Tag Archive for: immunomodulatory drugs

Myeloma Combination Therapy | What Patients Should Know

Myeloma Combination Therapy | What Patients Should Know from Patient Empowerment Network on Vimeo.

Expert Dr. Jeffrey Matous shares an overview of myeloma treatment classes, why combination therapy can be effective, and the importance of clinical trials in patient care and moving research forward.

Dr. Jeffrey Matous is a myeloma specialist at the Colorado Blood Cancer Institute and the assistant chair in myeloma research for Sarah Cannon Research Institute. Learn more about Dr. Matous.

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There are several treatment classes for myeloma, such as immunomodulatory therapy and proteasome inhibitors, for example, and they’re often used together. So, what is a combination therapy and why is it used so frequently for myeloma?  

Dr. Jeffrey Matous:

Absolutely, so with learned over the years in myeloma that combining different types of drugs that work in different ways, we call those classes, so different classes of drugs, combining them together is the optimal treatment for myeloma.  

And back in the day, we used to use two drugs. Then, we learned that three drugs are better than two drugs, and now, we have data that four drugs are better than three drugs. And so, we bring in drugs from all kinds of different categories for our patients. And we even know that for the non-transplant-eligible patients, for the older patients, for example, that combining drugs from different classes is really, really important to get the best outcomes. And in general, the three classes that we use – the four classes that we use when we’re treating myeloma patients initially include the immunomodulatory drugs, and examples of those are lenalidomide, also called Revlimid. pomalidomide, also called Pomalyst. Thalidomide’s (Thalomid) an older drug, but we still occasionally use it.  

And then, we have the proteasome inhibitors. Examples of those are bortezomib (Velcade), carfilzomib (Kyprolis), and to a much lesser extent, there’s one called ixazomib (Ninlaro). And these days, we know that CD38 antibodies are really important and really getting their foothold into the initial treatment of myeloma.  

Examples of CD38 antibodies are daratumumab (Darzalex) or isatuximab. And then, usually, we combine these treatments with steroid medicines to sort of increase the effectiveness of the regimens. That’s how – those are the classes that we use when we’re treating myeloma. 


Okay and have you learned about adding one treatment to another to another through clinical trials or is trial and error? 

Dr. Jeffrey Matous:

Absolutely. We would not be where we are right now without the conduct of clinical trials. I always tell my patients by the time something’s approved in myeloma, and we had things approved in 2022, the field is already moving past that in clinical trials. It’s unbelievable. So, I’ll give you an example. When daratumumab, one of these antibodies, got approved by the FDA, already when it got approved by the FDA, we knew through clinical trials that were being conducted that combining it with other types of medicines was far more potent. 

And we have countless examples of this, so yeah. Absolutely, so every treatment that we use in myeloma, we discovered and developed through a clinical trial. And I always encourage my patients strongly to consider clinical trials, and then, we have to explain, because when patients hear clinical trials, and I could be deviating a little bit here, Katherine.  

They often think about experimentation and testing things that are unproven. In myeloma, we occasionally do that, but far and away, the overwhelming majority of our clinical trials are testing agents that we know are effective. We’re just trying to figure out what the best combination is and make sure that it’s safe for patients. 

Understanding Myeloma Treatment Types

Understanding Myeloma Treatment Types  from Patient Empowerment Network on Vimeo.

What are the types of treatment available for myeloma? Myeloma expert Dr. Mark Schroeder reviews the myeloma treatment classes, including proteasome inhibitors, immunomodulatory drugs (iMids), and immunotherapy. Dr. Schroeder also discusses factors to consider when choosing therapy for patients with myeloma. 

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.

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Katherine Banwell:

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 lenalidomide (Revlimid) and pomalidomide (Pomalyst), or even thalidomide (Thalomid), 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. 

How Do Test Results Impact Myeloma Treatment Options?

How Do Test Results Impact Myeloma Treatment Options?  from Patient Empowerment Network on Vimeo.

Myeloma expert Dr. Melissa Alsina reviews the test results that are taken into consideration when choosing a treatment approach for patients.

Dr. Melissa Alsina is an associate professor of medicine in the Blood and Marrow Transplant Program at Moffitt Cancer Center in Tampa, Florida where she also serves as head of the Multiple Myeloma Transplant Program. Learn more about Dr. Alsina, here.

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We know that patients undergo testing when diagnosed. How do test results affect treatment choices? 

Dr. Alsina:

So, in general, we do a bone marrow, we check for the genetics of the myeloma cells, see what are the genes that are affected in the myeloma cells, and that helps us define myeloma as high-risk or standard-risk, and that can help us decide what treatment we want to give these patients. Unfortunately, it’s not totally well defined. 

I wish we could use that in a better way and there are drugs that could really target, but there is some information. We know, for example, that proteasome inhibitors are important for patients with high-risk myeloma, so we definitely try to include that in a patient that is high-risk, and the other thing is that patients that are high-risk, it’s even more important to get to that remission, so we’re going to push treatment to get there, treat these patients a little bit more aggressively. 

Other than that, depending on, for example, what are the blood counts – some patients have a lot of bone marrow involvement and their blood counts are very low. This is not common, but it happens, and so, when that happens, we might be more aggressive up front and give these patients more aggressive chemotherapy to clean the bone marrow before changing them to the more normal therapies because the treatments that we give, like Revlimid (lenalidomide), Velcade (bortezomib), Darzalex (daratumumab) can depress the counts, right? 

So we’re in that battle. The patients already have low counts, we give the treatment, the treatment lowers the counts further, so it’s hard to give these treatments in these settings. And then, the third thing that we take into account is kidneys. About 25 percent of the patients will have renal insufficiency when they are diagnosed. Some of these drugs, particularly the immunomodulatory drugs like the Revlimid are metabolizing the kidneys, so it’s very hard to dose these drugs when the patients have renal insufficiency. 

So sometimes, for these patients, we avoid the IMiDs up front. We give a different combination until the disease gets better, and then we introduce the IMiDs. We think these immunomodulatory drugs like Revlimid are super important in the treatment of myeloma, so we want to give them, but sometimes we have to delay starting them until the patient’s kidney function improves.  

What To Expect When Starting MPN Inhibitor Therapy

What To Expect When Starting MPN Inhibitor Therapy from Patient Empowerment Network on Vimeo.

Changing a treatment approach for your essential thrombocythemia (ET), polycythemia vera (PV), or myelofibrosis (MF) can be intimidating. Dr. John Mascarenhas, a myeloproliferative neoplasm (MPN) specialist, shares tips and advice for beginning a new therapy.

Dr. John Mascarenhas is Associate Professor of Medicine at the Icahn School of Medicine at Mount Sinai (ISMMS) and the Director of the Adult Leukemia Program and Leader of Clinical Investigation within the Myeloproliferative Disorders Program at Mount Sinai. Learn more about Dr. Mascarenhas, here.

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Katherine Banwell:

And we have another question from Craig that we received earlier. “I’m currently receiving regular phlebotomies for PV, but my doctor is considering switching me to inhibitor therapy. What can I expect, and are there side effects that I should be concerned about?”

Dr. Mascarenhas:       

So, for some patients, therapeutic phlebotomy is all that they need, and they do very well with it, and they don’t need to take a therapeutic like a JAK inhibitor or hydroxyurea, which is a non-specific treatment.

But some patients do. So, some patients where if their risk score is higher and their risk for thrombosis, that may be an appropriate indication. And some patients have a lot of symptoms with their PV. So, not all PV patients present and behave the same way. Some patients have a very low symptom burden. Some patients have a very significant symptom burden. Itching, for example can be a very annoying and very troublesome symptom for patients with PV.

And, if you don’t have PV or you don’t know someone with PV, you may not understand or realize the negative impact of having intractable itching, often associated with taking a shower or warm water.

And, that can really detract from quality-of-life and cause a lot of anxiety. So, that’s an example of where sometimes a JAK inhibitor like ruxolitinib can be really lifesaving in terms of restoring quality-of-life and functionality to a patient.

Usually, drugs like ruxolitinib are very well-tolerated too, which we’re fortunate about. There’s not a lot of toxicity associated with them. So, for example, nausea, vomiting, diarrhea, hair falling out with chemotherapeutics, you really don’t see with ruxolitinib or Jakafi. Easy bruising, headaches and some dizziness up front sometimes may be seen. They’re usually low-grade and they’re usually fleeting. And usually, the benefit, the feel-good aspect of it outweighs toxicity that can be seen with the drugs. They are immunomodulatory drugs. So, ruxolitinib or Jakafi may increase, to some small extent, but likely, real extent, infectious complications like shingles, urinary tract infections, upper respiratory infections. So, sometimes there is this increased risk. It’s often outweighed by the benefit of the drug.

But there are risks that are associated, and of course the results are not guaranteed. So, I always warn patients, be careful when you look at the package inserts or talk to the physicians. Risks are risks. They’re not guaranteed. So, most patients don’t have these toxicities, but one is at risk for toxicity whenever they take any medication.