thoughts on, how it should be or how it will be, because this is going to be rapidly changing in the coming weeks and so on, but maybe just give people a sense of how those that are making these decisions, are they thinking about how to roll out these vaccines while the supply is limited until we have more available for the general public?

Dr. Marks: First of all, I just want to say people should remember, usually it takes years to get a vaccine through all the steps we need to know whether it's safe and effective. So, this timeline has been accelerated, but no were skipped. They were overlapped. So, production of the vaccines started before we even knew if they worked. And that's why we have as much vaccine as we do already. in a normal situation that would never happen. So, I think I should be very encouraged about where we are with all this. And I think the efficacy, particularly, it's pretty staggering how well it works. So, I want people to be optimistic and excited to get the vaccine. The timing can be stressful because I know everyone wants it yesterday, including me. I still haven't gotten access to the vaccine yet. So I'm, right there with everyone else.

Host: I agree as well.

Dr. Marks: So, hopefully that'll change in the coming weeks. what has happened is the CDC and other groups as well, have thought lot about how to prioritize, how to roll out the vaccine. So, eventually everyone will be offered vaccine or certainly everyone 16 and older under these EUAS. They notably are not yet approved for people under 16. So that's a group that, won't be recommended vaccine in the near future until we have data on children.

But the rest of us, how things are being rolled out is sort of where the is thought to be maximal. So for healthcare workers, we need healthy nurses and physicians and other healthcare professionals to there to take care of sick people. So, that's why they were given the priority. Nursing homes obviously have been devastated by COVID. And so they were also in the early phases of rollout, nursing homes and long-term care facilities. so the CDC has also, the later tiers, including essential workers, people with co-morbidities, people 75 and older, 65 and older there's plan in place.

And based on people's local, state needs, the state can make adjustments for it. If there's certain reasons they may need to prioritize one population over another. But the hope is that vaccine scale up will continue. That's the main benefit of the RNA vaccines is that they can be made quickly. And that eventually everyone will have access. So, I'm hopeful that by spring we'll be in a very different place in terms of access to vaccine, but we'll wait and see.

Right. Great. Well, before we finish, I just wanted to ask you, I know you've been involved with taking care of patients with COVID-related disease and helped as we mentioned to develop the therapeutics that we have. Are there any new treatments that are coming along and maybe that you're excited about and clinical trials beyond standard things, which we're doing in the care of patients thoughts about where treatment is going what's exciting there?

Dr. Marks: Well, before I get to treatment, I just wanted to mention monoclonal antibodies which were approved for emergency use for treatment. But I think in cancer patients, they could also have a role in prevention. These are manmade versions of antibodies that can protect against the virus infection. And so those are being studied right now to see if they actually can prevent SARS COV2. And I think if they are found to be effective in prevention, that could be a very good option for someone undergoing cancer treatment so that they could get that and then, eventually when their own immune system is working better, get the vaccine. So, its kind of as a bridge to vaccination.

Host: So, the concept being much as some of our patients receive gamma globulin to prevent infections, patients could potentially receive several months of an antibody-based prophylactic while their immune system is low. And then later get vaccinated, that's something that you envision potentially, and I want to emphasize potentially might be useful for some situations in the future.

Dr. Marks: Yes. I think that is a strategy. If it works, would be a very useful strategy. And then terms of treatments the COVID illness we think of it into sort of two main parts. So, the early part of it is when the virus is reproducing a lot of virus around and then it's sort of the immune system kicks in and then the immune system starts to do the damage in terms of causing excess inflammation or inflammation, that becomes destructive to a person's body. So, both parts of that are being targeted for treatment. Right now we only have intravenous antivirals to use, so they require people being admitted to the hospital. There are some studies going on, of trying to use those as outpatients. But I think antivirals is certainly an area where we need better drugs, oral drugs, or something that can be, easy to administer as an outpatient before people require hospitalization. And then in terms of once people are hospitalized and suffering the consequences of an overactive immune response, different immunomodulators. So, things to kind of dampen down the immune response are being studied. So, both of those are ongoing. We have trials at Cornell of the treatment with monoclonal antibodies, of treatment with convalescent plasma and of treatment with immunomodulators. There's also studies looking at whether anticoagulating people's blood or sort of giving them medications to prevent blood clots, whether that is a benefit, because we know there's a lot of clotting and strokes and heart attacks and things that can be, consequences of severe COVID. So, there's a lot of exciting research going on at Cornell and throughout the country.

Host: So before we wrap up, any key messages that you would really want cancer patients and their loved ones keep top of mind, as we move forward here into this new era of dealing with the Coronavirus pandemic Any words of advice, as people try to hang in there through all this?

Dr. Marks: I would just recommend people get their information from reliable sources. So, podcasts like yours, New York Presbyterian has information available about COVID. There's just so much misinformation circulating. You really want to get information on COVID and prevention and the vaccine, particularly from healthcare professionals.

Host: Great. And keep wearing your mask and washing your hands and keep distancing. And hopefully before too long, much of this will be behind us.

Dr. Marks: Absolutely. I just want everybody to have a safe holiday season so that, all of your family is around for the next holiday season when we're hopefully in a much different situation.

Host: That's a great way to think about it. I've told patients many times, you know, yes, may be in the hospital or sick, or going through treatment or discomfort, or challenges in the short term, but the goal is to be around for many more holidays to come. So, Dr. Marks, I want to thank you for joining us. This has been a great update, really informative for everyone. I want to thank you for all the work you've done for our patients and our community across the country. It's really made a big difference and we really appreciate all your efforts.

I want to invite our audience to download subscribe, rate, and review CancerCast on Apple Podcasts, Google Play Music or This email address is being protected from spambots. You need JavaScript enabled to view it.. We also encourage you to write to us@This email address is being protected from spambots. You need JavaScript enabled to view it. with questions, comments, and topics you'd like to see us cover more in-depth in the future. That's all for CancerCast, conversations about new developments in medicine, cancer care and research. I'm Dr. John Leonard. Thanks for tuning in