Tag Archive for: refractory myeloma

What Factors Shape Myeloma Treatment Options After Relapse?

/in , , , , , , , /by

What Factors Shape Myeloma Treatment Options After Relapse? from Patient Empowerment Network on Vimeo.

What myeloma treatment options are there for patients who relapse? Expert Dr. Sikander Ailawadhi from Mayo Clinic explains patient factors that must be considered in treatment options and how treatment options may be impacted.

Download Guide  |  Descargar Guía

See More from START HERE Myeloma

Related Programs:

Myeloma Treatment Timing: Prior Therapies and FDA Approval Rationale

 Navigating Myeloma CAR T-Cell Relapse: Patient Next Steps

 How is Treatment Fitness Determined in Multiple Myeloma?

Transcript:

Lisa Hatfield:

For those who relapse for the first time, what are the best treatment options?

Dr. Sikander Ailawadhi:

I think that’s a very important, and I can imagine a scary situation. So somebody who relapses in general, not just even the first time, the factors that are taken into account for deciding what treatment they should get, there are broadly three categories of factors. Patient factors deciding what’s the age, what’s the other comorbidities, are they diabetic, are they heart disease, kidney dysfunction, because those things go into the decision of what may or may not be given. So patient factors.

Also importantly, how close are you to your treatment center? Can you come in for infusional or injection drugs time? And again, can you prefer or do you prefer oral drugs only? Et cetera. Those things become important. Then that…so that’s patient factors and disease factors. How fast is the progression? Is it high-risk disease, standard risk disease? Is it biochemical progression like the previous person asked?

Or is it actually a clinical progression in which there’s kidney dysfunction or anemia or bone disease? Because the choices and the urgency of treatment may change. So patient factors, disease factors, and then drug factors are the third class or third category, which is what have you had before? How long have you been on it? Are you on maintenance or not? Is your disease considered refractory to a certain agent, meaning resistant to a certain agent?

Typically, if you were on a treatment and your disease is progressing, that same drug may not be used again. And there are some times that we will reuse a drug, but generally not. We can use the same class, but we may not typically use the same drug. So I think the choice of treatment depends on all of those factors put in. And then we come up with one or two or three regimens and we discuss them with patients. And, of course, being an academic, physician, I must say there is always, you must always seek out good clinical trials if they’re available to you. That is the way our field moves forward.

Share Your Feedback:

Create your own user feedback survey

Making Treatment Decisions | Understanding Common Myeloma Therapies

/in , , , , , , , /by

Making Treatment Decisions | Understanding Common Myeloma Therapies from Patient Empowerment Network on Vimeo.

What are common myeloma therapies, and when are they used? Dr. Ashley Rosko outlines the factors that impact treatment decisions and reviews available therapies including stem cell transplant, proteasome inhibitors, immunomodulatory therapies, and monoclonal antibodies.

Dr. Ashley Rosko is Medical Director of the Oncogeriatric Program at the Ohio State University Comprehensive Cancer Center – The James. Learn more about Dr. Rosko.

Download Resource Guide

See More From INSIST! Myeloma

Related Programs:

How Close Is Personalized Medicine for Myeloma?

How Close Is Personalized Medicine for Myeloma?

How Do Myeloma Test Results Influence Prognosis and Care?

How Do Myeloma Test Results Influence Prognosis and Care?

 Advances in Myeloma Treatment: CAR T-Cell Therapy and Bispecific Antibodies

Advances in Myeloma Treatment | CAR T-Cell Therapy and Bispecific Antibodies

Transcript:

Katherine:

We know that multiple myeloma patients have a number of options and that many available therapies are used in combination. 

So, I’d like you to walk us through the options that are available. 

Dr. Rosko:

So, I’m going to start by how the best way that I can frame out when we talk about newly diagnosed versus patients when they have relapse. So, there are therapies that are available for patients that are FDA-approved when they are newly diagnosed with the cancer, and there are therapies that are approved only when a cancer has acted up again or relapsed. 

So, I’ll kind of frame it from patients who are newly diagnosed. And then, I also will talk more about relapsed therapies and what we’re able to offer to patients. So, in first, when we talk about treatment options, we frame treatment based on a couple things. So, one is, we talk extensively about the disease biology. So, that plays an important role in how we decide which treatment the patient should get. 

And then, the second part about how – I would probably say there’s about four main parts. And so, disease biology is one, and another thing has to do with the patient characteristics. In terms of the patient’s overall health prior to developing cancer, and also how the cancer has impacted their health in terms of everyday activities. Whether or not a person has really slowed down quickly, whether they’ve been in the hospital, and how it’s impacting their organs. Because that plays a role in terms of what we’re able to give patients.  

If a patient has advanced kidney failure, which can sometimes happen, or if you have to focus more on protecting their bones and if there’s concern about fractures and things like that. And then independent of patient characteristics in terms of overall health, the last part I talk to patients about is their own preferences. It’s a hard thing to talk about, shared decision-making in a cancer that most people have never heard about, but there is certainly – when we talk about options and there are, it’s important to talk about shared decision-making in terms of what’s most important to them and where they – and most patients will say, “Well, I just want the best medicine.”  

And I say to them, “Well, you know, we have lots of options, and that’s the best thing about it, but we also want to be cognizant of the real world, of giving best options,” and for example, Many of my patients – so, I’m at The Ohio State University, I’m here. And a lot of patients travel. I have a lot of older patients that I care for, and they’re very independent with travel. And I want to make sure that whatever therapies we’re getting for them, that we can do this in such a way that maintains their lifestyle.  

So, the beginning part of a treatment, it is broadly described as – when we talk about someone who was diagnosed with this, it’s this thing called induction. So, induction is when we give anywhere from two to four medications to be able to control their cancer and put it into remission. And we know that the cancer is in remission because, like we started out the conversation with Dr. Cottini, myeloma makes proteins. Oftentimes, it makes proteins, those proteins are not nutrition proteins but are cancer proteins that we can track in the blood. 

So, we can check them every month and to make sure that the patients are having a really good response, and as such, we’re able to define that they’re responding to their treatment. Because they have a beginning stage in induction, which they’re given treatment, and then the goal is to put patients put in remission.  

Depending on the overall health of the patient, a standard of care for most patients diagnosed with multiple myeloma is to undergo an autologous stem cell transplant. An autologous stem cell transplant is not a transplant in which you’re getting cells from your brother or sister and they’re being donated to you. They are your own stem cells. We get them out of you when your bone marrow is free of disease, and then we would admit you to the hospital for a more intensive therapy and give them back. 

That is often the standard of care for patients newly diagnosed with multiple myeloma, and it is recommended for most patients. Some patients get – I like to think of it as a stem cell transplant not at the time of their initial diagnosis, but later on at the time of relapse, or some patients are not candidates for a transplant or elect not to have a transplant. And all of these options are very personalized to the patient. It’s very hard to say that this is exactly what we do. 

Because it’s a strategy where it requires a lot of shared decision-making to make sure that we’re getting good disease control, good quality of life, and deep, deep remissions for our patients. So, then, if a patient gets a transplant, there’s a period of recovery, and then patients go on a pill most often, a maintenance pill that they stay on for indefinitely. 

Myeloma is also a cancer which has perpetual therapy. Very different than many other cancers, where there’s a beginning and an end, myeloma for the most part is perpetual therapy, where you get some form of therapy at higher dosages versus lower dosages over a period of time.   

So, I’m going to talk broadly about the classes of drugs that we have and how we use them to be able to define therapy. 

So, the first class of drugs are called proteasome inhibitors. Just like many other cancers, we use different types of drugs to be able to target different aspects of a cancer cell’s growth cycle.  

So, very similar to how we do other drugs, these are very specific to the cancer cell, and they’re very targeted. So, unlike some of our other kind of classic chemotherapies, many of these medicines that I’m going to talk about are very targeted at the cancer cells without causing too many other problems. 

So, proteasome inhibitors include drugs like bortezomib (Velcade), which is given as a shot, carfilzomib (Kyprolis), which is given as an IV, or ixazomib (Ninlaro), which is given as a pill. They have different indications, but they’re the same class of drugs.  

The next class of drugs is called immunomodulatory drugs, or iMiDs. This includes things like lenalidomide (Revlimid), pomalidomide (Pomalyst). Those are the most common, and then we sometimes use the drug that the original iMiD drug, which is called thalidomide (Contergan). 

These are all pills that patients take, and so that’s oftentimes very nice for patients to be able to provide therapy at home, very well-tolerated. The next class of drugs are called monoclonal antibodies. On a cancerous cell, there is a marker. 

And so, we use monoclonal antibodies to be able to target the marker on the cancer cell. What that means is very specific. To that cancer cell, so, the most common target is the CD38, that’s a marker on one of the cancer cells. And we use a drug called daratumumab (Darzalex), that can be given as an IV or a subcutaneous agent, or another drug called isatuximab (Sarclisa). We also have other markers on the plasma cell. There’s a marker called SLAMF7, which we have other drugs called elotuzumab (Empliciti), which is often used for patients more in the relapse setting. 

Understanding Relapse in Myeloma

/in , , , , , /by

Understanding Relapse in Myeloma  from Patient Empowerment Network on Vimeo.

What are indicators that a myeloma patient has relapsed? Dr. Mark Schroeder explains how relapsed and refractory myeloma are monitored and treated. 

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:

Expert Perspective Advances in Treating Relapsed and Refractory Myeloma

 Expert Perspective Why Myeloma Patients Should Weigh in on Their Care Decisions

Transcript:

Katherine Banwell:

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:

I think you’ve already answered this, but I’m going to ask you in case you give different or more information. 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. 

Expert Perspective: Advances in Treating Relapsed and Refractory Myeloma

/in , , , , , /by

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

 

Related Resources:

How Does Disease Staging Affect Myeloma Treatment Choices?

 Expert Perspective Why Myeloma Patients Should Weigh in on Their Care Decisions

 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.  

What Are Relapsed and Refractory Myeloma?

/in , , , , , , , /by

What Are Relapsed and Refractory Myeloma? from Patient Empowerment Network on Vimeo.

Dr. Joshua Richter, a myeloma specialist, explains what it means to have relapsed myeloma or refractory myeloma.

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

See More from Thrive Myeloma

Related Programs:

How to Thrive and Set Myeloma Treatment Goals

How to Thrive and Set Myeloma Treatment Goals

 Key Factors That Guide Myeloma Treatment Decisions

Key Factors That Guide Myeloma Treatment Decisions

 What Are Common Myeloma Treatment Side Effects?

What Are Common Myeloma Treatment Side Effects?

Transcript:

Katherine:

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 got to 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.  

Relapsed and Refractory Myeloma Defined

/in , , , , , /by

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

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

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

Related Resources:

Expert Advice for Newly Diagnosed Myeloma Patients

 The Role of a Myeloma Specialist on Your Care Team

 Myeloma Induction and Consolidation Therapy Defined

Transcript:

Katherine:  

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

Dr. Patel:     

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

Katherine:

How is that different from refractory myeloma?

Dr. Patel:

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

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

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

Katherine:

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

Dr. Patel:

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

Katherine:

All of those. Okay, all right.