Tag Archive for: minimal residual disease

Is It Too Late for a Myeloma Second Opinion?

Is It Too Late for a Myeloma Second Opinion? from Patient Empowerment Network on Vimeo.

When is the best time to seek a second opinion? Dr. Joshua Richter discusses the benefit of seeking a consult with a myeloma specialist to optimize your care.

Dr. Joshua Richter is director of Multiple Myeloma at the Blavatnik Family – Chelsea Medical Center at Mount Sinai. He also serves as Assistant Professor of Medicine in The Tisch Cancer Institute, Division of Hematology and Medical Oncology. Learn more about Dr. Richter, here.

See More from Thrive Myeloma


Related Programs:

How to Thrive and Set Myeloma Treatment Goals

How to Thrive and Set Myeloma Treatment Goals

Defining the Myeloma Patient Role in Their Care

Defining the Myeloma Patient Role in Their Care

What Are Relapsed and Refractory Myeloma?

What Are Relapsed and Refractory Myeloma?


Transcript:

Katherine:

Randall writes, “I was diagnosed last year with myeloma, and my first treatment worked, but now I’ve relapsed. Is it too late to consider a second opinion or a consult with a specialist? Would that change anything?   

Dr. Richter:

It’s a phenomenal question. There have actually been studies to show that if you engage with a myeloma center at least once within your myeloma journey, you do better than someone who has never done that. So, it is never a bad time to seek out a specialist. And one of the good things that came out of COVID is telemedicine. So, if there’s not someone right in your area, reaching out to some of our advocacy groups to help connect you to physicians like me or any of my colleagues, we’re more than happy to see anyone, I’ll see you with an MGUS that’ll never bother you, as will all of my colleagues and people who work in myeloma.   

If you’ve had one prior line, 15 prior lines, anywhere in between. So, I think it’s always a good idea to see a specialist because he or she is more than happy to work with your local doctor to optimize your treatment without having to necessarily go to another center.

How Long Will Myeloma Maintenance Therapy Last?

How Long Will Myeloma Maintenance Therapy Last? from Patient Empowerment Network on Vimeo.

Dr. Joshua Richter, a myeloma specialist, reviews the goals of maintenance therapy and discusses the timeline for this type of treatment.

Dr. Joshua Richter is director of Multiple Myeloma at the Blavatnik Family – Chelsea Medical Center at Mount Sinai. He also serves as Assistant Professor of Medicine in The Tisch Cancer Institute, Division of Hematology and Medical Oncology. Learn more about Dr. Richter, here.

See More from Thrive Myeloma


Related Programs:

Is It Too Late for a Myeloma Second Opinion?

Is It Too Late for a Myeloma Second Opinion?

Key Factors That Guide Myeloma Treatment Decisions

Key Factors That Guide Myeloma Treatment Decisions

What Myeloma Patients Should Know About Treatment Monitoring

What Myeloma Patients Should Know About Treatment Monitoring


Transcript:

Katherine:

Isaac sent us this question. How long does the average myeloma patient remain on Revlimid? And is there a suggested time period? 

Dr. Richter:

Really great question. It depends upon the setting we’re looking at, and for the most part, a lot of people are probably asking about the maintenance setting. So, after initial therapy or after transplant, we put you on Revlimid. How long do we keep you on? The American adage has always been, “More is better,” so as long as you tolerate it and as long as it works. Outside of the U.S., they’ve done a couple of studies looking at one year and then stopping, or two years and then stopping.  

And in a big trial that got presented a year or so ago, they compared the two years then stopping versus just staying on, and the people who just stay on do better.  

So, now the current thinking is just keep you on long-term. What’s going to change that in the long term is we’re starting to use a technology called MRD, minimal residual disease, so, doing a marrow and trying to find one in a million or one in 10 million cancer cells.   

And then, there’s something called sustained MRD meaning if you do two MRD analyses at least 12 months apart and they’re both negative, we call that sustained MRD-negative.   

And, there’s a hint that some people on maintenance Revlimid who have sustained their MRD negativity, they may do just as well stopping versus staying on it. We don’t know exactly who that is yet, but that’s going to be better understood in the next few years.  

What Myeloma Patients Should Know About Treatment Monitoring

What Myeloma Patients Should Know About Treatment Monitoring from Patient Empowerment Network on Vimeo.

How do you know if your myeloma treatment is working? Dr. Joshua Richter, a myeloma specialist, reviews how treatment response is measured in myeloma and why it’s important to share any symptoms or side effects with the healthcare team.

Dr. Joshua Richter is director of Multiple Myeloma at the Blavatnik Family – Chelsea Medical Center at Mount Sinai. He also serves as Assistant Professor of Medicine in The Tisch Cancer Institute, Division of Hematology and Medical Oncology. Learn more about Dr. Richter, here.

See More from Thrive Myeloma


Related Programs:

Is It Too Late for a Myeloma Second Opinion?

Is It Too Late for a Myeloma Second Opinion?

What Are Common Myeloma Treatment Side Effects?

What Are Common Myeloma Treatment Side Effects?

How Long Will Myeloma Maintenance Therapy Last?

How Long Will Myeloma Maintenance Therapy Last?


Transcript:

Katherine:

So, once treatment has begun, how do you know if it’s working? 

Dr. Richter:

Absolutely. So, the majority of myeloma patients are what we call “secretory.” And by “secretory,” it means that the cancer cells secrete a protein that we can measure in the blood either an M-spike, which is an intact immunoglobulin like IgG and kappa, or a free light chain. It doesn’t make that IgG part, just a free kappa or free lambda. And basically, when these protein levels go up, we know the cancer cells are growing. When these go down, we know we’re killing the cancer cells. And we actually call your remission based on how much we lower it.  

If we lower it 25 to 49 percent, that’s an MR or minor response, or minor remission. 50 to 89 percent is a PR, partial response, partial remission. 90 to 99 percent is a VGPR, a very good partial remission, and then all gone in the blood and then we do a bone marrow is a CR or complete remission.  

For some people, their disease can be non-secretory where the cancer cells don’t make that protein anymore.  

And for those people, we need to do regular imaging to see if they have growths of myeloma we call plasmacytomas, or unfortunately, we need to do regular bone marrow biopsies to see how much of the bad cells are growing inside the marrow. 

Katherine:

All right. How do you know when it’s time to switch treatment? 

Dr. Richter:

So, in general, when patients fulfill the criteria for what we call “progressive disease” or PD, that’s the time to change, or intolerance that regardless of how we dose adjust, dose hold or add supportive care, it’s not tolerable for a patient to continue.  

Intolerance is a very personal thing. There are things that certain people are willing to tolerate and others not. So, we try to adjust that. Just like we have criteria for response, PR, VGPR, we have criteria for progression. And in general, it’s a 25 percent increase from your baseline and 0.5 increase in your M-spike or 100 increase in your light chains. So, when the disease numbers are going up, we tend to switch.  

Now, people may say, “But I feel fine,” and a lot of this is because you’re diagnosed with an amount of disease up here. We get you in remission, you’re down here. And once you go like this, we can see the writing on the wall and we’d rather be proactive than reactive. So, instead of waiting until the numbers get up here to cause trouble, once it goes from there to there, we intervene, change therapy to bring it back down. 

Katherine:

Dr. Richter, why is it essential for patients to share any issues they may be having with their healthcare team?  

Dr. Richter:

It is absolutely crucial because some things that may be very, very minor to them may be the tip of the iceberg of something very, very worrisome that we really need to investigate because sometimes, little problems are little now, and over time, they can become problems that we can’t so easily reverse. So, things like neuropathy, fatigue, or actually better yet, what I tell my patients is, “You know your body. If there is something out of the ordinary, big or small, let us know.”  

And I would way rather a patient tell me 10 things in a row that mean nothing than not tell me about that one thing that means something.  

So, for example, one of the disorders that’s associated with myeloma is called amyloidosis.  

And when amyloid attacks the kidneys, you start to have protein in the urine, and this looks like bubbles, like foam in the urine. So, if someone has no foam when they urinate, and then over a period of months to years, they’re starting to notice lots of foam, tell me because that means we may need to look for things like amyloid.  

So, really any time something changes.  

What Are Common Myeloma Treatment Side Effects?

What Are Common Myeloma Treatment Side Effects? from Patient Empowerment Network on Vimeo.

Myeloma specialist Dr. Joshua Richter reviews common side effects of myeloma treatment and strategies for managing them. 

Dr. Joshua Richter is director of Multiple Myeloma at the Blavatnik Family – Chelsea Medical Center at Mount Sinai. He also serves as Assistant Professor of Medicine in The Tisch Cancer Institute, Division of Hematology and Medical Oncology. Learn more about Dr. Richter, here.

See More from Thrive Myeloma


Related Programs:

How to Thrive and Set Myeloma Treatment Goals

How to Thrive and Set Myeloma Treatment Goals

How Can Myeloma Treatment Impact Kidney Health?

How Can Myeloma Treatment Impact Kidney Health?

How Long Will Myeloma Maintenance Therapy Last?

How Long Will Myeloma Maintenance Therapy Last?


Transcript:

Katherine:

Can you help us understand some of the common issues that myeloma patients experience and how they might be managed? 

Dr. Richter:

Sure. So, fatigue is an absolutely huge one. And fatigue can come from a lot of different things. One, fatigue can come from other medicines. A lot of patients have cardiac issues and may be on other medicines causing fatigue. So, optimizing your other clinical status is important. Anemia can lead to fatigue, so we monitor your blood counts very closely, and if they drop, can we provide medicines to boost them up? Drugs. Some of the therapies we have can cause fatigue, and one of the biggest ones is Revlimid.  

And I tell people what actually tends to help is you take the Revlimid at night instead of the morning because if you take it at night, it tends to maximize the fatigue while you’re already sleeping. If you take it in the morning, it tends to maximize at that horrible, coffee-needing hour of 3:00 p.m. to 4:00 p.m., or 4:00 p.m. to 5:00 p.m. where you’re like, “Oh, I’ve gotta lie down.” So, fatigue is a really big one. Neuropathy. Neuropathy is really getting less and less in our new patients because more of our modern drugs don’t cause it, but unfortunately, some patients still have neuropathy, and they may be using drugs like gabapentin or Lyrica.  

There’s some other really old drugs and new drugs that can help. Drugs like Pamelor, which is nortriptyline, or Cymbalta may help quite a bit, or another drug called Effexor. And many of these drugs may be used for anxiety and depression, but also work for neuropathy. And then, even going to things like the cannabinoids; things like marijuana derivatives may actually be able to help both in salves or even edibles may actually help some of the neuropathy issues. And then, we get into some kind of out there stuff like compounding ketamine to help with some of these salves or oral combinations. So again, a little bit of neuropathy, let us know because there may be some ways to help.  

Defining the Myeloma Patient Role in Their Care

Defining the Myeloma Patient Role in Their Care from Patient Empowerment Network on Vimeo.

Why should myeloma patients speak up and be active partners in their care? Dr. Joshua Richter, a myeloma expert at Mount Sinai, explains the importance of communicating with your healthcare team and the difference it can make in your overall care.

Dr. Joshua Richter is director of Multiple Myeloma at the Blavatnik Family – Chelsea Medical Center at Mount Sinai. He also serves as Assistant Professor of Medicine in The Tisch Cancer Institute, Division of Hematology and Medical Oncology. Learn more about Dr. Richter, here.

See More from Thrive Myeloma


Related Programs:

What Myeloma Patients Should Know About Treatment Monitoring

What Myeloma Patients Should Know About Treatment Monitoring

Key Factors That Guide Myeloma Treatment Decisions

Key Factors That Guide Myeloma Treatment Decisions

How Long Will Myeloma Maintenance Therapy Last?

How Long Will Myeloma Maintenance Therapy Last?


Transcript:

Katherine:

Well, tell me what you think the patient’s role is, then, in setting care goals.

Dr. Richter:

Absolutely. The patient has the most crucial role of course. And, one of the things is honesty and really being to a point of brutal honesty with how they’re doing. I always tell patients, “You don’t get extra points for suffering. It’s not that if you sit there in pain you’re going to do better. Let me know what type of pain you’re having.” And pain doesn’t just mean a bone is hurting, or a muscle’s hurting, we call somatic pain.

There can be neuropathic pain where the nerves hurt.

There can be emotional and spiritual pain. These things all need to be addressed. And if you are suffering in silence, we have a lot of tools nowadays not just medicines. We have people to talk to. We have resources. So, letting us in to help is one of the most crucial things because we’ve actually shown that if you actually improve some of these, you may actually improve overall outcomes. So, the patient, please, all we want to do on the care side of the equation is help.

Let us know what’s bothering you. It may be small to you, it may be big to us, or vice versa, but the more open you are, the better we can help.

Katherine:

What advice do you have for patients to help them feel confident in speaking up and becoming a partner in their care? 

Dr. Richter:

So, that’s not always easy for a lot of people to do, and for some people, no problem. They’ll speak up at the first sign of anything. One bit of advice I would give to people who may have concerns or may not feel as comfortable about doing this is first of all, there’s a lot of members of the care team. So, I have patients that may not want to mention it to me, but mention it to my nurse or the medical assistant, and we all talk. So, that’s one way.  

The other thing that I think may help is involvement in patient support groups, hearing what others have to say about similar experiences and learning from them, them learning from you, and that may actually give you more of a confidence to speak with your care team. But the advocacy groups like the MMRF and IMF have tons of local support groups where you can sit in, and specialists come and speak or people share stories. And I think that can be really helpful to figuring out your optimal journey.  

Myeloma Treatment & Research Updates From 2022 ASCO and EHA Meetings

Myeloma Treatment & Research Updates From 2022 ASCO and EHA Meetings from Patient Empowerment Network on Vimeo.

Myeloma specialist and researcher Dr. Krina Patel discusses highlights from the recent American Society of Clinical Oncology (ASCO) annual meeting and the European Hematology Association (EHA) 2022 Congress. Dr. Patel shares promising research updates related to approaches including: stem cell transplant, CAR T-cell therapy, and bispecifics.

Dr. Krina Patel is an Associate Professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center in Houston, Texas. Dr. Patel is involved in research and cares for patients with multiple myeloma. Learn more about Dr. Patel, here.

Related Resources:

How Does Immunotherapy Treat Myeloma?

What Is Myeloma CAR T-Cell Therapy?

Immunotherapy: Which Myeloma Patients Is It Right For?

Transcript:

Katherine:   

Dr. Patel, cancer researchers recently came together at the annual ASCO and EHA meetings. Are there any highlights from the meetings that myeloma patients should know about?

Dr. Patel:    

Yeah, so we had some amazing trials that were presented at both. And I got to actually go to Chicago for the ASCO meeting, and I’ll say we actually had a plenary session that was presented for myeloma. That doesn’t happen as often as we like. So, basically that was a study presented by Dana-Farber and all of the different groups around the U.S. that did a transplant study. And basically, they’re looking at patients who got induction therapy when they’re newly diagnosed with transplant versus they didn’t get transplant upfront. And it’s called the determination study, and it was to determine should everybody be getting a stem cell transplant.

Katherine:  

Right.

Dr. Patel:   

And this is a trial that’s been going on for over 10 years; that’s why it was so highly anticipated. And basically, the biggest thing that we saw was what we call progression-free survival; so, the time that the myeloma hibernates is what I call it, for PFS. Basically, patients who got transplant upfront, it was 21 months longer that it stayed hibernating than if you didn’t get transplant upfront. So, that’s the trial, that’s what it was looking at, and that’s all they could really say about it. The good news is, even patients who didn’t get transplant upfront but then got transplant in second remission tended to have a really good, long progression-free survival or hibernation in that second remission.

So, it still tells us that right now, a transplant is still important for the majority of our myeloma patients. And basically, that’s sort of what that trial showed.

Now, the difference is we do different types of upfront therapies and we have new things like CAR T and bispecifics that are coming up earlier. So, we’ll see in the future if it still holds up. But as of right now, it still holds up for transplant. The other big studies, of course, were some of our bispecific studies that use different antigens. So, antigens are the flags that are on the myeloma that we make these receptors for CAR T, so they can find the myeloma, or bispecifics go after that.

And basically, there are other antigens. BCMA, B-cell maturation antigen, is the big one that we use for everything right now. But now, we found even more antigens, which is fantastic.

So, we have something called FcHR5. We have something called GPRC5D. It’s like alphabet number soup, basically. But what’s really exciting is that these new antigens give us a different way of getting to that myeloma, especially if someone has already had a BCMA therapy and they’ve relapsed on that. Well, now we have even new ways to get to that myeloma cell. So, I think that’s some really, really exciting data.

And then, I’ll say the other big one was one of the CAR Ts, Cilta-Cel was something that they presented.

Again, this was two years after the last patient had gotten treated on the trial. And so far, they still have about 71 percent of patients that are still in remission two years after. So, that is huge.

Katherine:                  

Wow.

Dr. Patel:  

We’ve never seen that in relapsed refractory patients before, so we’re really, really excited to kind of have gotten that data to say, “Okay, we found a brand-new way of treating myeloma.” And it really is changing how we’re looking at even earlier lines of therapy now.

Katherine:   

Such promising news. That’s great.

What Is Myeloma CAR T-Cell Therapy?

What Is Myeloma CAR T-Cell Therapy? from Patient Empowerment Network on Vimeo.

How does CAR (chimeric antigen receptor) T-cell therapy work to fight myeloma? Dr. Krina Patel, a myeloma specialist and researcher, explains how this novel therapy uses your immune system to treat the disease.

Dr. Krina Patel is an Associate Professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center in Houston, Texas. Dr. Patel is involved in research and cares for patients with multiple myeloma. Learn more about Dr. Patel, here.

Related Resources:

How Does Immunotherapy Treat Myeloma?

Immunotherapy: Which Myeloma Patients Is It Right For?

Myeloma Treatment & Research Updates From 2022 ASCO and EHA Meetings

Transcript:

Katherine:   

What is CAR T-cell therapy?

Dr. Patel:    

So, CAR-T cells are sort of a biologic immune therapy where we are able to take T cells, a type of lymphocyte which help us, normally. All of us have them in our blood.

They come from our bone marrow, go into our blood, and they sort of go around in the blood and look for bad things, pathogens. So, infections, even cancer cells, our T cells help get rid of all of those bad things that we’re not supposed to have. And they each have a receptor. And so, T cells have this night vision, and they’re made for a specific type of pathogen out there that we aren’t supposed to have that can hurt us.

And so, what we can is to either take your own T cells out, or sometimes with something called allo CAR-T use a normal donor’s T cells. And when we take them, we basically can put a new receptor in there, a new night vision; and so, now they are trained to go after something that’s specific on the myeloma instead of a bacteria or a virus or anything. And basically, we grow those cells, and then we give those cells back to our patient after a low dose of chemotherapy, just so these T cells can go in, find the myeloma, use that night vision to find that myeloma wherever it is, kill, and then it actually causes other immune cells in your system to come there and start helping to kill as well.

And then, they start coming back down again. And so, really, it’s a novel way of using your own immune system, or somebody else’s, but to actually enhance both by the target to get that myeloma precisely as well as making more of them so that there’s enough to go around and kill all the cells that we possibly can.

Relapsed and Refractory Myeloma Defined

Relapsed and Refractory Myeloma Defined from Patient Empowerment Network on Vimeo.

Myeloma expert Dr. Krina Patel reviews the difference between relapsed and refractory myeloma and how these distinctions may impact care and treatment.

Dr. Krina Patel is an Associate Professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center in Houston, Texas. Dr. Patel is involved in research and cares for patients with multiple myeloma. Learn more about Dr. Patel, here.

Related Resources:

Expert Advice for Newly Diagnosed Myeloma Patients

The Role of a Myeloma Specialist on Your Care Team

Myeloma Induction and Consolidation Therapy Defined

Transcript:

Katherine:  

Dr. Patel, could you define what relapsed myeloma is?

Dr. Patel:     

Yes, so as of today, for the majority of our patients we can’t cure myeloma to the point where we treat it, and it’s gone forever, right? I’m hoping one day we get there. And we’re getting better, but we’re not there yet. However, myeloma’s very, very treatable. So, what relapsed means is that, once you’ve had initial therapy after you’ve been diagnosed, our goal is to get that myeloma to as low as possible level so that it hibernates as long as possible. But eventually, that myeloma’s going to start waking back up. So, when it does, that’s called a relapse. That now, the proteins are coming up, the myeloma cells are growing and we need to do something to knock it back down again. So, that’s relapsed disease.

Katherine:

How is that different from refractory myeloma?

Dr. Patel:

That’s a great question. We talk about relapsed refractory all the time for myeloma. So, refractory actually means that your myeloma started waking up while on a certain medication. So, if you were on no medicines and then your myeloma came up, that’s considered relapsed. That’s not refractory. However, biggest example I can give you is when patients are on maintenance therapy after stem cell transplant, for instance. When they’re all on maintenance and their myeloma starts coming up while on maintenance, then they are considered refractory to that drug; so, if it’s lenalidomide (Revlimid), if it’s bortezomib (Velcade), whichever one it is.

So, any time the myeloma’s coming up while on active treatment, you become refractory. So, we talk about triple refractory or penta-refractory, and what that really means is how many drugs is your myeloma refractory to.

So, if you’re refractory to a proteasome inhibitor plus an immunomodulatory drug plus a CD38 antibody, right – I can give you examples of all of those, but basically different categories –then you’re considered triple refractory. And the more refractory it is, the harder it is to treat and the more novel therapies we need.

Katherine:

So, if a patient is taking three or four different drugs, how can you pin it down to know which drug or all of them are causing the refractory myeloma?

Dr. Patel:

So, it would be all of them. Let’s say, salvage therapy. You’re on three different medications or four different medications, usually three. We would say, if the myeloma’s coming up while you’re on all of them, you’re technically refractory to now all those medications.

Katherine:

All of those. Okay, all right.

Thriving With Myeloma: What You Should Know About Care and Treatment

Thriving with Myeloma: What You Should Know About Care and Treatment from Patient Empowerment Network on Vimeo.

What does it mean to thrive with myeloma? Myeloma specialist and researcher, Dr. Joshua Richter discusses the goals of myeloma care, reviews treatment options –including research updates – and shares tools for taking an active role in decisions.

Dr. Joshua Richter is director of Multiple Myeloma at the Blavatnik Family – Chelsea Medical Center at Mount Sinai. He also serves as Assistant Professor of Medicine in The Tisch Cancer Institute, Division of Hematology and Medical Oncology. Learn more about Dr. Richter, here.

Download Guide

See More from Thrive Myeloma


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How Could Clinical Trials Fit Into Your Myeloma Treatment Plan?

How Could Clinical Trials Fit Into Your Myeloma Treatment Plan?

The Latest in Myeloma Research: Updates from ASH 2021

The Latest in Myeloma Research: Updates from ASH 2021

Updates in CAR T-Cell Therapy for Myeloma from ASH 2021

Updates in CAR T-Cell Therapy for Myeloma from ASH 2021


Transcript:

Katherine:

Hello, and welcome. I’m Katherine Banwell, your host for today’s program. Today’s webinar is about how to live and thrive with myeloma. We’re going to discuss myeloma treatment goals and how you can play an active role in your care. Before we meet our guest, let’s review a few important details. Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Let’s meet our guest today. Joining me is Dr. Joshua Richter. Dr. Richter, welcome. Would you please introduce yourself?

Dr. Richter:

Hi. Thank you for having me today. My name is Joshua Richter.

I’m an associate professor of medicine at the Tisch Cancer Institute Icahn School of Medicine at Mount Sinai and the director of myeloma at the Blavatnik Family Chelsea Medical Center of Mount Sinai.

Katherine:

Great. Thank you for taking the time to join us today. There were two major cancer meetings recently, ASCO and EHA. Are there research updates from those meetings that myeloma patients should know about?

Dr. Richter:

Absolutely. These are some of the biggest meetings that we have every year that attract all types of people, patients, caregivers, physicians, nurses, Pharma, even investors from all over the world. We’re coming off of the back-to-back American Society of Clinical Oncology and European Hematology Association meetings, and there were a couple of really important updates and data. One of them at ASCO actually had what we call a plenary session.

A plenary is the top type of session at any one of these congresses, and it was around something called the DETERMINATION trial which looked at something a lot of patients may be familiar with, the notion of getting VRd, Velcade, Revlimid, and dexamethasone, with or without getting a stem cell transplant as part of their initial treatment. Now, many years ago when our initial therapy was not so good, we showed that transplant was better than what was good 30 years ago.

But, we have better treatments now. So, do we still need high-dose chemotherapy and stem cell transplant?

And what was really interesting about this data set is that if you do get a transplant upfront, you do seem to have a longer PFS, progression-free survival, meaning you stay in remission longer if you get your transplant as part of your initial therapy. However, there was no difference in overall survival, meaning how long you actually lived. And this may not make a lot of sense at first, but think about patient one who stays in remission longer, but because now their disease is a little more refractory, the subsequent therapies don’t work as well as compared to the person who doesn’t get the transplant upfront.

And then those latter therapies work a little better, and when you add them all up, they come out about the same. So, I think one of the things that comes out of this is, “Do I need the transplant?” No, you don’t need the transplant as part of your initial therapy.

We’re still trying to figure out who really needs it and who doesn’t, but you can always never do it or save it for a later time. So, that was really one of the big things that came out of the ASCO meeting.

Katherine:

What about EHA?

Dr. Richter:

So, EHA had a lot of updates both in terms of CAR T-cell therapies and bispecific antibodies, and bispecific antibodies are near and dear to my heart. They’re my big passion in myeloma, and I had the honor of presenting updated data on the Regeneron 5458 bispecific antibody at EHA.

This is a BCMA CD3 bispecific. So, many people may be familiar with monoclonal antibodies like daratumumab, which is just an antibody that gets injected and attacks the cancer.

Bispecifics are molecules that are injected that have two arms. One grabs onto the cancer cell; the other grabs onto your own immune cells that we call T cells and activates them to attack the cancer. Very interesting new therapy.

Very exciting, and very high response rates in people who have had tons and tons of treatment. So, in people that have seen almost everything in the highest dosing group of the study, 75 percent of people responded, which is very, very high.

But more notably, the big side effect we look out for called CRS or cytokine release syndrome, that’s where we activate your T cells and they get so activated they can cause other problems. That can be pretty high in some of our immune therapies, but in this drug, there’s only 38 percent, and all of this was relatively minor. It wasn’t the really big stuff.

So, the reason why this is so near and dear to my heart is that some of these therapies like CAR T have to be given in a major center that does transplants.

But bispecific antibodies, if put together the right way, can be given in your local hematologist’s, oncologist’s office. So, a lot of great potential long-term get everybody treated with these drugs. And then, one or two other little things that I thought were really huge, one was the combining of bispecific antibodies. Studies called the TRIM protocols combined two different bispecific antibodies, one called teclistamab, and one called told talquetamab. Each got combined with daratumumab.

So, not only are we already seeing just the bispecific by itself, we’re starting to combine it and seeing unbelievable response rates. That was updated at EHA, which was groundbreaking. And then in CAR Ts, two things really caught my mind. One was the CARTITUDE-2 data basically giving CAR Ts earlier on to patients had a 100 percent response rate. Can’t really do better than 100 percent. So, it’s not just about getting 100 percent of people in remission.

It’s keeping them there and curing them, and it starts by getting 100 percent of people to respond. So, really looking forward to see how this develops.

But one of the other things was another CAR T that’s coming out of China that targets two different things. It targets BCMA and CD19, both of which can be found on myeloma cells, although CD19 is actually on the myeloma stem cell. It’s a little kooky. But one of the big issues with CAR Ts is manufacturing time. Right now, it takes four to eight weeks to make them. But in this construct, they were able to make them, it took them between 22 and 36 hours. So, for many people, they were able to manufacture the CAR Ts, theoretically, for patients within one day.

So, if we can not only get this therapy to work but shrink the manufacturing from a month or two to a day or two, that would make this more accessible to more patients, get them to their treatment on time. So, the sky’s the limit with our immune options right now.

Katherine:

Excellent. Since this webinar is part of Patient Empowerment Network’s Thrive series, I thought we could start by getting your opinion on what you think it means to thrive with myeloma.

Dr. Richter:

Absolutely. And I love that term. I recently chaired a 5K walk for the MMRF, and the word that is thrown around a lot in cancer is “survivorship.” And, I got up there and I said, “That’s not a word I like to use. I like to use the word “thrivorship.” So, I love that you’re using this word because to me, surviving is an important part of dealing with cancer, but it’s the first step. Thriving is the goal. The goal is not to just get through it. It’s to go beyond it. It’s to do everything you want to do in life: personal, family, business, anything you want.

If you want to spend your time fishing, if you want to spend your time skydiving, if you want to spend time with your grandkids, and enjoying that time, and as much as humanly possible, keeping the notion of cancer way out of your brain. To me, that is thriving and not just surviving with a diagnosis like myeloma.

Katherine:

That helps us guide through the conversation as we continue on. Getting the appropriate myeloma care is, of course, part of thriving. So, let’s talk about treatment. How would you define treatment goals?

Dr. Richter:

Sure. So, treatment goals are different for each different individual because unfortunately, myeloma tends to affect people who are older. So, whereas the goals for an 85 or 90-year-old diagnosed with the disease is maybe things like, “I don’t want to suffer. I don’t want to have as many side effects,” but the goal is not to live 40 years, that’s different from a 40-year-old who may say, “I’m willing to tolerate certain side effects because I want to live as far as possible.” So, in reality, there always has to be this huge balance. And as with anything in medicine, an open dialogue with your care team is crucial to understand what your goals are because a lot of us make assumptions on both sides.

The patient may assume that we want certain things out of this. We may assume the patient wants certain goals. Really open, vibrant discussions where there are no taboos, there’s nothing wrong to say. I’ve had patients say, “I don’t care what happens. My granddaughter is getting married next year. I need to be there.

Anything beyond that, I don’t care.” That’s their goal. They’re entitled to their goal. I will work with them within that construct. So, really being open about what the goals are. Right now, what I tell patients is, especially for younger patients who if you’re already 85 or 90, you’re getting closer and closer to how long you’re likely to survive even without myeloma.

It’s kind of hard to have a 90-year-old have a 30-year survival. We’re not living to 120 just yet anyway. But for most of my patients, I say my goal is to either keep you in remission so long that you pass from something else many years from now, or to keep you moving until we have a cure that we can just give you and then make sure that that cure, that you’re able to accept it. That your body’s intact, your bone marrow’s contact, and this is something we can provide for you.

Katherine:

Well, tell me what you think the patient’s role is, then, in setting care goals.

Dr. Richter:

Absolutely. The patient has the most crucial role of course. And, one of the things is honesty and really being to a point of brutal honesty with how they’re doing. I always tell patients, “You don’t get extra points for suffering. It’s not that if you sit there in pain you’re going to do better. Let me know what type of pain you’re having.” And pain doesn’t just mean a bone is hurting, or a muscle’s hurting, we call somatic pain.

There can be neuropathic pain where the nerves hurt.

There can be emotional and spiritual pain. These things all need to be addressed. And if you are suffering in silence, we have a lot of tools nowadays not just medicines. We have people to talk to. We have resources. So, letting us in to help is one of the most crucial things because we’ve actually shown that if you actually improve some of these, you may actually improve overall outcomes. So, the patient, please, all we want to do on the care side of the equation is help.

Let us know what’s bothering you. It may be small to you, it may be big to us, or vice versa, but the more open you are, the better we can help.

Katherine:

Yeah, that’s great advice. Before we move on to discussing how the treatment choice is determined, let’s define a couple of terms that are often mentioned in myeloma care. What does it mean to be refractory and how is that different from relapsing?

Dr. Richter:

Great question. So, these terms have very specific definitions in myeloma. “Relapsing” just means that the disease is coming back. So, you had myeloma that was measurable, you went into a remission, and now it is showing signs that it’s coming back. We call that “relapsing.” And depending upon what type of myeloma, we have specific definitions. So, if you’re IgG kappa and you make an M-spike, if your M-spike goes up at least 0.5 and at least 25 percent, we call that “relapsing.” If you’re a light chain, it’s gotta go up by at least 100. But, you’ve gotta make sure the units are right.

“Refractory” means that you either did not respond or you’re progressing on or within 60 days of your last treatment. So, I put you on Revlimid maintenance, and you’re on Revlimid, and your disease gets worse. You are now relapsed and refractory to Revlimid. If I give you a transplant and then I put you on nothing, and two years later your disease comes back, you’re relapsed but not refractory.

Katherine:

What I would like to look at is because everyone’s different, what’s going to work for one patient might not work for another. So, how do you choose which treatment is right for a patient?

Dr. Richter:

Really great question. So, unfortunately, myeloma, we don’t have the granularity just yet to say exactly what’s going to work for everyone. Our goal is to kind of be what I like to think of as urinary tract infections. You have a UTI, you pee on a dish, we put little discs of antibiotics and a couple of days later, we’re like, “You have an E. coli and Cipro will work.” You get the Cipro and it goes way. We don’t really have that outside of a few drugs. We do know that the drug venetoclax works really well in people who have a very specific type of translocation in their myeloma cells, something we call translocation (11;14).

But for the most part, we don’t know, and we have lots of options and we decide what drugs to use based on three factors: disease-related factors, treatment-related factors, patient-related factors. So, patient-related factors. Are you older or younger? Fit or frail? Do you have comorbidities? If you have a lot of neuropathy from diabetes, I don’t want to give you a drug that’s going to cause more neuropathy. If you have a lot of cardiac issues, I’m not going to give you a cardiac drug. Disease-related factors. Is your disease growing fast or slow? Can I give you some pills or do I need to give you intravenous immediately to stop it? Is it pressing on a nerve? Do I need to add radiation?

So, those are some of the big factors. And then, treatment related factors. Have you had certain other drugs? So, if you’re refractory to Revlimid, I may not want to give you Revlimid again. If you have a lot of side effects or didn’t respond well to Revlimid, I may not want to use another drug similar to Revlimid like Pomalyst.

I may want to choose another class. So, that’s kind of putting all of that together to come up with a treatment choice because there’s no clear guideline.

Katherine:

Right. Can you help us understand some of the common issues that myeloma patients experience and how they might be managed?

Dr. Richter:

Sure. So, fatigue is an absolutely huge one. And fatigue can come from a lot of different things. One, fatigue can come from other medicines. A lot of patients have cardiac issues and may be on other medicines causing fatigue. So, optimizing your other clinical status is important. Anemia can lead to fatigue, so we monitor your blood counts very closely, and if they drop, can we provide medicines to boost them up? Drugs. Some of the therapies we have can cause fatigue, and one of the biggest ones is Revlimid.

And, I tell people what actually tends to help is you take the Revlimid at night instead of the morning because if you take it at night, it tends to maximize the fatigue while you’re already sleeping. If you take it in the morning, it tends to maximize at that horrible, coffee-needing hour of 3:00 p.m. to 4:00 p.m., or 4:00 p.m. to 5:00 p.m. where you’re like, “Oh, I’ve gotta lie down.” So, fatigue is a really big one. Neuropathy. Neuropathy is really getting less and less in our new patients because more of our modern drugs don’t cause it, but unfortunately, some patients still have neuropathy and they may be using drugs like gabapentin or Lyrica.

There’s some other really old drugs and new drugs that can help. Drugs like Pamelor, which is nortriptyline, or Cymbalta may help quite a bit, or another drug called Effexor. And, many of these drugs may be used for

anxiety and depression, but also work for neuropathy. And then, even going to things like the cannabinoids; things like marijuana derivatives may actually be able to help both in salves or even edibles may actually help some of the neuropathy issues. And then, we get into some kind of out there stuff like compounding ketamine to help with some of these salves or oral combinations. So again, a little bit of neuropathy, let us know because there may be some ways to help.

Katherine:

Are kidneys impacted by any of the medications that patients take?

Dr. Richter:

So, kidneys are an excruciatingly important part of myeloma, and d in my mind, one of the keys to long-term survival and outcome. So, there are three things that I tell all of my patients to help preserve long-term kidney health. Two of them are easy to wrap the head around. One is a little bit harder. Number one, keep yourself well hydrated. The kidneys are like a filter. Think, like, the filter for your car. If you drove 100,000 miles in the desert and didn’t change your oil, there’d be problems. So, especially now that there’s warmer weather, by the time you already feel yourself dehydrated, you’re about 10 to 15 percent low on the total amount of body water you need.

So, especially if you’re going out there doing yard work, playing with the kids or grandkids, make sure you’re drinking plenty of water. Two, avoid NSAIDs. Drugs like Aleve, or naproxen, or Advil, or ibuprofen can be harmful to the kidneys. So again, please discuss with your care team. There may be better alternatives to treat your pain without hurting the kidneys. And the third is when all else possible, and avoid intravenous contrasts for CAT scans. Now, the IV contrast you get for MRIs is called gadolinium. It’s not harmful to the kidneys. But, the contrast for CAT scans is iodine-based, and although the newer formulations are better, it can still hurt the kidneys.

So, my advice is the following. If you’re in the ER at 2:00 a.m. in the morning and they want to do an urgent CAT scan with IV contrast, let them do it. It’s likely not going to be an issue. If you go to see an orthopedist and they say, “I want to get a better look at that leg that’s bothering you. I’m going to get a CAT scan with IV contrast,” tell them to call me. We’ll find an alternative.

Katherine:

Okay. All right. Good advice. Thank you. So, once treatment has begun, how do you know if it’s working?

Dr. Richter:

Absolutely. So, the majority of myeloma patients are what we call “secretory.” And by “secretory,” it means that the cancer cells secrete a protein that we can measure in the blood either an M-spike, which is an intact immunoglobulin like IgG and kappa, or a free light chain. It doesn’t make that IgG part, just a free kappa or free lambda. And basically, when these protein levels go up, we know the cancer cells are growing. When these go down, we know we’re killing the cancer cells. And we actually call your remission based on how much we lower it.

If we lower it 25 to 49 percent, that’s an MR or minor response, or minor remission. 50 to 89 percent is a PR, partial response, partial remission. 90 to 99 percent is a VGPR, a very good partial remission, and then all gone in the blood and then we do a bone marrow is a CR or complete remission.

For some people, their disease can be non-secretory where the cancer cells don’t make that protein anymore.

And for those people, we need to do regular imaging to see if they have growths of myeloma we call plasmacytomas, or unfortunately, we need to do regular bone marrow biopsies to see how much of the bad cells are growing inside the marrow.

Katherine:

All right. How do you know when it’s time to switch treatment?

Dr. Richter:

So, in general, when patients fulfill the criteria for what we call “progressive disease” or PD, that’s the time to change, or intolerance that regardless of how we dose adjust, dose hold or add supportive care, it’s not tolerable for a patient to continue.

Intolerance is a very personal thing. There are things that certain people are willing to tolerate and others not. So, we try to adjust that. Just like we have criteria for response, PR, VGPR, we have criteria for progression. And in general, it’s a 25 percent increase from your baseline and 0.5 increase in your M-spike or 100 increase in your light chains. So, when the disease numbers are going up, we tend to switch.

Now, people may say, “But I feel fine,” and a lot of this is because you’re diagnosed with an amount of disease up here. We get you in remission, you’re down here. And once you go like this, we can see the writing on the wall and we’d rather be proactive than reactive. So, instead of waiting until the numbers get up here to cause trouble, once it goes from there to there, we intervene, change therapy to bring it back down.

Katherine:

Dr. Richter, why is it essential for patients to share any issues they may be having with their healthcare team?

Dr. Richter:

It is absolutely crucial because some things that may be very, very minor to them may be the tip of the iceberg of something very, very worrisome that we really need to investigate because sometimes, little problems are little now, and over time, they can become problems that we can’t so easily reverse. So, things like neuropathy, fatigue, or actually better yet, what I tell my patients is, “You know your body. If there is something out of the ordinary, big or small, let us know.”

And I would way rather a patient tell me 10 things in a row that mean nothing than not tell me about that one thing that means something.

So, for example, one of the disorders that’s associated with myeloma is called amyloidosis.

And when amyloid attacks the kidneys, you start to have protein in the urine, and this looks like bubbles, like foam in the urine. So, if someone has no foam when they urinate, and then over a period of months to years, they’re starting to notice lots of foam, tell me because that means we may need to look for things like amyloid. So, really any time something changes.

Katherine:

Anything. Yeah. I want to make sure that we get to some of the audience questions. So, let’s start with this one. PEN community member Sal sent in this question prior to the program. “What is the difference between myeloma and multiple myeloma?”

Dr. Richter:

A really great question. For the most part, the terms are synonymous. We abbreviate multiple myeloma as myeloma. But along those lines, and I literally saw a patient today who said, “Why is it called multiple myeloma?” Well, when you have a group of bad plasma cells that forms a tumor, we call that a plasmacytoma, “cytoma” meaning “bad cells,” and “plasma” because they’re plasma cells. And when you have one of them, it is a solitary plasmacytoma. Once you have two of them, it’s multiple myeloma because it’s in multiple spots in the marrow or multiple spots in the body. So, for our purposes, we use them interchangeably, but that’s where the “multiple” comes from.

Katherine:

Okay. Isaac sent us this question. How long does the average myeloma patient remain on Revlimid? And, is there a suggested time period?

Dr. Richter:

Really great question. It depends upon the setting we’re looking at, and for the most part, a lot of people are probably asking about the maintenance setting. So, after initial therapy or after transplant, we put you on Revlimid. How long do we keep you on? The American adage has always been, “More is better,” so as long as you tolerate it and as long as it works. Outside of the U.S., they’ve done a couple of studies looking at one year and then stopping, or two years and then stopping.

And in a big trial that got presented a year or so ago, they compared the two years then stopping versus just staying on, and the people who just stay on do better.

So, now the current thinking is just keep you on long-term. What’s going to change that in the long term is we’re starting to use a technology called MRD, minimal residual disease, so, doing a marrow and trying to find one in a million or one in 10 million cancer cells.

And then, there’s something called sustained MRD meaning if you do two MRD analyses at least 12 months apart and they’re both negative, we call that sustained MRD negative.

And, there’s a hint that some people on maintenance Revlimid who have sustained their MRD negativity, they may do just as well stopping versus staying on it. We don’t know exactly who that is yet, but that’s going to be better understood in the next few years.

Katherine:

Okay. Randall writes, “I was diagnosed last year with myeloma, and my first treatment worked, but now I’ve relapsed. Is it too late to consider a second opinion or a consult with a specialist? Would that change anything?

Dr. Richter:

It’s a phenomenal question. There have actually been studies to show that if you engage with a myeloma center at least once within your myeloma journey, you do better than someone who has never done that. So, it is never a bad time to seek out a specialist. And one of the good things that came out of COVID is telemedicine. So, if there’s not someone right in your area, reaching out to some of our advocacy groups to help connect you to physicians like me or any of my colleagues, we’re more than happy to see anyone, I’ll see you with an MGUS that’ll never bother you, as will all of my colleagues and people who work in myeloma.

If you’ve had one prior line, 15 prior lines, anywhere in between. So, I think it’s always a good idea to see a specialist because he or she is more than happy to work with your local doctor to optimize your treatment without having to necessarily go to another center.

Katherine:

Yeah. Well, thank you for all of that, Dr. Richter. And, please continue to send in your questions to question@powerfulpatients.org and we’ll work to get them answered on future programs. So, Dr. Richter, we’ve talked a lot about why patients should play a role in their care.

What advice do you have for patients to help them feel confident in speaking up and becoming a partner in their care?

Dr. Richter: So, that’s not always easy for a lot of people to do, and for some people, no problem. They’ll speak up at the first sign of anything. One bit of advice I would give to people who may have concerns or may not feel as comfortable about doing this is first of all, there’s a lot of members of the care team. So, I have patients that may not want to mention it to me, but mention it to my nurse or the medical assistant, and we all talk. So, that’s one way.

The other thing that I think may help is involvement in patient support groups, hearing what others have to say about similar experiences and learning from them, them learning from you, and that may actually give you more of a confidence to speak with your care team. But, the advocacy groups like the MMRF and IMF have tons of local support groups where you can sit in, and specialists come and speak or people share stories. And I think that can be really helpful to figuring out your optimal journey.

Katherine:

And knowing that you’re not alone –

Dr. Richter:

Absolutely.

Katherine:

– in how you’re feeling. As we close out this conversation, I wanted to get your take on the future of myeloma. What makes you hopeful?

Dr. Richter:

So, we’ve had what we call Gestalt switches in myeloma. And what I mean by that is let’s rewind decades ago. We gave chemotherapy. Chemotherapy was designed to kill any cell that divides rapidly because that’s what cancer cells like to do.

It kills the good and the bad. It makes your hair fall out, throw up, horrible stuff. It doesn’t work too well. Then about 20 years ago, we started this switch to the novel therapies, Revlimid, thalidomide, Velcade, and then a decade later, daratumumab. And now, we’re having targeted agents which spend more time targeting the bad stuff, less time doing off-target stuff, really ramping things up.

We are at the precipice of a brand-new Gestalt switch in myeloma.

The immune world. The immune therapies. And right now, T-cell redirection therapy is what we call it either with CAR Ts, where we take your T cells out, engineer them, and put them back into your body all revved up, or we give you an off-the-shelf, bispecific that grabs onto your cancer and your T cell and, brace yourself, we even have trispecifics, which can engage your myeloma, another cell in your body, and yet another cell.

If you go on clinicaltrials.gov, which lists all the trials for everything, every disease, there are over 3,000 active trials in myeloma.

And what I tell people is when I first started and I sat across from a patient, I would say, “I’m really sorry. It’s not curable.” And now I say, “We are curing some people today by accident.” But over the next period of time, we’re going to do this deliberately and more frequently. And the goal is and always has been 100 percent of cure for 100 percent of patients, 100 percent of the time.

And, I kind of feel right now we’re almost like that 2001: A Space Odyssey when the obelisk lands. We have these immune therapies. We know they’re great. How do we combine them? How do we use them? How do we take all these great tools and turn it into a cure for everyone?”

And with so many great partners between advocacy groups and Pharma and patients and cancer centers, we’re going to collaborate and we’re going to start getting those answers in my lifetime, and I could not be more excited about that.

Katherine:

Oh, I bet. I bet. It seems like there’s been so much progress and hope in the field. Dr. Richter, thank you so much for joining us today. It’s been a pleasure.

Dr. Richter:

Thank you so much for having me. I’d love to come back anytime.

Katherine:

And thank you to all of our partners. To learn more about myeloma and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for joining us.

Updates in CAR T-Cell Therapy for Myeloma From ASH 2021

Updates in CAR T-Cell Therapy for Myeloma from ASH 2021 from Patient Empowerment Network on Vimeo.

Myeloma specialist, Dr. Omar Nadeem, shares the latest updates in CAR T-cell therapy from the 2021 American Society of Hematology (ASH) annual meeting. Dr. Nadeem discusses long-term study results and optimism for the future of CAR T-cell therapy.

Dr. Omar Nadeem is the Clinical Director of Myeloma Cellular Therapies Program and Director of Myeloma and Plasma Cell Pathways at the Dana-Farber Cancer Institute. Learn more about Dr. Nadeem, here.

See More from Thrive Myeloma


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The Latest in Myeloma Research: Updates from ASH 2021

The Latest in Myeloma Research: Updates from ASH 2021

How Could Clinical Trials Fit Into Your Myeloma Treatment Plan?

How Could Clinical Trials Fit Into Your Myeloma Treatment Plan?

An Expert’s Hopeful Outlook on Myeloma Research and Treatment

An Expert’s Hopeful Outlook on Myeloma Research and Treatment 


Transcript:

Dr. Nadeem:

My name is Omar Nadeem, and I’m at the Dana Farber Cancer Institute in Boston, Massachusetts. I’m an instructor of medicine at Harvard Medical School, and I direct the myeloma cellular therapies program at Dana Farber.

Katherine:

Dr. Nadeem, you’ve joined us from the American Society of Hematology Meeting in Atlanta. Can you share any highlights in myeloma from the meeting?

Dr. Nadeem:

Yeah, it’s a very exciting time in myeloma therapeutics. We’re seeing a lot of new agents that are being reported at this meeting, showing very promising results.

Then we’re also fine tuning the way we treat myeloma patients by looking at different combinations in all lines of therapy, whether it be front-line or relapsed setting, to try to really understand which treatments are the best and then also more importantly, which treatments do we need to continue patients on, etcetera as they’re going through their myeloma journey. So, lots of updates with important trials at this meeting so far.

Katherine:

We’re hearing a lot about the promise of CAR T-cell therapy. Is there any research news in CAR T-cell for myeloma treatment?

Dr. Nadeem:

Yeah. So, we’ll have a presentation later today, actually, updated results of the CARTITUDE-1 study, which is looking at cilta-cel, which is an anti-BCMA directed CAR-T cell product.

And this trial is a phase-1/2 study looking at some patients with relapse in refractory multiple myeloma that has been reported previously to have a very, very high response rate and very high rates of MRD negativity.

So at this meeting, with just longer follow-up, which is what we’re looking for in terms of how long these responses last, we’re starting to see that the median duration of response is now almost 22 months, which is very impressive looking at the data and comparing it to some of the other CAR-T products that are either under study or the one that’s currently approved.

So, that looks very promising. And also notably, we had some concerns initially about toxicity with this particular product. But that really hasn’t been seen with longer follow-up. So, we’re not seeing a toxicity signal, particularly as it relates to neurological toxicity, with the longer follow-up. So, that presentation will be later today. We look forward to seeing the updates, but so far this looks very encouraging and this is what we anticipate to be the next product that’s available in the market for myeloma.

How Is Myeloma Treatment Effectiveness Monitored?

How Is Myeloma Treatment Effectiveness Monitored? from Patient Empowerment Network on Vimeo.

Once you begin myeloma therapy, how do you know if it’s working? Dr. Saad Usmani, a myeloma expert, shares how patients are monitored via various tests and reviews how minimal residual disease (MRD) testing plays a role in myeloma care.

Dr. Saad Usmani is the Chief of Myeloma Service at Memorial Sloan Kettering Cancer Center in New York City. Learn more about Dr. Usmani, here.

See More From INSIST! Myeloma


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Which Tests Are Essential to Diagnose and Treat Myeloma?

Which Tests Are Essential to Diagnose and Treat Myeloma?

How Are Cytogenetics Used in Myeloma Care_

How Are Cytogenetics Used in Myeloma Care?

Questions to Ask Your Doctor About Essential Myeloma Testing

Questions to Ask Your Doctor About Essential Myeloma Testing


Transcript:

Katherine Banwell:

Once a patient begins therapy, how do you monitor whether a treatment is working?

Dr. Usmani:

So, as part of the diagnostic work-up, we typically have identified in the blood using serum protein electrophoresis and serum free light chains. What kind of myeloma proteins these – that particular patient’s myeloma cells are making. And we can monitor them every cycle of treatment. So, every three or four weeks.

And that’s the most noninvasive way of seeing if the treatment is working. The second obviously important thing is if someone has symptoms. If they have kidney damage, if they have bone pain, all of those things start improving as you’re getting treatment. And then in some patients, we’re also looking at imaging like PET CT scans at certain time points. And at some point, we do also look at the bone marrow biopsies to see what’s really going on in the factory.

Katherine Banwell:

We often hear the term MRD, or minimal residual disease used in the myeloma space. So, what is it exactly and how is it used in patient care?

Dr. Usmani:

So, minimal residual disease is a way to measure how much myeloma is left over in a given patient.

And historically, we were simply looking at the serum proteins and the light chain levels along with just the morphology of the bone marrow to see if – kind of determine a response. But we can have a much deeper assessment of how many cancer cells as a leftover from a bone marrow biopsy by different measurements. Someone can be in a complete response with M-Spike is gone. The light chains have normalized.

Yet they can still have 10,000 – 100,000 myeloma cells still in the bone marrow. And just using the bone marrow biopsy the way that we used to, we won’t be able to see them. We’ll just see, “Oh, these look like normal plasma cells.” So, using next-generation sequencing and flow cytometry, we can look at normal myeloma cells at a very deep level – one out of one million.

But these tests are highly specialized. And especially the flow cytometry requires a lot of expertise. The NGS requires good sampling at the time of diagnosis as well as subsequent specimen 

What Should You Ask Your Doctor About Myeloma Testing?

What Should You Ask Your Doctor About Myeloma Testing? from Patient Empowerment Network on Vimeo.

Testing and test results may affect your myeloma care and treatment. Dr. Nina Shah, a myeloma expert, shares key questions to ask your doctor about testing and reviews testing techniques for myeloma. 

Dr. Nina Shah is Associate Professor of Medicine in the Fepartment of Medicine at the University of California San Francisco (UCSF) and treats patients at the Hematology and Blood and Marrow Transplant Clinic at UCSF Helen Diller Family Comprehensive Cancer Center. Learn more about Dr. Shah, here.

See More From INSIST! Myeloma


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What Key Steps Should Follow a Myeloma Diagnosis

What Key Steps Should Follow a Myeloma Diagnosis?

How Does Myeloma Testing Affect Care and Treatment

How Does Myeloma Testing Affect Care and Treatment? 

What Standard Testing Follows a Myeloma Diagnosis_ (1)

What Standard Testing Follows a Myeloma Diagnosis?


Transcript:

Katherine Banwell:

If a patient wants testing beyond the standard, what should they be asking their doctors for?

Dr. Shah:

Well, thankfully a lot of these tests can be done as a standard. We actually have some approved testing for it. So, the most important thing is to ask the doctor at all. For example, the patient may ask, 1.) “When will my next bone marrow biopsy be?” and 2.) “When I get that bone marrow biopsy, will you be looking at cytogenetics and FISH?” and 3.) “When you get the bone marrow biopsy, will you be also looking for minimal residual disease?” And finally, “What technique will you use to look for that minimal residual disease?” There are different ones that the patients might find useful to know about.

Katherine Banwell:

What are some of the different techniques?

Dr. Shah:

There are a variety of ways that we can look for minimal residual disease. One of them is called flow cytometry. What that is is you send all the cells that are in the bone marrow through a chute, and in that chute you can sort of detect one or however many cells that are – that have a specific characteristic on their cell surface.

You think of it as a bunch of balls with lollipops sticking out of it. And based on the characteristics of those lollipops, you can tell if there are any plasma cells or myeloma cells. Another thing we do with minimal residual disease, another technique, is called the next-gen sequencing or NGS.

And for that, we need to know the specific DNA sequence that is very personal to your myeloma cells. So, your particular plasma cell or the cancer cell will have a sort of sequence, a specific sequence that can be identified when you’re first diagnosed. And if you have access to that tissue, that can be sent off to the company, and they use that as sort of a template or a measure – an individual identification. And then, they scan the subsequent bone marrow samples against that to see if there’s any sequence that matches that original one, and that’s the way you can detect one in a million positive cells, if there are any. 

How Is Minimal Residual Disease (MRD) Testing Used in Myeloma Care?

How Is Minimal Residual Disease (MRD) Testing Used in Myeloma Care? from Patient Empowerment Network on Vimeo.

Myeloma expert Dr. Nina Shah explains minimal residual disease (MRD) and how the results of this test may impact patient care and treatment.

Dr. Nina Shah is Associate Professor of Medicine in the Fepartment of Medicine at the University of California San Francisco (UCSF) and treats patients at the Hematology and Blood and Marrow Transplant Clinic at UCSF Helen Diller Family Comprehensive Cancer Center. Learn more about Dr. Shah, here.

See More From INSIST! Myeloma


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What Are the Goals of Myeloma Treatment? 


Transcript:

Katherine Banwell:

What is minimal residual disease testing, and when should it take place?

Dr. Shah:

Minimal residual disease is exactly what it sounds like. It’s the disease that you can’t see under the microscope, but it’s still there.

And I sort of equate it to the little deep food particles that are in a pot after you clean it and really, really scrub it, but still, something is in there. And that’s what it is for myeloma. And really, that depends on how sensitive your test is. We now know we can test for at least one in a million cells by some advanced techniques, and we like to test to see if there’s any disease left after certain treatments are done – for example, after a patient undergoes an autologous stem cell transplant.

Katherine Banwell:

What impact do results have on care decisions?

Dr. Shah:

Minimal residual disease testing can be useful for patients to understand the true burden of their disease. For example, it may be that there’s no more M-protein in the blood, or the light chains are normal, or even the bone marrow showed no plasma cells. But the minimal residual disease testing may show that, in fact, there are a few cells still in there, and that can help patients to decide, “Yes, I want proceed with maintenance therapy,” for example, or “No, I would not like to.” Although, we generally recommend it, patients like to have as much information as possible to make their decisions. 

Empowered AML Patient: Ask the AML Expert

Empowered AML Patient: Ask the AML Expert from Patient Empowerment Network on Vimeo.

For acute myeloid leukemia (AML) patients, how can they get the best care no matter location? Watch as expert Dr. Catherine Lai and AML patient Sasha Tanori discuss advancements in AML detection and treatments, the use of remote monitoring, questions to ask if you suspect you have AML, how AML can vary by age, and clinical trials access for optimal care.

See More from Best AML Care No Matter Where You Live

Related Resources:

What Treatments Are on the Horizon for Acute Myeloid Leukemia Patients?

What Treatments Are on the Horizon for Acute Myeloid Leukemia Patients?

What Role Does a Multidisciplinary Team Play in AML Care?

What Role Does a Multidisciplinary Team Play in AML Care? 

How an AML Survivor’s Resilience Saved Her Life 


Transcript:

Sasha Tanori:

I want to start off by saying, thank you so much for joining me, Dr. Lai, I greatly appreciate it.

Dr. Catherine Lai:

Thank you for having me.

Sasha Tanori:

Dr. Lai, early on before my diagnosis, AML, many of my doctors I saw dismissed my symptoms and attributed them to me being plus-sized. Can you share with us how detecting AML has evolved over the last several years?

Dr. Catherine Lai:

Yes, and I’m sorry to hear that, but what I would say about the diagnosis is that how we diagnose patients with AML, unfortunately, hasn’t changed significantly in the sense that we still have to rely on our standard techniques with the bone marrow biopsy. But what I would say is that the technology for how we risk-stratify patients and subsequently treat patients has improved because we have a better understanding of the molecular characteristics of AML now, and so it has helped us in terms of being able to identify more targeted treatments, where patients are more likely to respond and help us with both our short-term and our long-term plan.

Sasha Tanori:

Right, got it. My next question is, can you speak on how monitoring and treating AML has changed during the pandemic?

Dr. Catherine Lai:

Yeah, so unfortunately, as you experience it, you spent your induction in the hospital for several weeks, and when you’re able to be in the hospital with support, either from friends or from family, it makes the experience much, much easier and with COVID, especially at the height of the pandemic, we weren’t allowed our hospital. And I know several of my colleagues as well, the hospitals weren’t allowing any visitors and that put a lot of stress on the patient, on family members, on the staff, the nurses, the physicians, really the whole care team. Just because we were needing to spend extra time to make sure that everybody was updated, so either if we couldn’t do it on FaceTime, having to make sure other phone calls later, which is just…it is what it is. And we made the best of the situation. Currently, we are allowing to have a limited visitor policy, which is helpful. I think the other thing that has really changed is what we consider when we’re starting treatment, if patients obviously need induction chemotherapy and need to be in the hospital, we don’t change the recommendation based on that, but if there are patients who…

Dr. Catherine Lai:

There are options whether or not the patient is done inpatient versus outpatient, I think that that’s a huge consideration in terms of quality of life and how we manage those patients.

Sasha Tanori:

Can you speak to the advances and treatment options for high-risk AML patients?

Dr. Catherine Lai:

Yes, so fortunately, we have made a lot of progress in the AML space, that is one thing that is really exciting, I would say. Since 2017, there have been nine FDA approvals for AML, and prior to 2017, and we have been using the same chemotherapy for the last 40 years. Now, that’s not for lack of trying. There are many leukemia physicians who have been working at this for the duration of their careers, but AML just is very heterogeneous, and it’s very smart. It’s smarter than we are, and it’s constantly changing, and so that has made it challenging in terms of being able to treat it. So, there are newer treatment options, both modifications to traditional chemotherapy as well as other targeted therapies that have improved the landscape for AML and high-risk AML in particular. That’s awesome.

Sasha Tanori:

Dr. Lai, I think another factor that played a role in my diagnosis is somewhat being delayed is my age, I was 24 at the time, what are some questions others who suspect they have AML should ask to rule out the diagnosis?

Dr. Catherine Lai:

So, Sasha, that’s a really good question. And what I would say is that, as you are aware, the median age of AML diagnosis is 68, so not to say that we don’t have young patients…I have plenty of young patients, but it doesn’t come to…it’s not a common thing to think about in younger patients right off the bat, the other thing that contributes to that is also AML compared to other cancers is an uncommon cancer. There are only 25,000 cases of newly diagnosed in the United States per year because it’s not as common in younger patients and because it’s not that common…doctors often want to rule out other simple things rather than just going straight to a cancer diagnosis though, unfortunately, that can lead to some delays, what I would say in young patients who are healthy is that they shouldn’t have low blood counts that can’t be explained for other reasons. So, I think having prompt attention in terms of if their blood counts are abnormal, to really understanding why they’re abnormal, and those are things that can be easily work up, and if all those things are rolled out, then you’re talking about doing a bone marrow biopsy I don’t like to do procedures for unnecessary reasons, but it’s one of those things that you can also…

I mean, I think if you have a physician who is the astute and is thinking about that, that you can…you can get to a diagnosis pretty quickly, I mean AML is a diagnosis in the name acute. It comes on acutely, so that means days to week, so I suspect you are probably feeling very well and over a very short prior of time felt very unwell, and you’re very in tune to your body, and that is very important because patients are smarter than we give them credit for, and so being persistent and knowing that something is wrong goes a long way. Again, I’m sorry that you had to deal with that, and I’m glad that they finally made the right diagnosis, but I think just awareness and education. While it is an uncommon disease, I think having a larger burden and strain that happen on younger patients because you haven’t been working for the majority of your life, and it takes a huge toll on what your potential is, both as a person, but economically and all sorts of things. So it’s a huge problem

Sasha Tanori:

Does prognosis of AML vary by age?

Dr. Catherine Lai:

So, yes and no. So let me answer that in two steps, so it does in the sense that older patients are more likely to have more comorbidities, so more medical problems, and so therefore have a higher likelihood of having complications, and also as patients get older, they acquire more mutations and more abnormality, so those molecular abnormalities, and so therefore, older patients then are become more challenging to treat as well. What I would say though, is that we typically risk-stratify based on molecular factors, so the different mutation than somebody has and the age and the comorbidities don’t necessarily play into that role of stratification, so for example, whether or not you’re receiving a transplant or not…age is a factor, if you’re kind of in that little risk category, the intermediate risk category, the other thing I would say is that for young patients, they are able to tolerate because many don’t have medical problems, so they are able to tolerate treatment better, so when I’m talking about numbers and likelihood of response and overall survival, those…all those mediums assume that somebody is in their mid-60s, and so I adjust the numbers because for younger patients that those numbers are likely higher…

Because they’re less likely to have complications.

Sasha Tanori:

Right. I had many medical professionals that participated early on in my care. Can you speak on the role of the multidisciplinary care team that plays in AML care?

Dr. Catherine Lai:

Yeah, this is…this is an excellent question. I would say that treating leukemia is a team sport, everybody has their role, and it’s not just one person, and this is part of why I love treating leukemia patients, is that we’re able to engage multiple players, everybody is good at their particular thing, and so one analogy is that…we’re kind of like a baseball team, is that you want everybody to be able to do their own…have their own position. What a standard for our center is that we have the leukemia physician, there’s a specific leukemia nurse, we engage our social worker very early on, and also our cancer nutritionists and physical therapist and occupational therapist so we all work together at different parts of the treatment journey to make sure the patient is getting everything that they need and the whole person is being taken care of.

Sasha Tanori:

Right. AML patients, just like anyone else, want to live and live a very long time. Are AML patients at risk for secondary cancers, and are there any studies that speak on this?

Dr. Catherine Lai:

Yeah, so I would say everything has its risk and benefits at the time of diagnosis, you need the chemotherapy in order to get into remission, and then if you need the transplant, whether or not you’re getting radiation and then further some chemotherapy before the transplant, so that’s not without risks, so especially in a young patient, for example, in your particular case, you’re at risk for secondary treatment-related MDS and other bone marrow-related disorders that could occur, most patients who are in their 60s who, if they live long enough would be at risk, but most of those patients will die of something else before you have that opportunity. As a young patient, the other thing to be aware of, especially with, given that you’ve had transplant, is that the increased risk of cardiovascular effects, as well as making sure in patients who have had your whole-body radiation, other effects in terms of their thyroid, lung function, and then screening earlier for other cancers. So in terms of looking at studies, we know that these risks are slightly increased and that monitoring starts a lot sooner, especially in young patients. So I think just being aware of what you need to do.

Dr. Catherine Lai:

We also have a survivorship clinic, which I think is really important to help understand, you know what your risks are, because once your leukemia is in remission, we don’t want you to develop other medical problems, so it’s important just for patients to be educated so that they know how to take care of their body at each stage of their…again, of their journey.

Sasha Tanori:

Alrighty, after getting a bone marrow transplant three years later, I’m still dealing with graft-versus-host disease or GVHD, but there are other obstacles that I’m also facing. Does GVHD ever truly go away or is it something that I’m going to have to learn to live with?

Dr. Catherine Lai:

Yeah, I wish I had a magic answer for you. Our data is that it gives us guidance for each patient, but then also each patient as an individual and how they respond to different medications, and the nuances of that is…it can be different. So what I would say is that there are patients who you have chronic GVHD for years and it can eventually go away, and in some patients, they deal with it for a lifetime, you’re young enough, and I’m hopeful enough that at some point it will improve and get better. So I would be cautiously optimistic that things will improve.

Sasha Tanori:

I’m…I’m trying my best.

Dr. Catherine Lai:

It’s hard.

Sasha Tanori:

Yes, it’s very hard. Yeah, my care team suggested a clinical trial for a new drug focusing on improving my lung function, fortunately, my lungs improved on their own. Dr. Lai, not every AML patient is offered clinical trial as a care option, what advice you have for AML patients who are seeking clinical trial and what’s the best way to locate one?

Dr. Catherine Lai:

Yeah, so this is an area, a huge area of unmet need, I would say in general, across all oncology trials, and I think less than 10  percent of the patient population is on trials, there’s a lot of stigmas around clinical trials and are you getting… Are you getting a drug that we don’t know what’s gonna work, am I being…am I being tested? In oncology, I would say for the most part, we try to make trials where you’re being measured to the standard, so you’re getting the standard plus, or we’re trying not to…just in terms of doing what’s best for the patient, in general, I don’t offer trials to patients where I don’t think that there’s scientifically a rationale for those drugs, but to answer your question, the best place to look is on clinicaltrials.gov. That’s cumbersome. If you don’t know what you’re looking for, I can give you a lot of unnecessary information. There are a lot of other resources out there, The Leukemia & Lymphoma Society is a great resource. I know that they have online or people that you can talk to in terms of helping you direct specific clinical trials, I know depending on where you live in the country, there are other local New Chapters, oncology chapters that we have that can help patients find…

And have access to clinical trials, and then I think the biggest thing is just if a patient is with the community oncologist, having enough education to say, can I have a referral to an academic institution where they can ask those questions and get that information, and local community oncologists are fantastic, but they see everything, they see breast cancer, they see one cancer where the academic centers were specialized where all I see is leukemia and MDS kind of acute leukemias. So it’s just a different set of knowledge.

Sasha Tanori:

Okay, my next question is, I’ve had one telemedicine visit via my online portal, is the role of the telemedicine in AML care becoming more important?

Dr. Catherine Lai:

Yes, so what I would say…so this is my personal opinion, but in my opinion, that medicine compared to other industries tends to be a little bit farther behind, we’re not as quick to adapt the newest technology where COVID has helped, I think is at least in my practices, help utilize telehealth in the sense that there was a period of time where I was seeing fewer patients and then it really picked up because especially for patients who have a local oncologist but want a second opinion, the telehealth really offers that they don’t have to travel two hours to come see me to get that opinion. So what I would say is that it cannot replace the physical exam, it can’t replace a face-to-face discussion when you’re really talking about new diagnosis and therapy, because I really do think that that should be in person, but where… I have found that it’s been really helpful is if I’ve had an initial visit with the patient, and they either have a local oncologist, so I’m just checking in with them periodically, or if it’s to review results, say they’ve had a bone marrow biopsy and it’s…

They’re further along in their treatment, or if they’re just reviewing imaging results or something where I don’t necessarily need to see them have a physical exam and I’ve seen them recently, and so I do everything else that’s going on, but can I check in to review a specific part of information. I think that telehealth would have a role, and I hope it continues to have a role.

Sasha Tanori:

Yeah, yeah definitely, I agree. It’s really helpful in that sort of way, so you don’t have to actually leave the comfort of her home for something that’s not really super serious. You know?

Dr. Catherine Lai:

Exactly, yeah, I think what happens is patients do tend to…what I’ve noticed patients do is under-report, so it’s for… Not for infrequent visits, so for patients who are followed on a regular basis, it does allow there to be some ease of burden in terms of how we treat our patients.

Sasha Tanori:

Right. So a silent side effect that people facing cancer don’t always talk about is mental health. Are there any treatments or coping methods that you recommend for patients and care partners?

Dr. Catherine Lai:

Yeah, so I would say to get social work involved early on, I think there’s also…it’s silent, ’cause there’s a lot of stigma around it, is that is something that we should be talking about or not talking about or…I can handle it, that sort of thing, so I introduce our social worker very early to know that she is a resource for the patients, no matter how big or how small, just to try to get them used to that idea. What I would also say is just talking with as many people as possible as I’m sure you realize that the network and the community is small and everybody is willing to help each other out, so once you put yourself out there, you’ll realize that there are other resources out there, and you’re not alone in this journey, and what your cancer team offers you is different than what other patients who have gone through exactly what you’ve gone through can offer, and so I know that there are other resources out there in terms of societies that connect other patients who have the same diagnosis, so I would say it’s really just about education and talking and knowing that it’s okay to talk about your diagnosis and no matter what format that is, or if it’s a little bit now and a little bit later, and also just normalizing it, in the sense of the feelings you have are valid and normal, and if you don’t have those feelings is actually when I get worried about patients because you’re supposed to have certain reactions, you were a young patient and you were diagnosed with cancer.

That’s not a trivial thing. And we’re just…we’re all here to help you and help the patients go through everything…

Sasha Tanori:

So for my last question is the future bright in AML treatment and can you speak about any exciting studies that you are working on, that AML patients and their families should stay tuned for?

Dr. Catherine Lai:

Yes, so I am excited. I am excited to say that I think in my lifetime, I will be a part of AML change and we have already seen it. I have mentors who are in their 60s, who have used the same therapies, they use them for the entirety of their career. And so as I mentioned, we only have your 9 FDA approvals. I think there are more coming… I think what I would like to mention is I think the use of immunotherapy, bone marrow transplant is the original immunotherapy, but as you know, there are many risks and benefits and complications, and so how we manipulate the immune system or how we use drugs to help manipulate the immune system, I think it’s a work in progress. It has been more successful in other cancers, not as successful in AML yet, but I think we will get there. The other thing would be, is how… We look at minimal residual disease. So, as you know, but for everybody else, we consider a complete remission is less than anything less than 5 percent blast or 5 percent leukemia cells but we know that anything greater than zero is bad, and you have more than zero, the disease will come back at some point.

So looking to how we monitor, going back to those molecular technologies and how we’re monitoring for residual disease so that we can detect disease faster, so I think really the concept of detection and prevention will come into a huge role because also if we can detect the disease relapse sooner, we’re treating less disease and then there’s less side effects and less toxicity, and then I think the last thing would be health outcomes of a lot of what we’ve been talking about just in terms of the whole picture and how we can better treat these patients I also think there’s a huge role for looking at each individual person and their age and their medical problems, and they’re a physiologic age as opposed to their chronological age and how we can best treat the patient so they can have the best outcome.

Sasha Tanori:

All right, well, thank you so much, Dr. Lai, for taking the time to speak with me and for all you’ve done for the AML community and our patient’s families, everyone.

Dr. Catherine Lai:
Thank you, thank you so much for having me. I’ve really appreciated you putting yourself out there… Thank you.

What Treatments Are on the Horizon for Acute Myeloid Leukemia Patients?

What Treatments Are on the Horizon for Acute Myeloid Leukemia Patients? from Patient Empowerment Network on Vimeo.

What can acute myeloid leukemia (AML) patients expect in the future of AML studies? Watch as expert Dr. Catherine Lai shares insight about the state of FDA approvals. what is in pipeline for AML treatment, and disease monitoring technologies for improved patient care.

See More from Best AML Care No Matter Where You Live

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Are Acute Myeloid Leukemia Patients at Risk for Secondary Cancers?

Are Acute Myeloid Leukemia Patients at Risk for Secondary Cancers? 


Transcript:

Sasha Tanori:

Is the future bright in AML treatment, and can you speak about any exciting studies that you are working on, that AML patients and their families should stay tuned for?

Dr. Catherine Lai:

Yes, so I am excited. I am excited to say that I think in my lifetime, I will be a part of AML change and we have already seen it. I have mentors who are in their 60s, who have used the same therapies, they use them for the entirety of their career. And so, as I mentioned, we only have your nine FDA approvals. I think there are more coming…I think what I would like to mention is I think the use of immunotherapy, bone marrow transplant is the original immunotherapy, but as you know, there are many risks and benefits and complications. And so how we manipulate the immune system or how we use drugs to help manipulate the immune system, I think it’s a work in progress. It has been more successful in other cancers, not as successful in AML yet, but I think we will get there. The other thing would be, is how…we look at minimal residual disease. So, as you know, but for everybody else, we consider a complete remission is less than anything less than 5 percent blast or 5 percent leukemia cells but we know that anything greater than zero is bad, and you have more than zero, the disease will come back at some point.

So looking to how we monitor, going back to those molecular technologies and how we’re monitoring for residual disease so that we can detect disease faster, so I think really the concept of detection and prevention will come into a huge role because also if we can detect the disease relapse sooner, we’re treating less disease and then there’s less side effects and less toxicity, and then I think the last thing would be health outcomes of a lot of what we’ve been talking about just in terms of the whole picture and how we can better treat these patients I also think there’s a huge role for looking at each individual person and their age and their medical problems, and they’re a physiologic age as opposed to their chronological age and how we can best treat the patient so they can have the best outcome.