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Managing the Side Effects of Myeloma Treatment

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Published on July 10, 2020

Dr. Rafael Fonseca from the Mayo Clinic Arizona discusses strategies for managing toxicity and side effects from myeloma treatment with Patient Power co-founder, Andrew Schorr. "We're learning how to use drugs better" explains Dr. Fonseca. They discuss how adjusting dosage and adding supportive care an preventative medications can be useful techniques to treating side effects and toxicity of certain myeloma medications. Dr. Fonseca reassures patients,"We have many ways to manage myeloma and manage toxicity and side effects as well."

This program is sponsored by Karyopharm Therapeutics. This organization has no editorial control, and Patient Power is solely responsible for program content.

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Transcript | Managing the Side Effects of Myeloma Treatment

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Andrew Schorr:

Hello, and welcome to Patient Power. I'm Andrew Schorr in Southern California. Joining me from the Mayo Clinic in Scottsdale, Arizona is a world-famous myeloma specialist and that's Dr. Rafael Fonseca. Dr. Fonseca, welcome back to Patient Power.

Dr. Fonseca:

Oh, thank you. It's my pleasure to be back here with you.

Andrew Schorr:

 So Dr. Fonseca, there are some people where myeloma is more advanced. Maybe they've been through many lines of treatment. But we have more medicines now than we've ever had before. Talk to us about what are the options now for people with more advanced myeloma, and these are powerful drugs, they can have side effects, how you manage that.

Dr. Fonseca:

Sure. Well, thank you. We're in the very fortunate situation that we have more and more drugs available for the treatment of myeloma. I'm sure the audience knows about their names and their passage through the FDA approval process. So drugs that are really now mainstay in the treatment of myeloma that comes back, so relapsed myeloma, include of course, daratumumab (Darzalex)-based combinations. We have the use of carfilzomib (Kyprolis) also, which is often used in combination. Among the IMiDs, so the class of drugs that belongs to the thalidomide (Thalomid) and the lenalidomide (Revlimid) of the world, we use quite a bit of pomalidomide (Pomalyst). Now, our horizons have expanded beyond that because we have the availability of new drugs such as selinexor (Xpovio), and we can talk about that. Recently, the BOSTON trial was reported, which was a favorable trial. We also have the advent of oral drugs, which, in this present time, really provide us with additional tools in how we think for the long term management.

Now, more than ever, it is critically important that people pay attention to toxicities, because myeloma patients now can live for many years after a diagnosis. So carrying the burden of a toxicity, particularly one that you're going to carry for longer, it's really not something we want to see. So we have to be extra careful and attentive to prevent some of those toxicities that might be there for the long term for patients.

Andrew Schorr:

Let's talk about selinexor was a whole new class of medicines being added often for people who are running out of options. It's a powerful drug, and I knew some people were maybe hesitant about it because they said, well, there's serious side effects, but I know you, with your range of supportive care, you have things that can help people still fight the myeloma, but treat the side effects as well. Maybe you could talk about that.

Dr. Fonseca:

Absolutely. It's very clear that when it was first approved, it would be fair to say that it was off to a rocky start, primarily because of some of the toxicities that we're seeing in the dosing and schedule as it had been originally approved, but as it's true for many of our myeloma drugs is we've learned to use them better. We have found more ways to give them in a way that it's acceptable for patients and they feel like their toxicities can be managed. In particular, the big one with selinexor has been the effect of the loss of appetite, the nausea, and some of the weight loss. Some of the changes that have been done now is to administer it once per week.

Now, many in the audience would remember that was the story of bortezomib (Velcade). That was a story of carfilzomib, often now used once a week. When we started with thalidomide, we used 800 milligrams, nowadays we wouldn't do that. Dexamethasone (Decadron), we went from giving 12 days, every 28 days at 40 milligrams, and that's why we sometimes see the term now lower dose of dexamethasone. I think selinexor is no exception to this. So we're finding out that, A, weekly administration is much better tolerated, but, B, and this is critically important, people have to provide the preventive medications to help with the nausea. Usually now, from what we know, you have to use at least two medications for nausea, usually there's the use of dexamethasone as well that helps with that. So hopefully, if a patient can do that and stay on treatment, then we might see the effects that we're seeing with response. 

I'm actually quite hopeful about the changes. As I mentioned, the BOSTON trial was very clear for the effect of selinexor. In fact, just recently, just a few days back, it was approved as well too, for the treatment of relapsing lymphoma. So a lot of this is just learning those nuances of those details of how to best use those medications.

Andrew Schorr:

That's what happens, as you said, over time. So you have more drugs for more versions of myeloma, as people are on a long journey. You and your career have seen just tremendous advances, and you continue to look for how dosages can be changed in effective combinations. You referred to this BOSTON trial, which came out at the American Society of Clinical Oncology using selinexor in combination with other drugs. So the whole, which combination for which patient when, what supportive care when, but it still gives people a great deal of hope where few years ago we didn't have that.

Dr. Fonseca:

Oh, absolutely. There should always be room for hope. There is one concept I frequently weave into the conversation when I talk about a myeloma and the new treatments, particularly as they show this slide for current stats for survival. If you have a myeloma patient who were to be diagnosed now, and let's say that person is eligible for STEM cell transplant, there's a good likelihood that that person will be able to live 10 years plus from that moment of diagnosis. Now, I know that's not perfect. The perfect solution would be one pill, it's over. You don't have to deal with that again, but that's a substantial change from where we were before. The point I was going to make, that has two elements of value.

The first one is that you have the disease controlled for that period of time. So it's much better than we ever had, but the second one, and it's important to recognize this, is during those 10 years, we have 10 years of clinical research and new developments. So if I were to see someone today in 2020, I would have to tell them, with my tools of 2020, this is what I can achieve. How am I going to be treating multiple myeloma in 2030? Boy, is that an open question?

Andrew Schorr:

Right. There's been a tremendous evolution in myeloma. The addition of selinexor, new combinations, even new dosing. For instance, now you have a faster dose of daratumumab.

Dr. Fonseca:

It's just incredible and daratumumab has precision through the subcutaneous formulation, so it's a new option for patients. I haven't even mentioned what we're seeing with immunotherapy approaches. There's two big lines of work there in myeloma. One of them is the T-cell engagement, be that through the process of CAR T-cells or through the use of bispecific antibodies, number of clinical trials showing significant benefits. So that's hopefully in the near future as an extra option through approved medication for our patients, but as we get there, there's just a plethora of clinical trials in that regard.

On the other side, I said there were two tracks. The other track are the conjugated antibodies, and the prototype for this is belantamab. So belantamab, as a single agent, has a very high level of activity against multiple myeloma. All the clinical trials that have been presented in that regard show that it will be a tool that will be added to our kit for the treatment of this disease. It does come with its own set of toxicities, in particular issues related to some ocular toxicity, in the form of keratitis. But again, there, my hope is that as we get going and we know how to use it, perhaps through some preventive strategies or some remedies that will help alleviate that, then it would be right there in the mixture of what we're doing for the treatment of myeloma patients.

Andrew Schorr:

Wow. So just to sum up more approved options, others in research like you were just mentioning, so this is an ongoing discussion for someone. As you said, what you can offer this year is different from last year and what you'll be able to do in the years to come are going to change as well. So while you dream for cure, but short of a cure, you have many ways to manage myeloma and reduce the toxicity of the drugs as well.

Dr. Fonseca:

Absolutely. It's fair to say to, as we dream of that and as we're learning how to better and more safely use these drugs, they're all moving up front. It's like you go from the minor leagues, if you may, to the major leagues, and whether we're seeing with the upfront treatment is just a continuing increase in the number of patients who get very deep responses. We don't think the classic methods are even sufficient anymore. So we go through the MRD determination and regimens that are now including four drugs with the idea still with a transplant, that who knows in the future may end up being dispensable. I still like it. I think it's an important tool, but just taking those patients to very deep responses, achieving MRD negativity appears to be a very important goal with the first line. We're even achieving that now with second line therapy for multiple myeloma as well.

Andrew Schorr:

Wow. Well, I think for our listeners and viewers, it's really important to have a discussion with a myeloma specialist, such as Dr. Fonseca, and really see where you are in your journey, and don't give up, because options continue, both newly approved options and management of that, dosage changes, side effect management, and of course, always clinical trials. Dr. Rafael Fonseca from the Mayo Clinic in Scottsdale, Arizona, thank you so much for being with us on Patient Power.

Dr. Fonseca:

Thank you for the opportunity.

Andrew Schorr:

I'm Andrew Schorr. Remember, knowledge can be the best medicine of all.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

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