Tag Archive for: BCMA

What Emerging Myeloma Treatments Are Showing Promise?

What Emerging Myeloma Treatments Are Showing Promise?  from Patient Empowerment Network on Vimeo.

Myeloma specialist Dr. Mark Schroeder reviews the latest advances in myeloma treatment, including a discussion of CAR T-cell therapy and bispecific antibodies.

Dr. Mark Schroeder is a hematologist at Siteman Cancer Center of Washington University School of Medicine in St. Louis. Dr. Schroeder serves as Associate Professor in the Department of Medicine. Learn more about Dr. Schroeder.

See More from Engaging in Myeloma Treatment Decisions

Related Resources:

Multiple Myeloma Clinical Trials: Which Patients Should Participate

Expert Perspective Advances in Treating Relapsed and Refractory Myeloma

How Does Disease Staging Affect Myeloma Treatment Choices?

Transcript:

Katherine Banwell:

What about emerging therapies for myeloma? What approaches are showing promise? 

Dr. Mark Schroeder:

So, I think the biggest news in myeloma, and across a lot of cancers now, are immunotherapies. We know in myeloma – now we have two CAR T-cells –  

Now a CAR T-cell is engineering your own immune cell called a T cell to express a receptor on its surface that binds to the myeloma, and then those immune cells go and kill the myeloma. That’s a form of immunotherapy.  

There’s two CAR-T cells for treating myeloma after the myeloma has come back four times, has needed four treatments. Those are very active in that line of therapy, and we can see response rates over 80 percent in patients who otherwise weren’t responding to other approved therapies for myeloma.  

On the other hand, there are other immunotherapies that are used earlier in the treatment course of myeloma. One that is not incorporated more frequently for the initial treatment is a drug called daratumumab – it’s an antibody. It’s a protein that binds to the surface of myeloma and stimulates the immune system to react against the myeloma. And so, it’s not a traditional chemotherapy, but it’s using your own immune system to attack the cancer.  

And then a third one that’s probably just as – it looks just as potentially effective as CAR-T cells are called bispecific antibodies. And that would use a protein similar to daratumumab which is an antibody, but it uses parts of antibodies to bind to – it could be two different proteins – one expressed on a T cell, the other one expressed on the myeloma cells. And when it binds, it brings those two cells together and causes your own immune system to attack the myeloma. Those are also very effective, and within the next month or two, there will be a bispecific antibody approved for treating patients with myeloma. 

Katherine Banwell:

Oh, that’s great news. Any others? 

Dr. Mark Schroeder:

Yeah, well – I mean, the other potential – there are other immune cells called natural killer cells that are also in clinical trials for development to attack myeloma, and potentially even engineering those natural killer cells to attack myeloma.  

There are other antibodies; sometimes the antibodies of protein bind a specific target on the surface of the myeloma. I mentioned one – daratumumab – but there is a whole list of others that are in clinical development. The one other antibody – or two, couple of other antibodies that are approved for treating myeloma are isatuximab which also binds to CD38. And another one called elotuzumab which binds to a protein called CS1 or SLAMF7 on the surface of myeloma.  

That’s more information than you probably wanted or needed, but those antibody therapies can be very effective in treating myeloma. There is another antibody therapy that has a payload of a toxin on the antibody, and it binds to BCMA or B-cell maturation antigen.  

That’s the same antigen that the bispecific antibodies as well as the CAR-T cells are targeting on myeloma surface, and so that is potentially one that is approved by the FDA also to treat myeloma.   

Katherine Banwell:

As we close out our conversation, Dr. Schroeder, I wanted to get your take on the future of myeloma. What makes you hopeful? 

Dr. Mark Schroeder:

Well, I am hopeful – just within the last five years, there have been a number of new drugs approved for myeloma. They are approved for later lines of therapy, but they are being moved earlier in the treatment. And within the last 10-20 years, we’ve seen an improvement in the survival of patients with myeloma. As these new therapies are in development, as they’re being moved earlier in the treatment line, I’m very hopeful that survival and potentially cure for this cancer is possible. The only way that we’re going to get to that point is through clinical research and for patients to partner with their physicians and to consider clinical trials because that is the only way that new drugs get approved and are available to other patients with myeloma. So, I’m excited about what is approved; I’m excited about what’s coming through the pipeline to treat myeloma.  

Expert Perspective: Advances in Treating Relapsed and Refractory Myeloma

Expert Perspective: Advances in Treating Relapsed and Refractory Myeloma from Patient Empowerment Network on Vimeo.

Dr. Abdullah Khan, of Ohio State University Comprehensive Cancer Center – The James, reviews currently available treatments as well as those in development for patients with relapsed or refractory myeloma. 

Dr. Abdullah Khan is a hematologist specializing in multiple myeloma and plasma cell disorders at the Ohio State University Comprehensive Cancer Center – The James. Dr. Khan is also an assistant professor in the Division of Hematology at The Ohio State University. Learn more about Dr. Khan.

See More from Engaging in Myeloma Treatment Decisions

 

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How Does Disease Staging Affect Myeloma Treatment Choices?

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Relapsed and Refractory Myeloma Defined

Transcript:

Katherine:

Are there any recent advances in treatment for patients with relapsed or refractory disease?  

Dr. Khan:

Currently and in the past 20 years or so, we’ve seen about 20 approvals for new drugs for patients with multiple myeloma. The way the approval process works it typically looks at the effectiveness of a drug in the relapsed refractory setting first. And after establishing the safety and efficacy, the therapies are moved earlier in the disease course.   

The great example of this are the anti-CD38 monoclonal antibodies daratumumab and isatuximab. They were first approved in the relapsed refractory setting in combination with other antimyeloma treatments. And due to their impressive effectiveness and relative safety, they’re already being used in the frontline setting for patients with newly diagnosed multiple myeloma.   

In the newly diagnosed setting, a commonly cited study is the phase two GRIFFIN trial. And that added daratumumab to the BRd, or bendamustine (Bendeka, Treanda), lenalidomide (Revlimid), dexamethasone backbone.  

And Europe, they completed the phase three study of adding isatuximab, the other anti-CD38 monoclonal antibody to the BRd backbone. And what we’re finding what was very effective in the relapsed refractory setting was actually adding to the efficacy of newly diagnosed treatment regiments. As a side note, these trials – there are also trials looking at daratumumab and isatuximab in the smoldering myeloma phase, so moving it even earlier.  

I think one of the most attractive new targets in myeloma is targeting this antigen called B-cell maturing antigen, and a number of therapies are being developed or are already developed for it. The first approved was belantamab mafodotin, and this is an antibody drug conjugate. 

So, when the antibody binds to BCMA on the multiple myeloma cells, it releases its toxic payload into the myeloma cell. And so, it’s very effective towards myeloma, and no other good cells or fewer other good cells are affected by it. To provide some numbers, in patients with a median of seven prior lines of treatments, meaning their myeloma had relapsed that many times, the response rate was about 30 percent. And a fifth of those patients had VGPR, very good partial response, or better response.  

There are also bispecific antibodies that target this myeloma marker, and we anticipate getting one approved soon in the U.S. called teclistamab. Teclistamab is an antibody that binds both CD3 on T cells of the immune system and B-cell maturating BCMA on the myeloma cells. 

So, the way this antibody kills myeloma is by activating the T cells, the immune system, and directly killing the tumor. So, this was recently published in the New England Journal of Medicine. And in people who were treated with at least five prior lines of therapy, the response rate was about 63 percent, and the median progression-free survival, or the time until the myeloma progressed, was about 11 months.  

We were very active in a clinical trial looking at the effectiveness of another antibody, a bispecific antibody, called Regeneron 5458. In a similar patient population, the response rates were 75 percent in the higher-dose level group, and right now it’s actually a bit too early to tell how long the progression free survival is or the duration of response. 

There are also other bispecifics in development targeting other myeloma markers ssuch as talquetamab, that binds to a marker called GPRC5D, and cevostamab, which binds to a marker called FcRH5. The response rates as single agents in patients with relapsed refractory multiple myeloma are 66 percent and 45 percent respectively. These are all incredible numbers for a single drug in the relapsed refractory setting.  

How Is CAR T-Cell Therapy Changing Myeloma Care?

How Is CAR T-Cell Therapy Changing Myeloma Care? from Patient Empowerment Network on Vimeo.

Dr. Abdullah Khan discusses how CAR T-cell therapy works to treat myeloma, the currently approved CAR T-cell therapies, and the outcomes related to progression free survival (PFS) for patients with heavily pre-treated myeloma.

Dr. Abdullah Khan is a hematologist specializing in multiple myeloma and plasma cell disorders at the Ohio State University Comprehensive Cancer Center – The James. Dr. Khan is also an assistant professor in the Division of Hematology at The Ohio State University. Learn more about Dr. Khan.

See More from Innovative Myeloma Therapies

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Immunotherapy: Which Patients Is It Right For?

How Is CAR T-Cell Therapy Changing the Myeloma Treatment Landscape?

How Is CAR T-Cell Therapy Changing the Myeloma Treatment Landscape?

What Are the Risks of CAR T-Cell Therapy?

Transcript:

Katherine:

Let’s talk about CAR T-cell therapy. How is CAR T-cell therapy changing the field?  

Dr. Khan:

Myeloma was a little late to the CAR-T game, but we’re very happy it’s here. The two products approved in myeloma are idecabtagene vicleucel, ide-cel for short, and ciltacabtagene autoleucel, or cilta-cel for short. 

So, the way CAR Ts work, they are customized T cells for each individual patient. You collect the T cell from the patient with myeloma. You reengineer them in the laboratory to produce proteins on their surface called chimeric antigen receptor. That’s CAR portion of the CAR T therapy. And these CARs recognize and bind specific proteins on the surface of multiple myeloma.  

So, these genetically modified T cells are then expanded or multiplied to make millions of cells. They’re sent back to the hospital where they were collected, where the patient is. And they’re infused back into the patient. The hope is that these modified cells, these CAR T cells, will continue to multiply in the patient. And with guidance from that engineered receptor, they will recognize and kill multiple myeloma very effectively. 

So, I can provide some numbers to the outcomes of the two approved CAR T cells – CAR T products in multiple myeloma. The first approved was ide-cel in patients with a median of six prior lines of therapy, a single dose of CAR T was able to produce an objective response rate – that’s how many people responded to the treatment – of 73 percent, and the median, the middle person, progressed after 8.8 months of getting this treatment. The other product, cilta-cel, was also studied in patients with a median of six prior lines of therapy, and the objective response rate was an astounding 98 percent.  

Katherine:

Wow.  

Dr. Khan:

And the median progression-free survival is actually not yet reached. So, these are remarkable results with heavily pre-treated myeloma. And the myeloma community’s very excited to actually bring these treatments to earlier lines of therapy such as a newly diagnosed patient with multiple myeloma. 

Advances in Myeloma Molecular Testing

Advances in Myeloma Molecular Testing from Patient Empowerment Network on Vimeo.

What is molecular testing, and how does it impact myeloma care? Dr. Abdullah Khan from the Ohio State University Comprehensive Cancer Center – The James discusses the specific markers found in cytogenetic analysis that determine a patient’s risk and may impact treatment choices.

Dr. Abdullah Khan is a hematologist specializing in multiple myeloma and plasma cell disorders at the Ohio State University Comprehensive Cancer Center – The James. Dr. Khan is also an assistant professor in the Division of Hematology at The Ohio State University. Learn more about Dr. Khan.

See More From INSIST! Myeloma

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How Do Test Results Impact Myeloma Treatment Options?


Transcript:

Katherine:

Have there been advances in molecular testing for myeloma patients?  

Dr. Khan:

Molecular testing is a broad term and can indicate checking genes, proteins, and other molecules. Even let’s say speaking outside of the world of myeloma, molecular testing can be used to determine in individuals if they have a high chance of developing cancers or other diseases.  

It can be done to confirm so cancer diagnoses using the tissue biopsy specimens. It can also be used to help plan treatment, find out how well the treatment is working, provide prognosis information, and other information. In the world of myeloma, there are – in the world of myeloma, there are researchers looking at all of these molecular changes that can happen with disease.  

Katherine:

So, how do the results of these tests affect treatment?  

Dr. Khan:

There’s a particular cytogenetic change called translocation 11;14 that’s found in maybe a quarter of all patients with newly diagnosed myeloma, and it predicts a high likelihood of responding to a new drug called venetoclax.  

In the clinical trial of venetoclax, when it was given to all patients with multiple myeloma, there was actually higher mortality in patients when given venetoclax in combination with bortezomib and dexamethasone. And this is despite a higher response rate by adding the venetoclax.  

The thought process was maybe those patients were not doing well because of higher chances of serious infections. But when they took the data and they looked at that subgroup of patients with the translocation 11;14, there was no such concern in that subgroup. So, in this case of having translocation 11;14, it actually giving you a new treatment option based on the findings of the molecular testing. 

We participate in a national clinical trial called MyDRUG, and that’s looking at other molecular changes to see if a more targeted treatment when added to the backbone of myeloma therapies translates to better outcomes.  

Another recent development in molecular testing is diagnostic testing for minimal residual disease, and that’s from the bone marrow in patients with multiple myeloma.  

The most commonly used test in clinical trials is the clonoSEQ test; it’s an FDA-cleared diagnostic test. The way it works it looks for specific DNA sequences on the receptors of the cancer cells. So, each cancer cell has like a genetic barcode.  

Using the liquid part of the marrow, we can look for those cells that harbor that genetic barcode. 

And the test is so sensitive, we can find one in a million cells in a patient’s bone marrow aspirate. So, it’s a very sensitive test, but it is not yet approved for making treatment decisions. One way we can use it though is for prognostic information. So, a patient attaining minimal residual disease-negative status or MRD-negativity, probably will do better than someone who has MRD-positive disease.  

And there’s an emerging concept called sustained MRD negativity. So, let’s take an example of someone getting MRD testing at one year and two years after their stem cell transplant. The patient who is MRD-negative at both the one-year and two-year marks will likely do better than the one who is MRD-negative at one year but turns positive at the two-year mark. 

So, these are some of the new developments in molecular testing in multiple myeloma.  

Making Myeloma Treatment Decisions at Every Stage of Care

Making Myeloma Treatment Decisions at Every Stage of Care from Patient Empowerment Network on Vimeo.

Dr. Mark Schroeder, of Siteman Cancer Center, reviews the types of treatment approaches available for patients with myeloma, discusses how therapies are chosen and why, including in the relapsed and refractory setting. Dr. Schroeder also shares an update on new and emerging myeloma therapies.

Dr. Mark Schroeder is a hematologist at Siteman Cancer Center of Washington University School of Medicine in St. Louis. Dr. Schroeder serves as Associate Professor in the Department of Medicine. Learn more about Dr. Schroeder, here.

See More from Engaging in Myeloma Treatment Decisions

Download Resource Guide

 

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The Role of a Myeloma Specialist on Your Care Team

How Is a Myeloma Patient in Active Treatment Monitored?

Transcript:

Katherine Banwell:

Hello, and welcome. I’m Katherine Banwell, your host for today’s webinar. Today’s program is about how to actively engage in myeloma treatment decisions at every stage of your care. 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. Well, let’s meet our guest today. Joining us is Dr. Mark Schroeder. Dr. Schroeder, welcome. Would you please introduce yourself?  

Dr. Mark Schroeder:

Yeah. Hi, Katherine. Thanks for having me. I’m Dr. Mark Schroeder. I’m an Associate Professor of Medicine at Washington University School of Medicine in St. Louis. 

Katherine Banwell:

Thank you so much for taking the time out of your day to join us. As I mentioned, this webinar is about actively engaging in myeloma care decisions. So, I’d like to start with this important question, why is it essential for patients to play a role in their care and treatment decisions? 

Dr. Mark Schroeder:

Yeah, I mean patients are – a patient should be actively involved in decisions with their doctor. As a physician, doctors are thinking about “What is the best treatment for their disease or their cancer?” and patients, I think, have a role in trying to guide the doctor in terms of what outcomes they are seeking from treatment, what is there lifestyle like that we could potentially guide treatment around. Patients have different goals. Sometimes in cancer, we’re going for curative therapies. Sometimes we’re not, and quality of life is more important. Having an actively engaged patient ensures that your doctor is trying to tailor treatment to you.  

The patient who is educated also helps to bring resources to their physician about – sometimes physicians may not know of all the clinical trials that are ongoing or potentially even therapies. But have a patient ask about certain studies or ask about certain therapies, it helps to open a conversation with your physician to discuss those and to kind of talk through why it may or may not be a good idea for them in particular. 

Katherine Banwell:

Well, thank you. That helps guide us as we begin our conversation. As a patient, engaging in your care starts with understanding your diagnosis, so I’d like to go through some definitions. What is multiple myeloma? 

Dr. Mark Schroeder:

Multiple myeloma is a blood cancer. It’s a cancer in particular of a blood cell called a plasma cell. Everybody has normal plasma cells in their body. It’s part of your immune system that responds to infections; they are also cells that respond to vaccinations.  

And when a plasma cell becomes a cancer, it often forms a cancer called multiple myeloma. And that cancer results often times in damage to bones, low blood counts or anemia, potentially kidney problems, or possibly seeing high levels of calcium.  

Katherine Banwell:

What about smoldering myeloma? What is that? 

Dr. Mark Schroeder:

So, smoldering myeloma is a stage that happens prior to the development of myeloma that is causing organ damage. I talked about the damage to bones, kidneys, blood cells – that is called the CRAB criteria. The C stands for calcium, the R renal, A anemia, and B bones. We define myeloma by having damage to one of those four essential systems.  

Smoldering myeloma can happen when we actually see plasma cells that look like myeloma – that look like cancer cells, but they’re not causing the CRAB features of multiple myeloma. And there is a chance that sometimes that smoldering form of myeloma, it’s not causing any damage, but it can evolve and change into myeloma. 

Katherine Banwell:

What is MGUS?  

Dr. Mark Schroeder:

MGUS is a stage that happens prior to smoldering myeloma. We know that MGUS which stands for monoclonal gammopathy of undetermined significance – it’s a mouthful. That’s why we like to say MGUS.  

Katherine Banwell:

Yes. 

Dr. Mark Schroeder:

But it’s a protein that can be detected in your blood. Sometimes that protein does not mean you have a cancer. We can detect proteins like that in blood in patients who have, say, autoimmune diseases, and they’re at low levels. It’s just an immune response; it’s produced by those plasma cells that can be cancerous, but sometimes plasma cells grow because they’re stimulated – they’re overstimulated.  

And so, that monoclonal protein of MGUS can be detected in the blood, but we don’t see an increase in the number of cells in the bones that are classic for myeloma. But we know that about 1 percent of patients who have MGUS, every year, 1 percent might progress on to develop multiply myeloma. So, it’s a risk factor; it’s on the spectrum of disease from MGUS to smoldering myeloma to myeloma.  

Katherine Banwell:

Okay. And how is asymptomatic myeloma monitored?  

Dr. Mark Schroeder:

So, asymptomatic patients, I would consider those are the patients who have smoldering myeloma, so they don’t have the high calcium, the renal issues, anemia, or bone problems. And typically, those patients are followed up about every three to six months, depending on where they fit in kind of that spectrum of MGUS to smoldering myeloma to myeloma.  

Sometimes patients who have clinically identified myeloma and it presents very heterogeneous sometimes. They may not have a lot of organ involvement or organ damage, and maybe they’re frail, they’re elderly. And it may be appropriate also to observe patients who actually have some of the findings of myeloma, but the disease doesn’t seem to be as aggressive. 

Katherine Banwell:

Okay. Let’s talk about the different phases of therapy for myeloma, and I’m going to ask you for some more definitions. What is induction therapy? 

Dr. Mark Schroeder:

Induction therapy is the first treatment that we’re starting for myeloma. It’s oftentimes a combination of a number of chemotherapies that our goal is to get control of the cancer quickly, so reduce the burden of the cancer in a patient’s body.   

Oftentimes, when patients present with myeloma, that’s when the burden of cancer is the highest. So, induction therapy is a combination often of three or four different drugs given over the course of about three to four months to treat the myeloma and get initial control.  

Katherine Banwell:

What about consolidation therapy? What is that?  

Dr. Mark Schroeder:

So, after you have had a response to induction therapy, your oncologist might talk about, “Well, let’s deepen that response.” That’s when we think about consolidation. So, it’s going to be poten – most of the time is a change of therapy from the three or four drugs that you were treated for in the myeloma. An example of consolidation would be going through a stem cell transplant or more chemotherapy after stem cell transplant. So, that’s a change in therapy, and it ends up deepening the response, killing more of the cancer. 

Katherine Banwell:

And what about maintenance therapy?  

Dr. Mark Schroeder:

So, after you have gone through induction, you have control of the myeloma, we’ve deepened that response with consolidation, we know that myeloma is a cancer that tends to come back. And we know from experience that continuing some of the drugs that we used in induction at low doses are effective to try and prevent it from progressing or coming back, and it extends that period of time – and that’s maintenance therapy. It’s using some of the drugs we used to initially treat myeloma at lower doses to continue to suppress low levels of the cancer. 

Katherine Banwell:

Thank you for that. There are a number of treatments for myeloma patients. Can you talk about the types that are available? 

Dr. Mark Schroeder:

Yeah. So, the classes of – actually there is lots of drugs approved for treating myeloma but also recently approved.  

And we classify them into big categories. One of the categories is called immunomodulatory drugs – those are drugs like Revlimid and pomalidomide, or even thalidomide which was one of the first immunomodulatory drugs. Those are oral drugs that work on a specific pathway in the myeloma that leads to the myeloma cell dying. Another class of drugs are called proteasome inhibitors. Those include drugs like bortezomib or carfilzomib. Those drugs are often given under the skin or in the vein, and we know that they work really effectively on their own, but also when we combine them with an immunomodulatory drug like Revlimid or pomalidomide, the effect is even better. Another class is steroids. Steroids are kind of one of the first drugs used to treat this cancer, and steroids are effective at treating myeloma cells.   

Plasma cells are responsive to steroids. One of the first treatment regimens used to treat myeloma were traditional chemotherapies, and those are usually reserved for later on. You might think of traditional chemotherapy that causes hair loss, nausea, vomiting, low blood counts. Those, decades ago, were used to treat myeloma, but now we have effective oral, IV, or injection into the skin that don’t cause a lot of the traditional chemotherapy side effects but are very effective at treating the myeloma. And then another major class of drugs are considered immunotherapies. So, these are treatments that are engineered to either stimulate the immune system to go attack the myeloma, or maybe it’s even using part of your own immune system to engineer it to go attack the myeloma. 

Examples of those are called bispecific antibodies which kind of binds to the myeloma but binds to an immune cell, brings them together, or a CAR-T cell which takes your own T cells genetically modifies them to attack the cancer. 

Katherine Banwell:

And there is also a bone marrow transplant. Is that right? 

Dr. Mark Schroeder:

That’s right, yeah. I neglected – so, bone marrow transplant has been around for a while in myeloma. And despite it being around for so long and really good therapies being approved for myeloma, it’s still a standard treatment for myeloma. And bone marrow transplant in myeloma uses a traditional chemotherapy called melphalan that is associated with the chemotherapy side effects we talked about. But the advantage of bone marrow transplant is that it prolongs the time before the myeloma comes back and needs other treatments, and that’s why we do it. It can be toxic, but it can prolong the time before a patient needs another line of therapy.  

Katherine Banwell:

We know that everyone’s diagnosis is different. So, how do you determine a treatment plan for an individual patient? 

Dr. Mark Schroeder:

So, it depends in terms of the patient – initially, I will evaluate patients and determine how fit they are. Is it a patient that I think is strong enough to undergo a stem cell transplant? Is that going to be a benefit to them? That’s not necessarily a factor of just age, but it’s also, are they doing well functionally, or do they have any other medical problems like heart disease or kidney problems? Those things play into my decision on a treatment initially with patients. So, whether you’re fit or unfit will help to guide what your treatment is going to be in general. Fit patients are somebody that could undergo multiple treatments, go through a transplant, have minimal toxicity, and recover fully after more intensive treatments.  

Whereas, unfit may need more assistance, and we tend to reduce the intensity of treatments. It doesn’t mean the treatments, if you’re unfit, are less effective – they can be very effective. But our goals for treatment change in that situation. And we’re looking for responses but also looking for quality of life. And then it changes also depending on the genetics of the myeloma. Our treatment for patients who have genetic changes that are high risk will change compared to those that have what are called standard risk genetic changes.  

So, that is an important point to discuss with your oncologist if you have – Do I have standard risk or high-risk genetic changes in my cancer? And does that effect my treatment? And then also, treatment in somebody who is being treated a second time or third time or beyond for their myeloma depends on what treatments you had before and how effective they were.  

And what were your toxicities or side effects from those treatments? So, all those factors play into a decision of treatment for an individual.  

Katherine Banwell:

Oh, that’s great information. Let’s discuss what happens after treatment. How is the effectiveness of a treatment monitored? 

Dr. Mark Schroeder:

When you are initially diagnosed with myeloma, we will perform testing of blood. We look for that monoclonal protein or protein in the blood that is produced by the cancer cells. That protein level will be used to monitor the response of the cancer, and that’s a blood test – that’s called a serum protein electrophoresis. Also, initially, we’ll have x-rays of the bones, or it might be a CT scan or an MRI or PET scan that’s used to document if there is any bone damage. And oftentimes when we’re following up, we follow the bloodwork to look for reduction in that protein level.  

We may follow up additional x-rays to see if there are new areas in the bones that are damaged or if prior areas have responded to the treatment. And then oftentimes a bone marrow biopsy is used to document if you are in a complete remission which means that the protein we detected before or the cancer cells in the bone marrow cannot be detected after treatment. 

Katherine Banwell:

Why is it essential for patients to share any symptoms or issues they may be having with their healthcare team during and after treatment? 

Dr. Mark Schroeder:

Yeah, I mean, the treatments for multiple myeloma, they are typically continued in patients, and as we continue these treatments, side effects happen.  And as a physician, we can support patients through side effects. It may be as simple as adding a medicine to help with nausea. It may be modifying the dose of the treatments.  

So, it’s important to kind of monitor for things like, “I’m having a rash or diarrhea” or “I am getting nausea,” and letting us know right away. What the bad outcome would be if a patient is taking a medicine doesn’t let us know about side effects and decides to stop the medicine. Obviously, if you’re not taking a chemotherapy medicine, it’s not going to be effective to treat your cancer. That happens sometimes. So, having a good communication with your physician and your team of medical providers is important so that we can modify treatment. There are lots of alternatives for adjustments in the treatment that can be made that can be just as effective as the treatment you started on. 

Katherine Banwell:

So, communication is key. 

Dr. Mark Schroeder:

Yes. For sure, for sure. 

Katherine Banwell:

If treatment is successful, then when is a patient considered in remission? And what does remission mean? 

Dr. Mark Schroeder:

Remission – there are gradients on remission in myeloma. And we can have a partial remission which means we kill about half of the cancer cells. We can have very good partial remissions, or we can have complete remissions. And those equate to the depth of response or how well the myeloma responded. Those are measured by bloodwork, bone marrow biopsy, and may be repeat imaging or x-rays. So, if you have a complete remission, that means, we can’t detect that protein in the blood that was detected before, or protein that was detected in the urine, and we can’t detect the cancer cells on a bone marrow biopsy. We know that the deeper your remission or response to treatment, that equates typically with a longer time before the cancer may come back or need other therapies.   

Myeloma is a type of cancer that tends to come back, so we have very effective therapies, and sometimes, these therapies can get the myeloma to a state that we can’t detect one in a million cancer cells, but it tends to come back. And so, complete remissions means that, “Yes, it’s a good chance that the myeloma is not going to come back for years for you, but you still need to be monitored. You’re not necessarily cured of the cancer.” 

Katherine Banwell:

Unfortunately, relapse can occur after treatment as you’ve been talking about. And sometimes, a patient’s disease doesn’t respond to therapy, and that’s called refractory disease. What are the indicators that a patient’s disease may have relapsed?  

Dr. Mark Schroeder:

Yeah, so we would typically be following a patient about every three months. Somebody that has gone through the initial induction, consolidation, maybe they’re on maintenance therapy, or maybe they’re on active therapy for after they have relapsed from a myeloma. Each of those visits every three months, we are monitoring bloodwork, we’re monitoring the monoclonal protein that the myeloma produces.  

Or if it doesn’t produce much of that protein, we’re monitoring other parameters, so urine testing or maybe even imaging like a PET scan. And we’re looking for consistent rises in that number, and we’re looking for, not necessarily a little rise in the protein, but incremental continuous rise – that suggests that the myeloma is starting to grow again, and it’s growing on the current treatment, and we need to switch gears and try a different treatment. There are some patients who – that protein, the myeloma or the myeloma cancer doesn’t die to treatments – that’s refractory. So, we try a treatment, and there’s just no response. We don’t see a drop in the protein in the blood, we still see a good burden of the myeloma in the bone marrow biopsy. And those patients, that’s also an indication to try a different treatment.   

Katherine Banwell:

You mentioned that myeloma often returns, so how typical is it for a patient to relapse? 

Dr. Mark Schroeder:

Yeah, I would say that’s the norm for patients with myeloma. There are reports in patients who undergo things like stem cell transplant, that maybe 10 percent of patients might be out 10 years without detection of their myeloma, but that’s not the norm. So, most patients who are diagnosed with myeloma will go through periods of treatment and hopefully periods of remission – the majority go into periods of remission to myeloma where it’s not very active, but the myeloma tends to come back. 

Katherine Banwell:

If a person is relapsed or refractory, how are they typically treated? 

Dr. Mark Schroeder:

So, when they relapse, it depends on their prior treatment. So, if the myeloma is not responding to a drug, then it is, from the physician’s perspective that’s treating you, a good idea to change the type of chemotherapy drug that you’re on. Any time, whether it’s diagnosis or relapse, clinical trials are appropriate to engage with and potentially even use as primary treatment. All clinical studies in myeloma or for cancer in general are typically engineered around active treatments for the cancer. And so, those studies in myeloma when you’re having the cancer relapse, say, early in the course of your cancer, those studies typically are geared to use drugs that are approved by the FDA. Later in the lines of treatment, maybe you’ve had to progress after four lines of treatment, but trying to move them earlier, and they’re very active in the fourth line.  

So, you could potentially have access to an active treatment moved earlier in the treatment through a clinical trial. There is also a long list of other approved myeloma therapies. There is a good handout, I think, through the NCCN for patients for myeloma that lists a lot of the approved myeloma therapies and kind of guides patients. It’s a good resource book that I would point any of the listeners to. 

Katherine Banwell:

Oh, that’s a great idea. Thank you for that. What about emerging therapies for myeloma? What approaches are showing promise? 

Dr. Mark Schroeder:

So, I think the biggest news in myeloma, and across a lot of cancers now, are immunotherapies. We know in myeloma – now we have two CAR-T cells –  

Now a CAR-T cell is engineering your own immune cell called a T cell to express a receptor on its surface that binds to the myeloma, and then those immune cells go and kill the myeloma. That’s a form of immunotherapy.  

There’s two CAR-T cells for treating myeloma after the myeloma has come back four times, has needed four treatments. Those are very active in that line of therapy, and we can see response rates over 80 percent in patients who otherwise weren’t responding to other approved therapies for myeloma.  

On the other hand, there are other immunotherapies that are used earlier in the treatment course of myeloma. One that is not incorporated more frequently for the initial treatment is a drug called daratumumab – it’s an antibody. It’s a protein that binds to the surface of myeloma and stimulates the immune system to react against the myeloma. And so, it’s not a traditional chemotherapy, but it’s using your own immune system to attack the cancer.  

And then a third one that’s probably just as – it looks just as potentially effective as CAR-T cells are called bispecific antibodies. And that would use a protein similar to daratumumab which is an antibody, but it uses parts of antibodies to bind to – it could be two different proteins – one expressed on a T cell, the other one expressed on the myeloma cells. And when it binds, it brings those two cells together and causes your own immune system to attack the myeloma. Those are also very effective, and within the next month or two, there will be a bispecific antibody approved for treating patients with myeloma. 

Katherine Banwell:

Oh, that’s great news. Any others?  

Dr. Mark Schroeder:

Yeah, well – I mean, the other potential – there are other immune cells called natural killer cells that are also in clinical trials for development to attack myeloma, and potentially even engineering those natural killer cells to attack myeloma.  

There are other antibodies; sometimes the antibodies of protein bind a specific target on the surface of the myeloma. I mentioned one – daratumumab – but there is a whole list of others that are in clinical development. The one other antibody – or two, couple of other antibodies that are approved for treating myeloma are isatuximab which also binds to CD38. And another one called elotuzumab which binds to a protein called CS1 or SLAMF7 on the surface of myeloma.  

That’s more information than you probably wanted or needed, but those antibody therapies can be very effective in treating myeloma. There is another antibody therapy that has a payload of a toxin on the antibody, and it binds to BCMA or B-cell maturation antigen.  

That’s the same antigen that the bispecific antibodies as well as the CAR-T cells are targeting on myeloma surface, and so that is potentially one that is approved by the FDA also to treat myeloma.  

Katherine Banwell:

Okay. Let’s go to some audience questions. PEN community member, Mark, sent in this question prior to the program, “When is the right time for a clinical trial? When everything else is refractory?” 

Dr. Mark Schroeder:

No, I think clinical trials should be – you should engage your oncologist to talk about clinical trials right from the beginning. We typically think about clinical studies – they could be interventional where we’re actually giving a treatment. Some clinical trials are observational where we’re trying to learn about disease course in response to traditional therapies. Either of those may have direct benefit to the patient, or maybe it doesn’t affect the patient, but it affects future patients with myeloma.  

There are clinical studies like I mentioned that are moving therapies that are approved, but they’re approved after patients have been treated four or five times for their myeloma, and they’re now being moved earlier in the treatment. Some of those are at the initial treatment of myeloma in that induction phase. And so, we think that maybe by using some of these newer therapies or that immunotherapy class earlier on in the treatment of myeloma could result in deeper responses. We don’t know if it’s going to result in cures or that long remission beyond five or 10 years, but that’s the hope. If we can move the therapies earlier and prevent the cancer from becoming resistant to multiple treatments, maybe we can lead to longer remissions and longer survival of cancer patients. So, engage with your oncologist from the beginning through all of your treatment lines about clinical trials, is what I would say.  

Katherine Banwell:

Well, how can patients find out about clinical trials and what might be right for them? Where should they start?  

Dr. Mark Schroeder:

I mean, starting with your physician and having that conversation is a good start, but there are resources for patients. The Multiple Myeloma Research Foundation MMRF has good resources. There is a – called Myeloma Crowd that also has resources for patients with myeloma and social support for patients with myeloma to try to find and match you with a clinical trial. And then if you’re really academic and interested in doing your own homework online, all clinical studies in the United States, even internationally, are registered on a website called clinicaltrials.gov. Clinicaltrials.gov is – it can be searched, so you can search for myeloma; you can search for a specific drug.  

That will tell you, where are the studies being done, who are the study personnel, who should I contact to find out about the study? Unfortunately, not everybody can travel for treatment for their myeloma, and the best chance of potentially participating in a research study is to initially talk with your oncologist about it. There may be a larger center nearby that you can visit to consider clinical trials.  

Clinical trials that are trying to use the new immunotherapies would be a great option, but they may not be offered in, say, a community oncology practice. You have to have the infrastructure to conduct those studies. And if you have the resources to be able to travel, then finding something on clinicaltrials.gov and – I’ve had patients do the legwork and talk with their local oncologist and get referred to a center that actually has a study that they’re interested in participating.  

But a lot of times, studies are going to have you visit the center for all the screening tests and all the procedures for study. 

Katherine Banwell:

Right, so you have to know that you have the time available as well as the resources. 

Dr. Mark Schroeder:

Right, and the resources to do it. Yeah.  

Katherine Banwell:

Yeah. Trevor had this question, Dr. Schroeder, “My myeloma is considered high-risk. What treatment options are available to me, and are there clinical trials specifically for high-risk disease?” 

Dr. Mark Schroeder:

Yeah, great question. High-risk myeloma happens in about a quarter of patients, so one in four patients will have high-risk myeloma at the diagnosis. And it’s important because we know that when we say high-risk, that means that the myeloma is going to potentially come back sooner after treatments. It doesn’t mean that the treatment you’re going to be given is less effective, but it has a high propensity to come back sooner.  

Those patients with high-risk myeloma still benefit from a lot of treatments that we have for myeloma, but there are clinical trials geared to try and increase treatment in patients with high-risk myeloma to try to change the fact that their cancer comes back sooner than somebody who doesn’t have the high-risk features by using a novel chemotherapies or novel drugs to try to improve responses. So, there are for sure clinical studies, either at – potentially at initial diagnosis or at the time of relapse that could be entertained for patients with high-risk myeloma. And I would encourage you to seek those out for sure.  

Katherine Banwell:

Yeah. Great. Thank you. And please continue to send in your questions to questions@powerfulpatients.org, and we’ll work to get them answered on future programs. As we close out our conversation, Dr. Shroeder, I wanted to get your take on the future of myeloma. What makes you hopeful? 

Dr. Mark Schroeder:

Well, I am hopeful – just within the last five years, there have been a number of new drugs approved for myeloma. They are approved for later lines of therapy, but they are being moved earlier in the treatment. And within the last 10-20 years, we’ve seen an improvement in the survival of patients with myeloma. As these new therapies are in development, as they’re being moved earlier in the treatment line, I’m very hopeful that survival and potentially cure for this cancer is possible. The only way that we’re going to get to that point is through clinical research and for patients to partner with their physicians and to consider clinical trials because that is the only way that new drugs get approved and are available to other patients with myeloma. So, I’m excited about what is approved; I’m excited about what’s coming through the pipeline to treat myeloma.  

Katherine Banwell:

Dr. Schroeder, thank you so much for taking the time to join us today. 

Dr. Mark Schroeder:

You’re welcome, Katherine. It was a pleasure.  

Katherine Banwell:

And thank you for 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 today. 

Key Factors That Guide Myeloma Treatment Decisions

Key Factors That Guide Myeloma Treatment Decisions from Patient Empowerment Network on Vimeo.

Treatment for myeloma varies from one patient to the next. Dr. Joshua Richter, a myeloma specialist, reviews the factors that are considered when choosing a treatment approach.

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.

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Transcript:

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 (Venclexta) 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 lenalidomide (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 pomalidomide (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. 

Myeloma Research | CAR-T Cell & Bispecifics Study Updates

Myeloma Research | CAR-T Cell & Bispecifics Study Updates from Patient Empowerment Network on Vimeo.

Myeloma expert Dr. Joshua Richter reviews the latest updates in myeloma research from the 2022 American Society of Clinical Oncology (ASCO) annual meeting and the European Hematology Association (EHA) Congress.

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


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


Transcript:

Katherine:

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:

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. 

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 Are the Side Effects of Myeloma Immunotherapy?

What Are the Side Effects of Myeloma Immunotherapy? from Patient Empowerment Network on Vimeo.

Myeloma specialist and researcher Dr. Krina Patel discusses the common side effects of immunotherapy and reviews tools that may be used to prevent complications.

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?

Myeloma Treatment & Research Updates From 2022 ASCO and EHA Meetings

Transcript:

Katherine:   

Are there other side effects that patients should know about and side effects that they might experience?

Dr. Patel:  

Yeah, so neurotoxicity is one that we don’t see as much as we see in lymphoma patients, which is again great but sometimes people can get something called ICANS, which is a type of neurotoxicity in the first 30 days after CAR T.

And basically, it can be as bad as seizures, but thankfully we don’t see that very often, or I haven’t seen it at all. But it can cause confusion. It can cause people to be extra sleepy. So, we have different treatments that we give to turn that around. Longer term, really, the big side effects are the counts being low. So, what we call cytopenias. So, white count, hemoglobin, platelets.

And so, that is something we see quite often in our patients who have had a lot of therapy for myeloma already, and then are getting something like CAR T.

So, a lot of my patients will still need transfusions even a month or two or three after, and we’re giving GCSF to help their white count come back up, et cetera.

Katherine:    

What’s that?

Dr. Patel: 

So, G-CSF is basically a growth factor that helps your neutrophil; so, a different type of white blood cell – come back up, which helps fight against bacterial infections.

So, it’s the same medicine for anyone who’s had a stem cell transplant. It’s the same medicine you get to get your stem cells into your blood but it’s at a lower dose. But again, it’s to avoid infections, to help present bacterial infections. The other one is infections can also be caused because of low IgG levels or what we call immunoglobulins; these are our antibodies that we have.

And the good news is, when CAR Ts or bispecifics or some of these immune therapies work really well, they’ll kill as many myeloma cells as we possibly can.

But they also kill good cells. So, they kill good plasma cells that make us antibodies and good B cells that make us antibodies. So, when that happens, people’s IgG levels will go down and that puts you at risk for infection too. So, we actually aggressively give people IVIG to help prevent those infections.

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

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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


Related Programs:

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.