Full Show: COVID-19 and What Multiple Myeloma Patients Need to Know
Joshua Richter, MD
Tisch Cancer Institute, Mount Sinai
Interview Date: March 20, 2020
Thanks to our episode sponsor
The coronavirus is on the minds of global citizens and all myeloma patients. Dr. Joshua Richter shares an incredible amount of information for myeloma patients to navigate their care in these uncertain times. He shares drugs patients may want to ask their doctors about, considerations for stem cell transplant, the status of some myeloma clinical trials, tradeoffs of using IVIG, and potential therapies being used to treat the coronavirus. This is a must-read show to learn how the coronavirus is affecting myeloma patients and how they can be prepared.
Dr. Richter on Myeloma Crowd Radio
Jenny: Welcome to today’s episode of Myeloma Crowd Radio, a show that connects patients with myeloma researchers. I’m your host, Jenny Ahlstrom, and we’d like to thank our episode sponsor, Bristol Myers Squibb, for their support of Myeloma Crowd Radio and for this particular program.
I think all eyes and ears are on the coronavirus, and many myeloma patients are being impacted by it for all aspects of their care. Dr. Joshua Richter is at Mt. Sinai in New York City, one of the epicenters of the US outbreak today. He’s very aware of how it’s impacting his myeloma patients and those around the country.
So Dr. Richter, welcome to the program.
Dr. Richter: Thank you so much for having me.
Jenny: Before we get started, let me just give a short introduction for you. We have a lot to talk about. Dr. Joshua Richter is Assistant Professor of Medicine at The Tisch Cancer Institute in Mt. Sinai, with the Icahn School of Medicine in the Multiple Myeloma Division. Dr. Richter previously practiced with the John Theurer Cancer Center at Hackensack University and at Rutgers.
Over the course of his career, Dr. Richter has led significant research on the development of new or novel multiple myeloma treatments including carfilzomib, selinexor, panobinostat, daratumumab, pomalidomide, isatuximab, and ixazomib. His research also includes immunotherapies, stem cell transplant, and optimal treatment strategies in multiple myeloma.
I think we’ll just jump right in to the show today because it’s such an important topic and relevant topic. What are you seeing or how are myeloma patients being impacted by this coronavirus and what considerations are you taking into account for just about everything?
Dr. Richter: Obviously, this is the most important question that we’re all dealing with. One of the things that I have to say is despite the concern that everyone has, the medical community and the myeloma community is banding together in ways that have never been done before to make sure that everyone gets the optimal care during these crazy times.
There are some broad things that we’re doing and much of what we’re doing is patient by patient. From a broad standpoint, we’re trying to limit “non-essential things” and that’s complicate for a myeloma patient, what’s essential and what’s not. Transplants, for one, are not always essential.
For a number of patients with newly diagnosed myeloma, we give induction therapy and then the plan is to go on to transplant, many people achieve a good remission with the induction and if we’re able to hold off on transplant right now, we are. The big reason is that transplant requires not only a several-week stay in the hospital, which may be more risky at this time but it also suppresses the immune system. We want to make sure that everyone’s immune system is as intact as it possibly can be during this time.
We also very much encourage social distancing as much as can be done and thankfully, in many places, the ability to order food and/or drugs and other supplies is available. In terms of day-to-day therapy, we’re trying to switch over as much as possible to oral therapies. So there a number of oral therapies that patients are very familiar with; drugs like Revlimid and pomalidomide, there’s some oral therapies that people may be less familiar with, drugs like ixazomib, selinexor, and panobinostat.
What we’re doing for many people is trying to utilize regimens that use oral drugs. This way, people don’t have to come in on a weekly or twice weekly basis to their offices and hospitals to get infusions. Ixazomib is a proteasome inhibitor, much like Velcade or carfilzomib. For many intents and purposes, it’s very similar to an oral version of Velcade. Many people that are receiving Velcade which were switching over to ixazomib or Ninlaro.
Panobinostat is another drug that it’s not as commonly used but an extremely efficacious drug and can actually resensitize to previous drugs. Meaning, if someone’s on Revlimid, and Revlimid stops working, you can add panobinostat and resensitize them.
In some cases, we might’ve added Velcade previously or daratumumab or carfilzomib. Now, we can add drugs like panobinostat to control the disease without needing multiple visits.
Selinexor is another amazing oral drug that was recently approved, but we know that we can combine it with other oral drugs including drugs like pomalidomide. We’re really trying to switch things over to oral as much as possible, and limit the number of blood tests that is needed because we still need to go out to a lab or a center or your hospital to get blood draws. Really spacing things out and having regular communications with patients including things like telemedicine.
A lot of places are embracing telemedicine to have video chats through our phones and our devices to talk to patients, to go over their symptoms, review plans of care, help manage as much as possible so that people don’t have to unnecessarily expose themselves to anything outside.
Jenny: Okay. That’s a lot for myeloma patients to take in. Let’s just break it down if you don’t mind to some specific things.
Dr. Richter: Sure. Of course.
Jenny: You mentioned testing and blood draws. If I’m going in let’s say monthly, and I guess it depends on how your myeloma is behaving. If you’re in remission status and you’re getting tested every three months, so what you’re saying is you could just push that out and maybe wait an extra month to get testing if your myeloma looks like it’s behaving appropriately.
Dr. Richter: Absolutely. I mean this is case-by-case and patients should definitely talk to their care teams, but your sentiment is 100% correct. For patients who you know, we do a lot of things at a routine for optimal strategy but if we’re checking things every one month, for many patients, we can switch to two or three or even beyond, so I completely agree with you.
Jenny: Then for patients who have may have increasing myeloma, what are you recommending for them in terms of testing or blood draws?
Dr. Richter: That’s a more complicated issue. There’s two types of progressions that we generally talk about in myeloma, biochemical and more aggressive (clinic). Biochemical is where we’re measuring the M-spike or the free light chains, and they’re just starting to come up, but people feel otherwise well.
I think in those scenarios, we’re trying to add oral drugs to compensate. If you’re on Revlimid and progressing, we can add Ninlaro, we can add panobinostat, we can add selinexor to help control that.
For people who are having more aggressive progression of disease there, kidneys are starting to feel the pressure or they’re more anemic, or their calcium is going up (clinical relapse), that’s where we have a more complicated decision. We still are having the availability of the clinic and all of its resources, and just continuing what we wouldn’t do otherwise but just take more precautions.
Jenny: Okay. Well, I want to jump in to a question, so I don’t forget it going forward because you talk about different options, and it’s probably better if we talk about it later but I don’t want to forget it.
You mentioned selinexor. Because it was just barely approved, there are a lot of doctors that don’t understand how to use it and how to mitigate the side effects that you have with selinexor and if they’re managed properly, it can be just fine. Do you want to review a little bit about that so that patients, as they go and talk to their doctors like, I may want to try this and the doctor doesn’t know how? I’ve had community doctors push back on patients and say I don’t know how to use this drug yet.
Dr. Richter: That’s a really critical question. Selinexor was originally approved July 3rd of last year. It was approved based on the STORM study. The STORM study looked at just giving selinexor and dexamethasone as pills with no other myeloma regimens. In order to achieve a high enough response rate to get the drug approved, the drug needed to be given twice a week at 80 milligrams.
However, it’s a little more toxic to give it that way, and it’s far better to give it once a week. But if you give it once a week, you have to mix it with another myeloma drug so that you get enough synergy and it works even better. This actually comes true from the BOSTON study which was just read out as positive a week or so ago. When we combine selinexor with Velcade in patients do amazingly well. Instead of giving 80 milligrams twice a week, you give 100 milligrams once a week.
Optimally, the drug is given once a week and the dosing is different depending upon which drug you give it with. You give it with daratumumab, carfilzomib, or Velcade, it’s 100 once a week. If you give it with pomalidomide, it’s probably 60 once a week. With Revlimid, it’s probably 60 as well. Sometimes, pomalidomide, you can put it up to 80 but 60 is probably the better dose.
The other thing to mitigate it is it’s far better to be proactive than reactive in terms of side effects. We find that if we’re very aggressive about preventing side effects, they happen in much fewer patients as opposed to dealing with nausea or other problems after they have it. We give a combination of medicines to prevent it, things that are a little bit out of the box. Varubi is a drug we use quite often which is similar to Emend which some people may take.
We give drugs like Zofran and steroids. Another one is Zyprexa or olanzapine which is originally marketed as an anti-psychotic drug but actually has a lot of great efficacy to prevent nausea and GI side effects. And again, these are all pills. What we are doing is giving people many prescriptions. Unfortunately, there becomes a pill burden in this case, but it’s a way to prevent symptoms and control the disease.
Jenny: The BOSTON study I know is using selinexor with Velcade and dexamethasone. Would you consider using Ninlaro in place of that? With selinexor and dexamethasone?
Dr. Richter: That’s a really great question. There’s not sufficient data that I’ve seen yet with Ninlaro but in the STOMP study, which combined selinexor with a whole bunch of other drugs. We have data with selinexor and Revlimid and selinexor and pomalidomide. The best data so far is an all oral combo with seli, it would be selinexor, pomalidomide, and dex, and really great data coming out of the STOMP study for that.
Jenny: Okay. That might be something doctors might feel more comfortable applying for temporary situations, so yeah, that’s a really unique approach. Same question for panobinostat, what do you combine that with if you’re thinking about using panobinostat?
Dr. Richter: That’s a great question. It’s a phenomenal question. Panobinostat was approved in about 2014-2015, and it was approved based on the PANORAMA study combining panobinostat with Velcade. There’ve been a number of smaller studies now giving it with drugs like carfilzomib and more recently, looking and combining it with IMiDs, Revlimid and pomalidomide.
We’ve actually, at our center, have been using these combos for quite some time with a lot of success. There are a few unique things you have to look out for to make these optimal. The main thing about panobinostat is in the original study, it was given two weeks in a row and one week off. We found that it caused a lot of GI issues, mostly diarrhea, but if you give it every other week, it’s actually tolerated way better.
I saw a patient yesterday who’s having progressive disease and I put him on Revlimid, panobinostat and dex. The panobinostat dosed every other week. He’s going to go locally for blood work and we’ll review it via video visit every two weeks to monitor things.
Because the drug actually resinsitizes, and we have data showing this, that if you become refractory to a drug like Revlimid or pomalidomide, panobinostat can actually resensitize the tumor and make those drugs useful again. Even if you’re refractory to some of these drugs, we can actually still recapture you with an all-oral regimen.
Jenny: Wow. This is just amazing because the creativity that you are using. I mean you’re already a myeloma specialist and we highlight all the time how patients need to go talk to a myeloma specialist to get their care crafted but in moments of distress and crisis that we’re having right now, it’s even more important.
You mentioned telemedicine. Can patients reach out to a new myeloma doctor? Let’s say they get their care locally and they have somebody helping them craft their treatment strategy that’s local that may not know that much about myeloma. Are there other telemedicine options to get a second opinion with somebody like you or how is that all working?
Dr. Richter: One hundred percent. I literally saw two patients yesterday that I’ve never met before. I saw them via telemedicine visit and when I got off the phone with them, I called their local doctor to discuss all the details and email them my notes. The reality is that much of what we do is reviewing charts and having conversations and a lot of this can be done via telemedicine, so we have new patient visits that are already set up that we’re converting them all to new patient visits unless there’s some outstanding reason.
There are select group of people who still need to come in. If they’re having severe complications and we need to give them aggressive medicine immediately. But if it’s for a second opinion, absolutely. Reach out to any of the major myeloma centers. Many of us are already set up for telemedicine. I’ve been doing it for a long time, happy to do that.
Jenny: We have a Myeloma Crowd directory as well on our website. If you go to myelomacrowd.org, under the Find tab, you’ll see a list of myeloma doctors. If anybody has trouble getting in touch with some of the doctors, please just email me at firstname.lastname@example.org and I’ll make sure that they get the message.
Let’s talk about that. You mentioned for people who still do have to come in - so people are coming in for infusion like daratumumab and carfilzomib or even Velcade or things like that. Do you want to talk about potential strategies patients could think about in terms of their timing and their locations and the frequency and all that in a little more detail?
Dr. Richter: Absolutely. I think drug by drug. Daratumumab luckily has a very long half-life. There’s a general step up. The way daratumumab works is not exactly like a normal chemo where you give more and it does more. As an antibody drug, think about it that every tumor cell has a lock and the daratumumab is the key. As you build up the levels in your blood, every lock has a key in it. By dumping more keys, you don’t necessarily make things better. This key is hanging out for a very long time.
What we’re doing for some people is accelerating things and really getting to a less frequent dosage sooner instead of once a week pushing it twice a week or even once a month. Again, many patients who are seeing a variety of different centers or go for second opinions, our general recommendation is that if there’s a drug that is commercially available, to get treated locally and we are more than happy to continue to work with all of the local doctors to ensure everything is going smoothly.
For elotuzumab, another IV drug, many people are still giving it the classic way from the original study which was ten milligrams per kilogram every week for eight weeks followed by the same dosage every two weeks. With more recent studies, we know that we can double the dosage and have the visit times. You can push it up to 20 milligrams per kilogram and give it once a month. This allows people to continue on effective drugs that get them less frequently.
Velcade, a lot of our Velcade were switching over to Ninlaro because it has very similar efficacy and it’s a very useful drug.
Carfilzomib, what we’re trying to do for patients who require that drug is many of the original protocols gave it twice weekly, we’re reducing that to once a week.
Jenny: I have seen a lot of the studies talking about once weekly carfilzomib dosing and lower side effect profile and things like that too, and just as efficacious. It seems like that would be a really great option.
Dr. Richter: Absolutely. Then we actually know that as you crank up to those, sometimes, you can get better responses. The recent ARROW study, when we compared the classic twice a week dosing at 27 versus once a week dosing at 70, the once a week dosing was actually superior. Again, in times like this, that combined with fewer visits to a doctor’s office is a very advantageous.
Jenny: We’re going to learn a lot using all these different and new combinations. Let’s talk about isatuximab as well. Isatuximab was just approved. It’s similar in the same class with daratumumab. What’s your opinion on the use of that?
Dr. Richter: Isatuximab is a phenomenal drug. In the lab, it appears to be slightly better. When we actually give it to patients, it’s hard to say - it’s very, very similar. One of the big advantages to isatuximab especially during this time has to do with that first dose. Many people who may be listening, they know that first dose of daratumumab can take eight to ten hours. The second dose can be six to eight hours.
Now, we do have a subcutaneous version of daratumumab that’s going to come along any day now, but we’re not there yet. The benefit of isatuximab is that those first couple of doses, instead of eight to ten hours, the first one is like four hours. Instead of the second one being six to eight, it’s more like two to three.
One of the great advantages right now is it’s tolerated very, very well. Very efficacious drug and reduces the amount of time you’re in a clinic.
Jenny: Interesting. For patients who you’re doing telemedicine with, you’re sending your doctor’s orders to their local doctor. I think a lot of patients sometimes don’t know that you can get a consult with a myeloma expert and you don’t have to get through treatment there necessarily. You don’t have to drive in to New York City and get treatments there. You can get treatment at home and you can do what you did with the other patient which is just craft the strategy, tell the local doctor what to give and how to give it. I think patients just need to be reminded of that.
Dr. Richter: One hundred percent. The one thing that I would add that we’re very much encouraging at Mt. Sinai is just as it’s always a good idea when you come to a physician’s visit to bring somebody else with you because you never pick up everything, for telemedicine visits, it’s no different. We’re very much encouraging that when we do the telemedicine visits, if there’s someone else in the house to listen then great, or to conferencing somebody else, because we know that in these stressful times, no one’s going to remember everything.
The same thing for regular appointments, having somebody else listening to the information is very much encouraged.
Jenny: I totally agree. There’s a lot that’s covered and it goes quickly and you don’t necessarily catch everything. You’re thinking about other things like not leaving your house. It’s crazy.
Let’s go back to stem cell transplant. You touched on it at the beginning about potentially delaying transplant for those people and maybe having a few more cycles of your induction therapy and kind of pushing it out. For those who have a planned transplant, that’s your strategy it sounds like. For those who are just finished with transplant or are high risk and really need transplant as one of their options, what do you suggest?
Dr. Richter: Again, this is really, at the end of the day, this is a patient-by-patient discussion which is what we’re doing with everyone. In general, even in the high-risk settings, it is still -- if you have an excellent response to induction, there’s still some people who question the role of transplant. I think that the two questions that we think of is one, do we already have stem cells? If you already have stem cells, the timing is a little bit more malleable.
If you don’t have stem cells, you have to make a few other decisions. I saw a lovely person the other day, telemedicine visit, receiving carfilzomib, pomalidomide, dexamethasone induction, amazingly well, want to hold off on collection right now.
We know that drugs like Revlimid, if you have too much of it, it makes it harder to collect stem cells. For this gentleman and many others, we’re dropping the Revlimid, continuing them on their Velcade or carfilzomib, or Ninlaro or carfilzomib, and just letting them remain in remission with regular blood work following them closely and so we figure out the optimal risk benefit to collect cells.
For transplant, for people who already have cells, same thing. If you already have stem cells and you’re on a regimen that’s working, we encourage people staying on that regimen and we know that this is not an unreasonable strategy. There’s an ongoing trial called the FORTE study, really great study. It’s three arms, and one arm, people with newly diagnosed myeloma, (carfilzomib, Cytoxan, dex, plus transplant); (carfilzomib, Revlimid, dex plus transplant); or (carfilzomib, Revlimid, dex, no transplant). They just stay on it for 12 cycles. In both cases, the KRd arms did better.
There’s definitely a hint that the people who have high risk do better with transplant but continuing on your induction for more than the four to six cycles, there’s nothing wrong with that. For many people, it may even optimize things for when they go to transplant. We’re really trying to avoid it unless it’s the only choice that really makes sense.
Jenny: We talked about the immunotherapy. Are there any other specific drug that you want to discuss in terms of administration or differences in administration during this time?
Dr. Richter: I mean I think the only other drug that we’re talking about very heavily is IVIG. For many people who have myeloma, they get multiple infections. One of the ways that we boost your immune system or increase your normal immune globulin level is to give a drug called IVIG or intravenous immunoglobulin.
There are some risks and benefits. The main benefit is of course that it helps protect against infections. One of the potential risks that if you’re getting it once a month, that’s an extra visit to the doctor. Again, we’re discussing this on a case-by-case basis and one of the ways we do this is measure your IgG and we know your history.
If you have an IgG level and that’s your immunoglobulin level that’s 200, which is extremely low, and when you’re off the IVIG, you wind up in the hospital with pneumonia, you need to continue IVIG. If your IgG level is normal, and you haven’t had an infection in two years, we’re going to hold that especially now that we’re getting in to some of the warmer months or some of the non-COVID infections like RSV and influenza are going to go down.
Jenny: Right. That makes a lot of sense. Okay. Can we talk about just weakened immune systems in general?
I know if patients are on a lot of myeloma therapy for a really long period of time, sometimes they can have a weakened immune system. Are there any drugs that patients should stay away from or what’s your opinion on that?
Dr. Richter: I mean I think that’s a really, really great question. Myeloma’s of course the hardest place to answer because myeloma itself, the bad cells weaken the immune system. When we give some our drugs, they may weaken them further. The quick and easy answer is it’s a case-by-case basis. But there are some strategies that we’re taking in some people who are on many different drugs.
Let’s say they’re on daratumumab, Revlimid, and dexamethasone and have been on that for a very prolonged time. We may stop the daratumumab literally to avoid them having to come in to the hospital, but the other benefit is that it does relax some of the pressure up the rest of the immune system, may give them a little bit of immune recovery. It’s a win-win for some patients for whom it’s clinically appropriate to back off on their therapy.
I think the best thing we can do is as case-by-case, really personalized medicine is really this, who needs to still be on the aggressive medicine? Who have we just kind of kept on aggressive medicine because that’s what seems to be the right thing, but now maybe suboptimal?
Jenny: Well, you’re weighing risk and benefit, right? And you have to do that based on that individual.
Dr. Richter: One hundred percent.
Jenny: Let’s talk a little bit about drugs like immunotherapy that are currently in clinical trials because this situation is having a huge impact on clinical trial participation and joining new clinical trials or even releasing new clinical trials. Do you want to share your perspective?
Dr. Richter: Absolutely. I just got off of a phone call about 20 minutes ago or just before this about clinical trials. It’s complicated right now. For those who don’t know, clinical trials are things that we do when a drug is not yet approved, and we need to run them through testing to make sure that they’re safe and the right doses for patients.
This affects people at a lot of levels. One is people who are already on clinical trials. People who are already on clinical trials, if the drug is working, we want to continue it. Every trial has a list of requirements that the FDA and the trial puts you through.
The FDA has actually released some guidelines to let us know that do what’s appropriate, meaning if you’re on a clinical trial and you’re responding well and it tells you that you need to come every week for blood work but your blood work has been great for months, we can back off. We don’t need to do it every week. The FDA is going to let us know that that’s okay in the long run. We’re trying to make adjustments, but if you’re responding well to a clinical trial, we’re trying to keep you on it.
For people who are going to go on clinical trials, the landscape of trials in myeloma has changed across the last decade. A decade ago, most of the trials were for people with no other options. Nowadays, many of the trials that we put patients on, there are other options. If there is a standard of care option that is at least it’s good, we’re going that direction.
We’re really trying to limit people going on to clinical trials right now, kind of across the board. Again, the handful of patients who really need it, because there’s absolutely nothing else available we are evaluating on a case-by-case basis but the reality is for many people, and obviously not all but for many people going to trials, there are other options.
I think the big thing this is impacting is a lot of people are very interested in going onto CAR T studies and bifunctional antibodies. Again, the same principle applies where if we have another option to put you on in the meantime, we will because the type of immunosuppression you get with a CAR T, may put you in unnecessary risk or infection for this time.
Jenny: How long does that typically last with CAR T?
Dr. Richter: The immunosuppression?
Dr. Richter: There’s two types of immunosuppression that we get with CAR T’s. One is cellular, and the other is humoral. Cellular is where your white blood count is low. For some people, that can last months. The other is humoral, those immunoglobulins or antibodies that you make. That can be low for even longer.
For some people, they have a good amount of immunosuppression that can last for three to six months and again, it’s not that that is an insurmountable feat, but right now, if we were going to put someone on a CAR T at their first relapse instead of giving them something like daratumumab and Revlimid or Revlimid and Ninlaro or something like that, we may opt for a standard of care at the moment.
Jenny: Interesting. Is the situation the same for the BiTEs and the antibody-drug conjugates in your opinion?
Dr. Richter: Absolutely. It’s the same thing because the main risk of CAR T’s is the cytokine release syndrome where when we put the CAR T into the patient, it activates the immune system and releases all these chemicals we call cytokines and you can have high fevers, low blood pressure, confusion, it can be very serious. The BiTEs have the same risk. Many of the trials right now with bifunctionals or BiTEs require multiple admissions to the hospital to monitor for CRS. We don’t want people being admitted three times in three weeks in the hospital right now. Those trials are shut down.
The antibody-drug conjugates are very interesting because we’re on the cusp of it some point in the next six months having belantamab mafodotin, this big BCMA antibody-drug conjugate approved. I think at the moment, we’re anxiously awaiting that drug to come out as another tool in our toolbelt. It’s going to hold up those trials as well for the moment, mostly from the requirements that trials need to keep you on study.
Jenny: Okay. Well, that’s really shifting a lot of things for a lot of different people. The development that’s happening in myeloma is so stunning that I just don’t want that to slow down because we do need these new therapies. Well, there’s a lot to think about.
Dr. Richter: Absolutely. No, it’s something that’s absolutely critical. I mean one of the things that we’re hoping is the next few drugs that are going to be approved, belantamab and bb2121, a lot of this is just waiting for the final information to reach significance and be filed with the FDA and although the FDA is going to be spending much time working on COVID-related therapies at the moment, we’re hoping that this doesn’t slow up those approvals, and that we can get them out to our patients that need it as soon as possible.
Jenny: Right, because they’re pretty close to being approved, it sounds like.
Dr. Richter: Absolutely.
Jenny: Let’s talk about issues that patients should consider. Who is specifically at the highest risk for developing this virus in terms of myeloma patients?
Dr. Richter: Absolutely. It’s something that we have to extrapolate from the data we have. The data that we have, and doctors are joining from all over the world to share pieces they have is literally changing moment to moment, hour to hour. Some of the biggest data we have comes from the Hubei province in Wuhan, China where they published this paper on March 9th in Lancet, which is this big journal talking about who really gets sick?
It seems that the people who really get the sickest are people over the age of 80 or people who are over the age of 60 who have significant comorbidities, the biggest one being lung issues. For people who are older or over the age of 80, those are the people who are at higher risk who really should practice social distancing as much as possible.
I always tell them for essentially all these people, they’ve spent their lives helping people, helping their families, helping their friends, this is a time to let us help them. Have your neighbor, have your kids send food to you, so you can social distance or for people who are over the age of 60 as significant comorbidities especially lung.
People have underlying COPD or asthma, those are the people we really worry about. If have underlying lung disease, the same thing applies. You have raised friends and family throughout the years, it’s time to lean on them to help you. I think those are the big watch words we’re trying to convince everyone of.
Jenny: Okay, great. What about other normal comorbidities that come with myeloma like kidney issues or are you seeing any greater incidence or concerns for people like that?
Dr. Richter: The one thing that is very much in question is being debated quite a bit is when the COVID virus started, one of the big questions that everyone was asking is how is it that older people seem to be getting sick but younger people don’t? Again, it’s not that younger people don’t get sick, they can still get it, they can still pass it along, but the very severe illness seems to be limited in younger people.
One of the theories, again, this is early on and the data may change tomorrow is that it relates to an enzyme called ACE, angiotensin-converting enzyme. This is a chemical that’s in our body that relates to our kidneys, and blood pressure. In fact, many people out there may be on ACE inhibitors. If you’re on a drug that ends with the word, “pril,” enalapril, quinapril, those are ACE inhibitors.
It seems that some of the people get sicker, this mechanism may be overactivated but the question we all asked is do we all stop our ACE inhibitors? The American College of Cardiology said no, there’s no evidence to stop them.
The recommendation is not to stop ACE inhibitors. In terms of other drugs to take or avoid, there’s a bit of conflicting data about NSAIDS, drugs like Advil or Ibuprofen or Aleve or naproxen. Originally, the WHO released the statement that patients should avoid Advil or NSAIDS and take Tylenol instead. They just released some statement today saying that maybe in question, they don’t know that for certain.
In general, patients with myeloma should avoid NSAIDs if at all possible anyway, so definitely Tylenol is preferred.
Jenny: Because of the kidney impact, right?
Dr. Richter: Exactly. What it turns out is what we think is the COVID is a Goldilocks phenomenon, meaning you want just the right amount of immune system. Too little, in the case of if you give things like NSAIDs, NSAIDs actually affect the immune system because they’re anti-inflammatory and inflammatory cells are what our immune system is. If you take too many NSAIDs, the concern is the virus can take root.
On the flipside, an overactive immune system may not be ideal as well. In fact, one of the drugs that we’re using in advanced COVID cases is a drug we use in people who get CAR T therapy. The cytokine release syndrome that people are at risk from with CAR T therapy, if they get it, it’s basically when their system gets too much of a chemical called Interleukin 6. That really drives these high fevers and low blood pressures. We have a drug called tocilizumab that block that. People get overactive cytokine release in CAR T therapy, we can shut it off with tocilizumab.
It turns out the same chemical that’s elevated in CAR T’s in people who have COVID, elevation of that compound is correlated with the worse outcome, and there was a paper release from China recently that 20 patients who are severely ill, essentially all of them had massive improvement when given tocilizumab.
Now, it’s not ready to give to everyone. It’s not clear that everyone needs it, but it’s another tool in our armamentarium for people who get very sick.
Jenny: I’ve read the paper on that. That was so interesting that that’s being tested because they have that myeloma connection with cytokine release, so interesting. I think the world is searching for solutions right now. It’s fantastic.
Should myeloma patients be proactively tested at their myeloma visits if they’re there already, if they think there might be some kind of symptoms? What do you suggest in terms of what symptoms should patients watch for and things like that?
Dr. Richter: Absolutely, and this is great, and the reality is I’ll give you the answer today of what I say but it’s going to change for the next few days because of the guidelines for testing are literally changing moment to moment. Depending upon where you live, the availability may be very different. So obviously, if you have any of the classic signs of COVID which are fever, shortness of breath, dry cough, you should be evaluated and tested.
My recommendation would be is to call your local physician’s office or urgent care center and see if there’s a way to be tested outside of an emergency room. It’s optimal to avoid emergency rooms if at all possible if you’re not very sick. Obviously, if you’re having significant trouble breathing, lethargic, really sick, then you have to go to the ER. But if you generally feel well and you take your temperature and it’s a little bit up, you have a little bit of a cough, try to do this outside of a hospital or clinic setting, see if you can do it in urgent care or in some of the drive by centers that are being set up.
If you’re already at your physician’s office and they’re able to test you, there is no downside to testing, there’s plenty of upside. Much of this comes out of data that was looked at in the province in Italy. They tested everybody. It turns out that even asymptomatic people have it. The benefit of knowing is that if you know you have it, you’ll avoid other people from getting sick. But again, the ability to test is going to be different from place and moment to moment.
Obviously, if you have symptoms that get tested, if you’re at a regular visit, you can ask and if they have the availability to, there’s no downside to being tested.
Jenny: It sounded like from some of that data that was coming out of Italy that you can have it for up to five days or something like that without having any symptoms. That’s part of the issue is that when you don’t know, you’re out and about and causing issues when you don’t even know it.
Dr. Richter: That’s part of the reason we’re seeing this steep rise is because it can be up to five days. For some people, it’s even longer until they have any symptoms. I think social distancing is really reaching appropriate levels now but unfortunately, the last couple of weeks, it’s taken a little bit of time for everyone to get on board with this so people may have been infecting others so as soon as there’s more testing available, we should all be tested as soon as possible.
Actually, someone had chimed in a Facebook post about this. Mt. Sinai actually just published a paper of the infectious disease in microbiology group at Mt. Sinai developed the first anti-body test for this. The testing that’s currently being done is to what’s called a PCR, polymerase chain reaction. Basically, it looks for little bits of the virus and that’s it. It tells you, you have a little bit of the virus, none of the virus, but this test that was just developed at Sinai is going to be rolled out probably for the next week, is looking for antibodies and there’s a lot of advantages of doing this.
The antibodies can be detected even after only a few days of symptoms. It’s a very efficacious test. It also lets us know who’s immune. If we know who’s immune, we can help work on developing vaccines and preventative strategies from that. The other issue with healthcare workers, we know that someone has had it, and is immune, we can send them back to work to help others. This is a major step forward and we’re very happy about it.
Jenny: Well, we need this test right away.
Dr. Richter: It was just developed yesterday. They published the paper. We’re going to roll it out as soon as this weekend. I mean that’s one of the things, you know, some of the testing that’s been done in clinical trials with a drug called remdesivir which was used to treat Ebola in Nebraska. Most of the time, trials like this take a decade to open up. This has been done in a matter of days and weeks through a horrible thing. It’s amazing to see the medical community. When I say the medical community, I’m not just talking about the scientists, nurses and doctors.
The people coming to clean the floor, the people who serve the food, everyone is taking a risk of all joining together along with the FDA to get therapies out as quickly as possible.
Jenny: It’s amazing and stunning. It’s just wonderful that this is happening. What is the waiting period? My son got tested yesterday and is like a five-day waiting period before he knows (turns out it is a 12 day waiting period :/). He’s kind of just hunkering down before he knows if he has it or not.
Dr. Richter: Yes. We’re speeding up all the tests. This I think has a less than 24-hour turnaround, but don’t quote me on that because this was developed within the last week. Getting up to commercial grade is a little bit -- that is all being rushed. It will be opened within the next week or so potentially even by this weekend, there’s still a short turnaround but I think across the board, every -- even the viral test where we’re getting shorter and shorter turnarounds.
Jenny: You talked about some symptoms that are serious enough to go to the hospitals, so shortness of breath, or being overtired, seriously overtired. Are there other symptoms patients need to watch for? Does it happen quickly? Do you need to act quickly? How much time do you have in doing it? Then you talked about going to the ER but if you test positive and let’s say you don’t have serious symptoms, they don’t need to go to the hospital necessarily, who should treat you? Should you go to the local clinics? Should you call your myeloma doctor and go there? What should patients do?
Dr. Richter: I think that one of the things we’re all aware of is that there’s a lot of unknown. The first thing I would say is when in doubt, call. If you have a temperature of 99.9 and you’re not sure, call. If you’re feeling relatively well, call. It doesn’t matter if it’s 2:00 in the morning, we don’t want people being stoic because what may be fine to wait at one point may be more urgent later on.
Close contact, and you can call anyone. You can call your myeloma doc, your primary care doctor, and we may end up working together. Someone called the other day who lives quite a bit away and said, where can I go get tested? I said, your local doctor will know the answer. He knows all the hospitals right around there. I don’t know all the hospitals in the small town in Tennessee.
I think in general, the symptoms have not been coming on as thunderclap like you’re fine one minute, not fine the next. Unfortunately, most people experience the flu, so I think it’s somewhat similar where you start feeling a little bit unwell and all of a sudden, over time, symptoms get worse and worse and I think at the end of the day, you know your own bodies.
If you know that’s something is really wrong, you call. If something is really, really wrong that you can’t catch your breath, or your fever is 105, that’s not necessarily a time you can wait for a call back, you may need to go to the ER. But all else being equal, it’s just a little bit of a cough, a little bit of a fever, and you otherwise feel well, call your local urgent care, call your myeloma doctor, your primary care, and we can all work together to find the best setting to be tested to avoid hospitalization if at all possible.
Jenny: Great. What are the typical treatments for COVID-19 for a myeloma patient and is it that any different from the normal population?
Dr. Richter: We’ve developed some algorithms here. We’re trying to work them out because the data’s changing day-by-day. That IVIG drug which is unclear if it helps or hurts, if your immunoglobulins are very low, we may give you some IVIG. What is arising is a drug called hydroxychloroquine, more commonly known as Plaquenil, that appears to have some really good effects in people who have COVID-19.
If you’re coming to the hospital and you’re short of breath and you’re requiring oxygen, we may up the ante and give you Plaquenil which can modulate the immune system. The steps beyond that become a little more complicated and it’s case-by-case.
One of the things we’re able to do here is measure those levels of IL-6 and if you’re starting to have more trouble breathing, and your IL-6 levels are high and clinically appropriate, we can give tocilizumab and we’re even about to open a clinical trial but have access potentially to compassionate use if needed. There’s a drug called remdesivir. Remdesivir was a drug that was designed to treat the Ebola virus previously. It’s available on limited access. (update: Gilead is pausing the emergency/compassionate use) For patients who are unfortunately very sick in the ICU, that’s an option.
Then the other options are kind of up in the air and case-by-case. Some of the older HIV drugs, ritonavir and lopinavir may have some anti-COVID activity that’s being looked at case-by-case. Chloroquine which is similar to hydroxychloroquine may also play a role. Unclear about steroids, whether or not they help or don’t. Again, if you’re having trouble breathing because there’s so much inflammation in the lung, we may give steroids and fortunately, myeloma patients know steroids better than almost anyone in the planet, but those are the main medicines we’re using right now.
Jenny: Okay, great. If somebody’s seeing a local doctor and they can’t access their myeloma specialist for some reason, what do the other doctors need to do about a patient’s myeloma when they’re being treated for COVID-19?
Dr. Richter: That’s an extremely important question. I think that I’m glad you asked because it oftentimes falls by the wayside. What we’re doing again is case-by-case. For the majority of people who developed COVID-19, we are stopping their therapy. Now, that may not be correct for everyone.
What I would highly recommend is people don’t take it upon themselves to stop, but to reach out to their oncologist or myeloma specialist and discuss with them what the risk and benefit? But for many patients, we’re holding the therapy to allow their immune system to kind of take care and a part of managing the virus as much as possible.
Jenny: Have you had a lot of patients test positive in your medical clinical?
Dr. Richter: We have not had many. We have had a few that we’ve had to manage with this and that has been our general strategy.
Jenny: So these would be just such crazy times. What can patients do to stay healthy or fit if they’re using normal social distancing, but I think people need to make sure that they’re not socially isolating also like both physically and mentally? Do you have any recommendations about that?
Dr. Richter: Absolutely. The three general principles of life, eat well, sleep well, and get exercise apply whether you have COVID-19 or not, myeloma or not, those are three very important things from a physical standpoint, so eating well. As many of us are socially isolated, this is not a time to just eat chips on the couch. Healthy eating is really important as much as possible obviously within reason.
If it’s difficult to get some of the fresher things, canned vegetables are oftentimes a better thing than having a box of donuts. Healthy eating is important. Sleep is very important. Everything is made better by good sleep and worse by no sleep. You should sleep as best you can. If you need something to help you sleep, reach out to your care team and we’re happy to prescribe something to help people to get to sleep because our minds start to race when we lie down at night after watching a whole day’s worth of craziness on the TV, and exercise.
Exercise is just a generally good thing physically immune-wise, et cetera. There are many ways that even though we often don’t exercise at home, so what my wife and son have been doing along with our daughter is doing home yoga. There are many stations on YouTube or on the television to show you how to do home yoga and home exercise. There are even some funny ones on YouTube which I wouldn’t suggest where people put oil down on kitchen floors and use it like a treadmill. I wouldn’t suggest that because you can slip and hurt yourself, but there are many low and no impact ways to keep things healthy.
The other thing you brought up which is something we’re hyper aware of and maybe not the optimizing is mental health. Mentally, this takes an enormous toll on a group of people who are already facing a mental toll that I can’t begin to imagine. You’re doing what you can to keep your mental status up and your mental health up, it’s crucial.
If you need medicine to help, it’s there. One of the things I highly suggest, it’s 2020. Facetime. Call people. Facetime with people. If there’s someone you haven’t talked to for a while, call them. This is the time to make sure that we stay interconnected by our phones. Now’s the time to use that to its maximum yield. You normally would call your kids once a week, call them once a day. Everyone’s at home, everyone has time on their hands right now except for the people on the front lines.
Take the time to call your loved ones, call your friends, engage with people. There are many ways technology can help us.
Jenny: That’s amazing. Great advice. Perfect advice. Well, I’d like to transition to some caller questions, so we have time for that. If you have a question for Dr. Richter, please call 347-637-2631 and then press 1 on your keypad, and I’ll be able to see if you have questions.
Caller: Hi, Jenny. It’s Jack. Great questions.
Dr. Richter: Hey, Jack. How are you?
Caller: I’m doing fine, and great answers from Dr. Richter. Since I can no longer ask him the question about the eating chips on the couch, I’m going to ask a little bit more about clinical trials. I know that bela and bb2121 are close to approval. Are those trials that the FDA would be looking at? I hope they’re already fully accrued.
Dr. Richter: It’s complicated because both of those drugs or both of those treatments have multiple trials. All of the bela trials are called DREAMM. There’s DREAMM 1, 2, 3, 4, 5, 6 and all of the bb21 are called KarMMA, KarMMA 1, 2, 3. The main studies are accrued, and we’re just looking for follow-up. I can’t answer the question of is the infection going to stymy the one little piece of data that they need?
My guess is that it will not. At this phase, where those drugs are where they’re literally due to be approved within this year, hopefully within the next couple of months, that it’s simply a question of the final follow-up from patients, the data, and all the paperwork that needs submission to the FDA.
I know that all the companies are working very closely with the FDA to minimize and impact COVID will have about getting these drugs up and running. That being said, the one thing that I would think about is let’s say they were both approved tomorrow, bela is a drug that gets manufactured, shipped and given in any office that can give infusions. BB2121 is a little more complicated. It requires leukophoresis. It requires manufacturing of the cells.
Even in normal conditions, it may have taken a little bit of time to get that up and running. But in speaking with the people at BMS Celgene, they’re still highly dedicated to getting this in the hands of patients as soon as it’s appropriate.
Caller: If a patient were in the middle of a clinical trial, I gather that if they were diagnosed with COVID-19 that you would end up stopping treatment associated with that trial?
Dr. Richter: That’s a really great question. The answer is not necessarily. It depends upon what the drug is, how bad the infection is, and the rules of the trial. What most trials have in the protocols is guidelines to say if something bad happens, you can hold the drug but oftentimes, it’ll say if the drug has to be held beyond let’s say four weeks, you can’t go back on the drug unless the sponsor says okay.
Under normal circumstances, let’s say you’re on a clinical trial, you get pneumonia and you’re off for four weeks, the study may say listen, you’ve been off for four weeks, we have to stop it. I think in this setting with everything up in the air, the FDA has been really gracious about letting us know that we need to do what’s in the patient’s best interest more so now than ever.
So, case-by-case basis but I think that if the infection is mild and people get over it, there’s a good chance that we can him back on study. I wouldn’t just stop study drug, but again, this is really case-by-case.
Caller: Thanks so much for your answers. I look forward the next time we see each other.
Dr. Richter: Absolutely, sir.
Jenny: Okay, great. We have many, many questions. We’ll ask everybody to limit their questions to just one. Go ahead with your question.
Caller: Yeah. Hi. I previously was a patient of Dr. Richter’s. There’s a lot of contradictory or amorphous information about how the disease can be COVID-19, how it can be contracted. One of the studies said that -- one of the doctors said that the disease lingers in the air, the virus lingers in the air. Can you get COVID-19 from breathing it in in an environment where you’ve been exposed to the virus in the air?
Dr. Richter: I think you’re asking the really important question. I would be lying if I could tell you exactly what we know because I think you put it perfectly that the information is somewhat conflicting. It is very amorphous. One of the things that we do know about COVID infection is that apparently, the viral load matters.
What that means is there’s some diseases where the amount of virus in you doesn’t really seem to mean too much, you either have it or you don’t, pregnant or not. But in COVID, the amount you have seems to matter. If you are literally sitting right next to -- if you’re living with somebody and you’re literally around them all day long and get continual viral particles into you, that is probably far worse than even if there’s a small amount that you inhale that has been out there.
Again, the data is changing daily. I think that in general, when people go out especially when you go out to markets, grocery stores, wearing masks is a great idea, the surgical masks are just fine. You don’t necessarily need an N95 mask, but I think you point out perfectly. We don’t have clear data and guidelines right now. As this moves on, we may learn more. What I’m doing to protect myself and my patients is you go out, you wear a mask but in general we know that people who get higher viral inoculum from being in close quarters with people who seem to have worse outcome.
Caller: Okay, thank you.
Jenny: Okay. Great question. Thank you so much. Go ahead with your question.
Caller: Hi, Jenny. This is Cindy. Hi, Dr. Richter.
Jenny: Hey, Cindy.
Dr. Richter: Oh, hi.
Caller: I was supposed to be there today talking to you in person. I think it’s so much more valuable, of course they wouldn’t have let me in the building anyway. My question is I’m reading a lot of different clinical trials are testing the effectiveness of different drugs just like you had said earlier in this show. Now, are those drugs only being given through a clinical trial, or are they being given whether or not you’re in a trial? Would you recommend if a myeloma patient does get COVID-19 to try to make it to the research centers instead of their community hospital?
Dr. Richter: All great questions. Many of these drugs are not very ubiquitous. If a drug has no real FDA approval, it’s really kind of hard to give. Remdesivir is not readily available. We can’t just give it to people. Tocilizumab is more available. We can make clinical decisions at the bedside and if we think the benefits out way the risks, we can give it but again, it’s a more severe step.
Hydroxychloroquine, Plaquenil, there are probably many people listening out there that are family members that are already on this drug, so that drug’s a lot more readily available and I think we’re more willing to give that in a place where we just don’t know the answers. When drugs are sitting in shelves that we have ready to go, more of an inkling to give them, some of them do need clinical trials but what’s really great is some of the drug companies are opening up outside of trials, Compassionate Use Program, so much in the same way that we have Compassionate Use Programs for myeloma.
For example, right now, belantamab is available through a Compassionate Use and Expanded Access Programs even outside of the clinical trial. Same thing is being done with some of these drugs.
What was your last question again?
Caller: Right. Should I try to make it to a research center or go to my community hospital?
Dr. Richter: It’s a complicated question. I think depending upon your symptoms, obviously if someone is very, very sick, you need to go to your closest center because time to getting those supportive care meds, the oxygen, the CAT scan, the IV fluid, those are critical and those can be given anywhere.
I think that if you are otherwise feeling well, or then this is a conversation you have with your care team -- because it’s a great question. If you live ten miles from your normal ER, but 15 miles from your myeloma center, it’s an easy decision. If it’s ten miles and 50 miles and you’re not feeling well, you shouldn’t go down there. The majority of what we’re doing can be administered at any center, so the default answer is closest but if you’re feeling well, it’s a great question to ask your care team.
Caller: Okay. Thank you very much. Hopefully, I’ll get to see you soon.
Dr. Richter: Looking forward to it.
Caller: All right. Bye-bye.
Jenny: Okay, great. Thanks, Cindy for your question. Okay. Go ahead with your question.
Caller: Hi, Dr. Richter. You spoke about IVIG as a potential measure to prevent infection although I think you said for some patients, it’s recommended, others it's not. What about Neulasta? Would that work for antiviral, or it’s only antibacterial?
Dr. Richter: Neulasta, it’s a really great question. When we talk about the immune system and there’s many, many parts of it and I wish Han Cho (Mt. Sinai mm doc) was here because he knows more about the immune system than any person on the planet. In broad terms, there’s the humoral and there’s the cellular. Humoral is the antibody that IVIG helps with. Neulasta helps with the cellular immunity and increases your white blood cell count. It tends to help increase your neutrophils which tend to do more to fight off bacterial infections. However, with antivirus, you are in the risk of a super superimposed bacterial infection.
It’s not uncommon that people get something like the flu or rhinovirus virus and the doctors still put you on antibiotics because you get a superimposed bacterial infection. We are using Neulasta, and people who present with low neutrophil counts, with low white blood cell counts to make sure they don’t get anything else. But in it of itself, it probably doesn’t do too much against COVID.
Caller: But for somebody who’s on maintenance therapy and is perpetually immunosuppressed, do you think it’s wise to get it preemptively, Neulasta, I mean?
Dr. Richter: It’s a great question. I mean the bigger question is if someone’s on maintenance and otherwise on remission and is always and is always neutropenic, the question is should maintenance be held right now? Again, this is a question to ask your myeloma care team, for many people like this that need the maintenance. We know we can’t stop it. We do give Neulasta, but for people who have been in remission for years and otherwise fine and always come in with their ANC at 900, this may be the time to hold off for a little bit.
Caller: Thank you.
Jenny: Okay. Great question.
Caller: Hi, Jenny. Hi, Dr. Richter. It’s Dana Holmes. How are you guys today? Thanks so much, Dr. Richter for spending the time with us.
Dr. Richter: Hey, how are you?
Caller: It’s just terrific. Really, it’s just your knowledge, it’s just so incredible. Thank you for that. I was super excited to read that paper yesterday about your colleagues at Icahn with that serum antibody titer assay because honestly, just my observation, that this past influenza season may have actually masked a lot of this COVID-19 including in myeloma patients so it would be really great for us to be able to tease out if any of us actually had it. I’m looking forward to seeing that hit the ordering supply chains.
Dr. Richter: Yeah, absolutely. This really -- as opposed to just telling us the virus is there or not, it lets us know who’s immune, it also means that workers don’t necessarily have to be fiddling with the virus itself, so it’s more safety for the people who are in the techs on the frontlines of this.
Dr. Richter: Again, if we know who’s immune, because part of the thing that COVID really makes it difficult is right now, if you have an upper respiratory tract infection, we don’t know. We don’t want to start breaking out some of these big guns like tocilizumab or atlizumab that have potential downsides if we know you already have antibodies and if there’s another infection.
More ways that we can help avoid unnecessary risk to people, always a big plus.
Caller: Absolutely. I can honestly see this helping somewhere down the road of when IVIG is actually pulled IgG so if perhaps, some of these antibodies are going to find it into the IVIG supply someday for everybody too. That’s really terrific. There’s another study that came out from France. It’s a non-randomized trial that coupled azithromycin with hydrochloroquine.
Dr. Richter: Hydroxychloroquine, yes.
Caller: Thank you. It was really impressive. I mean again, I wasn’t sure if it was mild or moderate cases or severe cases but most of those people who had the combo changed the PCR from positive to negative in just five days. I mean that’s like taking tamiflu for crying out loud.
Dr. Richter: The issue is because you can have this prodrome of no symptoms to begin with, those people may have converted to PCR negativity but that was the natural course. However, hydroxychloroquine may definitely improve this and azithromycin, that Z-Pak that we always get have these inflammatory properties.
Even though it’s not fighting off a bacteria, the anti-inflammatory properties of azithromycin which may help in terms of symptoms as well. I think your point is a really great one. We don’t know did that hurry up to get people negative viremic or there’s a negative viremic anyway, but it made them clinically better to get better. Either way, it's a win.
Caller: You were hearing the term immunocompromised, having a suppressed immune system and if one has it, that there’s obviously a higher risk for major complications from COVID. Cancer patients are obviously included in this and so are myeloma patients. We get that. We know that the risk of complications is higher and likely contracting it is higher, but what does it actually mean to be immunocompromised? Which biomark or metrics tell us our current immune status? Which labs do we look at?
I mean I would imagine our labs could can change daily so do we rely upon this to know our immune status at any given time? Is it prudent to do that or do we just air on the side of caution right now due to the very nature of having myeloma or smoldering myeloma in my case, knowing our immune function likely stinks and proceed just using the utmost caution?
Dr. Richter: If you continue to ask such great and relevant questions like this, we’re going to bar you from asking any further questions.
Caller: I am. No, I’m done.
Jenny: We have eight other questions.
Dr. Richter: This is a great note. It’s absolutely fantastic. The short answer is -- your last statement is perfect. Everyone should exercise extreme caution. At the end of the day, the immune system is not one lab test, it’s not even two lab tests. The majority of our immune cells and our immune functions, we don’t check on a regular basis, we don’t check NK cells, we don’t check our dendritic cells, our Tregs, we don’t check all of the individual components. The best we have is what our immunoglobulins are what is our white blood count and lymphocyte count.
One of the things that seems to have a negative impact on outcomes for COVID is lymphopenia, not neutropenia but lymphopenia, and the question is when people have lymphopenia get sick with COVID, was it because the virus itself made them lymphopenia or did they have lymphopenia from other reasons like myeloma or their drugs and we don’t know that answer.
I think looking out to maximize an individual’s lymphocyte count, their neutrophil count and their immunoglobulins right now is probably to an advantage, but someone I was talking to yesterday, introduced me to a term that I’ve never heard before that I’m going to steal from her, she says well, there’s not just immunocompromised and immunocompetent, there’s immunochallenge. She considered herself immunochallenged not immunosuppressed.
There’s shades of grey in there and because we don’t know every factor of it every time, I think right now, everything should be on the side of precaution.
Caller: Good. Thank you so much. Thank you so much for taking all my questions.
Jenny: Awesome questions. Okay, caller go ahead with you question.
Caller: Hi, Dr. Richter. My question pertains to I really started regimen of venetoclax, Velcade and dex, and specifically in order to minimize my visits to the office, I was wondering if I were to suggest to my myeloma specialist to pair Ninlaro instead of the Velcade with the venetoclax, would that be a safe pairing to suggest that in discussion in order to less frequently doctor’s office.?
Dr. Richter: I think it’s an absolutely phenomenal question to have. The realities we have very little data on that combination. The BELLINI trial which is the big registration trial, we actually know very well the risks and benefits of Velcade with venetoclax. We know a little bit less about Ninlaro and venetoclax. That being said, I think it’s a great idea to have that conversation.
There was a little bit of side effect overlap but I think the dosing can be done in such a way to make that safe. Again, there’s facets of your disease that he or she may know far better than I, but I think it’s an extremely reasonable thing to reach out to them and say listen, I want to minimize my visits, is there any way we can switch it over to Ninlaro and talk about it? I think it’s a great idea.
Caller: Great. I will do that. Thank you so much.
Dr. Richter: Of course.
Jenny: Great question. Okay, caller, go ahead with your question.
Caller: Yes. Hello, Dr. Richter. Thank you, Jenny. My husband is on Revlimid, and my question is there are components of this drug made in China and it will affect his ability to continue getting the Revlimid?
Dr. Richter: Really great question. It’s something a lot of people are asking. I can tell you that -- no, first of all the one thing about China is that in the last 24, 48 hours, there’s been no new cases last time I looked at the data from China, from Hubei province in Wuhan where this originated.
The fact that they’re on a down slope is actually a good sign globally about the light at the end of the tunnel of all this. That aside, I can tell you that the people at BMS, Celgene in particular who manufacture Revlimid have literally been on the phone nonstop and we’ve been in contact with them, making sure that people have continued supply of drugs.
I would not be concerned about that at the moment. I think that there are a lot of ways that we’re able to get over this. In a pinch, and I mean in a real pinch, there’s alternate dosing strategies where Revlimid can even be taken every other day instead of every day but I doubt we’re going to have to come to that because the companies have been really good about insuring that drugs are going to be available.
Caller: Thank you so much, Dr. Richter.
Jenny: Okay, great. Great question. Go ahead with your question.
Caller: Yes. Thank you, Dr. Richter and thank you, Jenny, for doing this. It’s a very good thing. This is Dennis. I’m a veterinarian actually. My wife has multiple myeloma, and she has it very significantly. But we’re waiting for a CAR T trial at this time. She has her cells harvested and so we’re about four or five weeks now from probably getting those cells.
Do you think we could one, go ahead with that? That’s the number one thing. Two, I’ve heard a lot and been reading a lot about just simple things like elderberry and how it may also be helpful in the immune system related. Then the third, hyperbaric oxygen has been used during the Spanish flu in 1918 and it was used successfully. This was hyperbaric air only with air pressure.
I know those are successfully treated for patients that had the Spanish flu and were near death, cyanotic, unconscious, taking their last breaths, and when they got in the chamber, they were able to then survive, actually to really survive after several treatments. Can you comment on those three things then for me, please? Thank you.
Dr. Richter: A whole lot there. CAR T is difficult. This is something, you know, obviously if she’s in line with a CAR T and her cells collected, she’s at one of the top myeloma centers so I can assure you whatever the decision that they decide on, I have no doubt it’s the correct one.
A lot of this depends upon the status of their hospital. If it’s a hospital that is being overrun by COVID, that changes the dynamic. How well controlled is your wife’s disease and what options they have. Let’s say we have all the freedom in the world and this is an earlier phase relapse and the bridging therapy she’s on is working perfectly, it may be the better part to delay the infusion and keep her on the bridging therapy until such time it becomes safer.
If this is a more advanced scenario where there are no really good options and they can still give it, I don’t think there’s a contraindication to go in ahead. However, if an alternative can be found that may be optimal as far as --
Caller: She’s not in any current bridging therapy at all right now. The doctors thought that we would be able to move right along from where she was to getting into the therapy. So getting her cells. She’s not in any bridging therapy at this time at all several weeks out.
Dr. Richter: No, but that means that they’re confident that even without therapy in that time, things will hold steady. Again, unfortunately, this is a study-by-study question and if you’re getting a CAR T without -- you don’t have to tell me where she’s going, I’m sure the doctors there have a well clear plan for this.
Caller: Thank you very much.
Dr. Richter: For elderberry and hyperbaric oxygen, I’ve seen those floating around. We just don’t know. Elderberry probably has some immune-modulating effects, unclear how much it helps. This maybe along the same lines as turmeric curcumin that a lot of people with myeloma take where it may have some positive effects but we don’t know fully how much, so that’s going to be a tough one, and hyperbaric oxygen is less available now because there’s just fewer indications for it, and unclear if the same mechanism by which it held off the flu will help.
The one thing I would say is as a veterinarian, I would ask you, one of the things I’ve seen floating around is a discussion that there are a number of ventilators that are available for large animals like pigs and elephants and giraffes that may be repurposed to use for people. I don’t know if you can comment on that.
Caller: Well, sure I could. I’m with basically an association called American College of Veterinary Emergency and Critical Care. In that college, we’re all basically diplomats in that college, we have donated, if you will, lent, if you will, our ventilators to many, many different institutions all across the country.
These are just good ventilators that are just having all the different ways of ventilating mostly small animal patients, big cats and dogs that are critically ill. That actually gets me into a question, we’re still hoping in our centers and we’re not ventilating our patients because those patients -- those who have ventilators went to the human hospitals, you guys know way better than we do.
But what about the transfer of COVID-19 on pets’ hair? To me, it’s like almost like a cardboard box. If it’s able to place viral particles on the pets’ hair, don’t you think that our veterinarians that are clinically caring for these patients should also be almost protected like you would an ICU doc as well with the N95 mask?
Dr. Richter: N95s are really only indicated this time for aerosolizing procedure. If you’re doing any procedure on an animal that’s aerosolizing, potentially aerosolizing, then an N95 mask with goggles is absolutely needed, for routine care, face shield surgical mask and gloves with gowns should absolutely suffice.
Caller: All right. Okay. Well, it’s good to have a chance to talk with you. Thank you so much.
Jenny: Thank you so much for your great questions.
Caller: Hi. Thank you, Jenny and Dr. Richter. I am possibly coming close to a relapse. The numbers were rising, and I had a spot on my zygomatic arch. My doctor increased -- went back to my old frequency on Pomalyst and – I can’t think of the name. I was so surprised you did that.
Dr. Richter: Dexamethasone?
Dr. Richter: Oh, Kyprolis.
Caller: Kyprolis, and we’re going to go that route until further notice, but I went and saw the radiation oncologist and they’re recommending me having radiation to that area on my left side, the corner of my eye and that arch area there.
That’s supposed to start next month. Then of course I’ll stop infusion. But what is this radiation going to do to my system and with the virus? Will it inhibit it, cause me to be more susceptible to it?
Dr. Richter: In general, not. Oh, sorry.
Caller: I know, but I have to go in every day for two weeks but it’s in a separate building. This is way off -- talking about protein inhibitors, someone has talked about them doing some studies on it and the COVID virus. I know there’s tons of like you said, medications out there. We don’t know yet. But I’m just throwing that out there. Anything about protein inhibitors and the COVID virus?
Dr. Richter: Do you mean proteasome inhibitors?
Dr. Richter: Oh, like carfilzomib? We just don’t know enough yet about that. In terms of --
Caller: I mean in a weird way, is it going to protect me?
Dr. Richter: Unclear. Again, there are immune-modulating drugs, drugs like Pomalyst and Kyprolis, it’s not that they kill every immune cell, they activate others so there may be some protective nature. It’s really case-by-case and unfortunately, we just don’t have enough information yet to say one way or the other.
The radiation itself to the zygomatic arch, depending upon the size is usually minimally toxic because it’s not a very large area. Your concern about going back and forth twice a day -- once a day, is a real concern. If you just started on KPD and the radiation is planned for a little bit of time but your symptoms are getting better because it’s shrinking, you may be able to hold off.
On the other hand, radiation and Kyprolis is generally a safe thing. It’s the radiation and pomalidomide that’s actually more of a concern because the two together can give you more lower blood counts.
Caller: Well, it would be discontinued. There’s no doubt about that. They’ve already told me that.
Dr. Richter: The other question that you may ask your radiation oncologist is, is there a way to do this in a fewer number of fractions? Depending upon the area of radiation and the need, sometimes, you need ten fractions so ten visits. Sometimes, you can do it in five. Sometimes, you can do it in one. I would reach out to your radiation oncologist because they -- understanding that you planned this, I don’t know if they told you five or ten sessions?
Caller: I think it’s ten. I’m not too sure because she said two weeks so I’m assuming ten because I had it in my head before. It’s going to half as much as what I had before. I think she said 24 use, if that makes sense?
Dr. Richter: It’s usually grey. If they do ten sessions, they often do 30 centigrade times ten to get 30 or he may be giving 240 a day times ten to give you a total of 24, but depending upon the type of radiation oncology, sometimes, they can do a higher dose in fewer fractions depending upon where the area is. You should ask them if they could do it in fewer fractions.
Caller: Well, they have to be careful about my eye and they told me about that. That spot was there a year ago from my PET scan and my numbers were going up just a little bit. I mean I’m still on the safe zone, but we are seeing changes. All they did was just increase the frequency a little bit back to what it used to be. They were trying to step back because of my white cell count. Right now, it’s holding okay.
Dr. Richter: Excellent. Well, I wish you the best.
Caller: Thank you very much.
Jenny: All right. Thank you so much for your question. We have one last question, then we need to go.
Caller: Oh, I’m sorry. I had a stem cell transplant, University of Maryland. After that, about three months after that, I had PCP pneumonia. I had bronchitis on and off. The doctors said to me, you know, I think it would be a good idea to get the IVIG. I’ve been doing that for the past five months and it has brought up my IVIG numbers -- my IgA and IgM are just very low, but it did boost that and I haven’t had bronchitis. I’ve been doing really well.
My question is do I discontinue going for the IVIG because of the jeopardy it would put me in with possibly going to the hospital to get the infusion? The infusion could last five hours. Do I -- I don’t know which way to go.
Dr. Richter: If you’re at the University of Maryland, you’re probably seeing Ashraf Badros or Mehmet Kocoglu?
Caller: No. Actually, Dr. Rapoport and he has sent me to GBMC, Greater Baltimore Medical Center, and my doctor there is Dr. Elman.
Dr. Richter: Oh, great group there. They’re a phenomenal group. What I can tell you is that these are -- unfortunately, the answer -- it’s a personal decision. I can tell you that if you’ve been not having infections and your IgG is essentially normal, risk benefit, I think that it’s not unreasonable to hold it but understand that you had PCP pneumonia which is still something we don’t see that often.
You may be someone who needs it more than others so really, I think your question is a great one. This is something that really should be directed to the team in Maryland and they’ll be able to just have ta discussion specifically for you, what are the risk benefits?
Caller: If all of the progress I have made with the IVIG, if were to miss one or two of the infusions, do I lose all the progress I’ve made?
Dr. Richter: No. In general, you don’t. But I would emphasize not just making the decision on your own because there are other little things that may be relatively insignificant to you but the team at Maryland will expertly say well, you know, because of this level or because of that clinical feature, you should really continue or they may say, your IgG is normal, you can hold it. You’re working with a great team, I know they will guide you the right way.
Caller: Okay. Thank you so very much. I really appreciate that.
Jenny: Thank you so much. Thanks for your question.
Thanks, everybody for all your amazing questions. Dr. Richter, thank you so much. This has been just an outstanding show. Unbelievable show with so much information. We will post the show later. It speaks to the need to see a myeloma specialist if you haven’t by now.
I just want to comment on a few other things that we have in terms of support. In terms of staying fit like what you were saying, Dr. Richter earlier about staying fit and keeping moving, we have a Muscles for Myeloma program that we’re running and it’s all virtual and you can join that and you can log your merits and chat with other people who are doing the same thing and coming up with creative ways to exercise.
We have a myeloma coach program that you can reach out to and find a myeloma coach to answer some of the simple questions to maybe offload some of those questions from your doctor, then we have the HealthTree platform. Since everyone’s at home, they can fill out their HealthTree profile because we will probably be running a COVID-19 study inside of HealthTree. So you can get all your information in there now.
But Dr. Richter, thank you so much for your time and sharing your expertise. It’s unbelievable.
Dr. Richter: My pleasure. Thank you so much for everything you do. We really appreciate it.
Jenny: Really, really unbelievable, your expertise and your willingness to share. Thank you so much, everyone, for listening to Myeloma Crowd Radio and get in tuned next time to learn more about the latest in myeloma research and what it means for you.