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First-Line Treatment Options & Side Effects

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Published on March 15, 2021

What Are the First-Line Treatment Options for Multiple Myeloma?

What are the first-line treatment options for a newly diagnosed multiple myeloma patient? What questions should you ask your doctor to determine the best course of care for your needs? Finally, what are some of the side effects patients may face?

In this video excerpt from our recent "Dinner with the Docs" program on living with multiple myeloma, host and patient advocate Jack Aiello is joined by Dr. James Berenson, MD, Founder and Principal of the Berenson Cancer Center and Dr. Alberto Bessudo, MD, FACP, Medical Oncologist at the Compassionate Oncology Medical Group to discuss everything you need to know about first-line treatments.

Support for this series has been provided by Karyopharm Therapeutics. Patient Power maintains complete editorial control and is solely responsible for program content.

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Transcript | First-Line Treatment Options & Side Effects

Jack Aiello: Welcome to Dinner with the Docs for Southern California, featuring our local multiple myeloma experts. My name is Jack Aiello. I'm hosting the event tonight. Here with us today are Drs. James Berenson in West Hollywood from the Berenson Cancer Center and Dr. Alberto Bessudo in Encinitas from the California Associates for Research and Excellence. Dr. Berenson, would you please introduce yourself?

Dr. Berenson: Yeah. Hi, I'm Dr. Jim Berenson and I have several hats I wear. One is I’m the Medical and Scientific Director at the Institute for Myeloma and Bone Cancer Research in West Hollywood, California. We do preclinical treatment of myeloma. We try to develop new therapies, new ways to monitor myeloma, all before it gets into the clinic. And then we have a practice group. We see about 150 patients a week with myeloma, and we do all of their treatment right here in West Hollywood.

Jack Aiello: Thank you, and Dr. Bessudo?

Dr. Bessudo: I'm a medical oncologist practicing in a very large community practice. I was at UCSD for maybe 12 years doing immunoglobulin and myeloma, lymphoma, basic research. And then in the year 2000, came out of private practice. I do a lot of lymphoma and myeloma as part of my specialty in this large community medical group.

Jack Aiello: Thank you very much. So, I want to open up our very first poll, and that is to find out how long you've been living with multiple myeloma. So, most of the folks are between one and five years. Less than one year are quite a number, 23%, more than 10. And one person diagnosed with MGUS or smoldering.

For my own story, I live in San Jose, California. I was diagnosed with stage three myeloma 26 years ago. It was much easier to make treatment decisions back then because we only had two treatment options, melphalan and prednisone oral therapy or transplants. And since I was young, I had a tandem transplant, which actually didn't last that long for me. So, I had other treatments like the original thalidomide (Thalomid) clinical trial and some other chemo, none of which really worked well until I finally had one last option available to me in 1998. And that was a third transplant, except this time referred to as an allogeneic transplant. So, I had a donor give me stem cells and that worked well. Today the good news is that myeloma patients have so many more treatment options. So, Dr. Bessudo, if you have a well diagnosed, newly diagnosed, myeloma patient, do you have a standard first treatment that you like to use or are there still more questions that you ask about that patient?

What Are the First-Line Treatment Options for Newly Diagnosed Myeloma Patients?

Dr. Bessudo: Well, I don't have a treatment that I will use all the time. It really depends a lot on the situation. But of course, as a first line, I like to use a proteasome inhibitor that will be drugs like Velcade (bortezomib) or Kyprolis (carfilzomib). Velcade is a drug that I'm going to use number one. Of course, in the immune modulators, I like to use Revlimid (lenalidomide), and I used to use dexamethasone (Decadron). Clearly the combination of the drugs [inaudible] will get into remission or a good response, most patients. There is also the regimen that Dr. Berenson has published, I'm sure he's going to talk about it, when you use a very small dose of Doxil (doxorubicin), which is very simple to administer without toxicity. You can combine that with Velcade, a proteasome inhibitor or dexamethasone. I always use dexamethasone. Dexamethasone is the glue to all these treatments.

But sometimes I have patients that come in with a neurologic deficit. And as an example, I just met last Thursday, a patient came to me with Parkinson's disease. Parkinson's, he has neurologic problems. He can barely walk. He talks very slow. I was not going to do Velcade on this patient, right, I was not going to risk any bit for him to develop neuropathy, which is numbness due to the drug. So, on that patient, I'm actually going to treat him with Doxil and dexamethasone, and I'm going to have Revlimid in there just because I did not want to start with Velcade. Usually, it is going to be these drugs that you want to get started.

Jack Aiello: Dr. Bessudo, following that induction treatment, do you then put them on some type of maintenance, or do you just keep them on that first-line treatment until their numbers progress?

Dr. Bessudo: No, I wait for them to get to a stable place where the myeloma proteins is not going down anymore, or their overall renal function stops improving, or the level of red cells stops improving. Once they have been maybe three months in a stable way, I do move on into a maintenance regimen. And that varies, what is going to be that regimen. The most common one that I would use is to give them a lower dose of Revlimid, and I give them only once a week, dexamethasone, which is a very common regimen.

I have to say that I have many patients with Dr. Berenson that live in the San Diego area, and they stay on a [inaudible] regimen, that actually I'm finding to be fantastic and better tolerated than the dexamethasone. I'm learning from Dr. Berenson. When they go into maintenance, rarely I do a Velcade. That is with less frequency. Instead of doing once a week, we would want to do the Velcade every three weeks. My favorite place to stay, would be Revlimid maintenance treatment, and I always do that.

Jack Aiello: Dr. Berenson, is that the same for you? Do you typically move to Revlimid, or is something different?

Dr. Berenson: Well, I tend to continue the drugs the patient’s on, with the exception of the chemotherapy. So, the patient treated with say Doxil, Velcade, and dex, we drop the Doxil at the time that their protein level levels up, usually after five to eight months. Then we continue the Velcade every other week and we maintain steroids. We do, however, give a slightly higher dose of Velcade, cause we're only giving it twice a month. Then I use Revlimid as a maintenance, if the patient is getting Revlimid upfront. However, there's a good oral option now for Velcade, as some of you know, Ninlaro (ixazomib). We're currently conducting a clinical trial among patients who do get Velcade and Revlimid. Again, they have to have Revlimid and Velcade, and seeing if the Ninlaro alone, which looks pretty good with some recent data, is just as good as Ninlaro with Revlimid.

There are a lot of patients now on Ninlaro maintenance, on Revlimid maintenance, on the combination. I don't stop treatment except if the patient's tolerability is poor. For example, the patient who was in today was on that study, and he did not tolerate the Ninlaro and he's not having so much fun with Revlimid. We may just stop. I saw a lady yesterday like that. She stopped three years ago because of the GI side effects, that stomach and the diarrhea, with the lenalidomide or Revlimid, she's still in remission. So, the more we see, the more we learn, not everybody's the same.

Jack Aiello: Yeah. We've gotten questions already about side effects, such as nausea and neuropathy. Can you talk about that kind of stuff, side effects that you see from first-line treatments?

What Are the Side Effects of Multiple Myeloma Treatment?

Dr. Berenson: Yeah. I mean, I'm a big believer that people have to maintain their quality of life. So, I've used lower doses. I don't use Velcade at the standard dose. I use 30% less, because in the first trial we ran 20 years ago, it worked just as well. Similarly, the doses of Revlimid I use are about a third of the FDA approved dose. The same with Pomalyst (pomalidomide). We're seeing the same thing with the new kid on the block, selinexor (Xpovio). Very active at much lower doses than the original trials. So, the FDA may approve trials at a given dose, it doesn't mean that you have to get that dose. When you get those higher doses, you get toxicity. Maybe neuropathy with Velcade, that also can be mitigated, we believe, with using over the counter supplements like alpha-lipoic acid, which I think really helps reduce the amount and the severity of neuropathy.

We also know, for example, Ninlaro, the oral Velcade, causes less neuropathy than Velcade. In terms of nausea, not as much a problem with the frontline. It can be with some of the later line treatments. Certainly, diarrhea can be a long-term problem, as we know with Revlimid. It's totally related to dose and it's very responsive to bile acid binders, like Welchol (colesevelam), cholestyramine, and Prevalite powder. These things work quite well. I think it's really important to talk to the patient, to find out what side effects they are having, what may be the co-conspirators that are causing it beyond the myeloma drugs. Because there may be totally unrelated things going on that may be causing it.

For example, a patient is in a beautiful remission - the sickest patient I ever saw, and she's in complete remission, four months, five months later. Terrible stomach pains, saw the GI doctor told her it must be in her stomach, must be ulcers. Then I sent her to my guy, and he said, no, she's got abdominal muscle pain, she just needs a nerve block. A lot of these things need, really, specialists. And don't also think that you know everything, if you're not sure maybe you should go ask the doc, maybe I need to see the GI guy. Maybe I need to see the kidney, the orthopedist. The oncologists are oncologists, they don't know everything.

Jack Aiello: Yeah, that's really good advice. I'm always telling patients to get experts like you on your medical team, even as a consultant and such. But to even get the nephrologist, or the doctor who specializes in nerves and such, get them to be part of your medical team, because not everyone knows everything. Dr. Bessudo, side effects, anything to add in terms of—Dr. Berenson said that he will typically lower doses, sometimes substitute treatment.

Dr. Bessudo: I agree, that if you start with the doses that have been approved and recorded by the FDA, you really get more into trouble with toxicity. I try to explain to my patients that the way drugs get approved is by these pharma companies find the higher dose, the highest dose possible, and then they choose the drug as the drug they will put on a clinical trial. If the clinical trial is successful, that is the dose that comes and has to be used by the doctors. But it never has to be that high. So definitely, that's the case with Revlimid, for example. I never use 25 milligrams, even as low as 10 milligrams is going to work, trying to prevent toxicity.

The one that I worry about the most is the neuropathy. Some people with myeloma already have some neuropathy, due to the disease. So that's the one that I am more careful with, and more and more, I find myself not trying Velcade in the first line. I'm using a little bit of the dara -monoclonal antibody, even in the first line of patients that I think that the neuropathy is going to cause trouble. When you say proactive, you need to start the drug at the dose that you think is going to work. And you see the patients very frequently so that when they have a side effect, you do the tuning off of the dosing. And of course, quality of life is always the most important thing, you have to prevent side effects.

Jack Aiello:  Dr. Bessudo, Dr. Berenson, I want to thank you both. And remember, knowledge can be the best medicine of all.


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