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Relapsed Multiple Myeloma: Finding the Best Treatment Option


Kenneth Shain, M.D., Ph.D., and Marcella reflect on how she didn’t tolerate her second line of therapy for multiple myeloma well and moved to a novel treatment regimen thereafter.

Kenneth H. Shain, M.D., Ph.D.: In 2019, we unfortunately started seeing the myeloma numbers we monitor start to climb back up again. That was about seven or eight years after the transplant.

Marcella Worrell: Yes.

Kenneth H. Shain, M.D., Ph.D.: You were in remission for that long.

Marcella Worrell: Yes.

Kenneth H. Shain, M.D., Ph.D.: Can you walk us through how that happened? When you first started realizing things were coming back, what did that look like from your perspective?

Marcella Worrell: There wasn’t any pain like back pain or anything like that. I’d usually go to my doctor every six months. We switched it from every three months to every six months, and one day I went back, I wasn’t feeling up to par. He told me from the blood work that it looked like my myeloma was coming back. I said, “What?” I was not happy, but I knew what to expect because I had been through it before. But he said, “It’s not that high,” and I thought, “OK, good.” We did a biopsy and he confirmed that it was myeloma. But this time, I was asleep, thank you, God. That’s when I first found out, but I was in a better place as far as my son, my life, and my health. I knew I would beat this again, that this too shall pass. That’s when I first found out.

Kenneth H. Shain, M.D., Ph.D.: That’s a very different mindset because you had been through it already and have an expectation, right?

Marcella Worrell: Yes.

Kenneth H. Shain, M.D., Ph.D.: And maybe we caught it because we were watching you before those bad things happened to you. There was no high calcium, no pain, and no kidney issues. That emphasizes the importance of making sure you stay followed up so we can keep an eye on you, right?

Marcella Worrell: Yes.

Kenneth H. Shain, M.D., Ph.D.: Those are important messages you’d probably say and give out to anybody who’s listening, right?

Marcella Worrell: Yes, that’s true.

Kenneth H. Shain, M.D., Ph.D.: From a medical or clinical perspective, relapse means that we follow the M [monoclonal] spike in your serum, the M spike in your urine, the serum free light chains, and for you, your IgA [immunoglobulin A], right? Those are the proteins we’re all following that can give us a hint of how many bad guys might be growing. We’re always looking for those numbers. We don’t want them to increase, but we’re always keeping an eye out. Once they start increasing greater than 25% or over about 0.5 gram in an M spike, or we start seeing signs of organ damage—the anemia, the high calcium, the renal failure, or new lesions—those are all things we look for to see if there’s progression. When you progressed, you had a new bone marrow biopsy, new imaging, and all those laboratory tests were done again just to make sure we knew what was going on at that time, right?

Marcella Worrell: Yes.

Kenneth H. Shain, M.D., Ph.D.: How did [Daniel] Spitz, [M.D., FACP,] at that time say we are going to choose the next line of therapy? Did I help choose your next line of therapy? I know you’re the boss, so neither of us probably chose it. You chose it.

Marcella Worrell: He put me back on the Revlimid. I did that for one session, the pills, and I told him, “No, it’s not working. I’m getting those cramping pains again.” I thought it would be different. After one session of doing that, we switched to a different kind of pill, but I think it was his assistant and she gave me something too low. He switched me back to, not the Revlimid, but something else.

Kenneth H. Shain, M.D., Ph.D.: Yes, pomalidomide, or Pomalyst.

Marcella Worrell: Yes, that’s the name. After I did the first session, he said, “Maybe we should talk to Moffitt [Cancer Center] again.” They were talking about bringing me down there and potentially doing a second stem cell transplant. When I talked to [Doris] Hansen, [MD,] she said we need to first get me in a different place, so she communicated with Dr. Spitz and told him to do the drip instead. Instead of the injection in my stomach, it was the drip for my blood in my vein. We did that, and it was like night and day. Whatever he gave me, he was giving me two different medications. Every other week, I would do two, and then the third week, just one, and so on.

Kenneth H. Shain, M.D., Ph.D.: You didn’t tolerate what we started then. It’s another important story to tell, that you didn’t tolerate Revlimid. We knew that already. There’s a cousin to Revlimid called pomalidomide, which is in the same class of immunomodulatory drugs. Some people tolerate one and not the other, and vice versa. Unfortunately, the pomalidomide, at least from what I remember, caused your counts to drop too much. You became neutropenic. It was too much for your bone marrow to handle, but I thought it was tolerated a little better. So then we decided to change it up and use different mechanisms of action. We decided to use a drug called Darzalex, or daratumumab; a drug called Kyprolis, or carfilzomib; and then we always love dexamethasone because it kills bad guys really well, although we know it tortures patients a little .

Marcella Worrell: Yes.

Kenneth H. Shain, M.D., Ph.D.: We started that way. At the time, Darzalex with Dr. Spitz had to be given, and it’s IV [intravenous] over a long period of time. We transitioned to it being under the skin so it was faster later on.

Marcella Worrell: Yes.

Kenneth H. Shain, M.D., Ph.D.: Then we started that. So now we have a monoclonal antibody that targets something on the surface of myeloma cells called CD38, and that’s the daratumumab, or Darzalex, drug. That’s an IV now, it’s a subcutaneous injection given weekly for eight weeks, then every other week for eight doses, and then monthly, which is a pretty nice schedule. The Kyprolis is the other IV you had. It was given once a week, three times per month.

Marcella Worrell: Yes.

Kenneth H. Shain, M.D., Ph.D.: We spread that out later on. That’s a proteasome inhibitor, like the Velcade was at the very beginning. It’s another agent in the same class. And then there’s dexamethasone. That’s how we wanted to attack your disease, in part because you didn’t tolerate another class of drugs, the immunomodulatory drugs. That’s the reality of being a patient. You can’t help what you tolerate. We started that in 2019, and now it’s 2021, and you’re in a very good partial response with a 90% reduction in disease burden. That’s a really good way of thinking about things, right?

Marcella Worrell: Yes. I do the drip once a month now. I’m thinking you needed to change the dexamethasone or reduce it. I think it’s something different, which makes me feel a little better. I also take Tylenol and Benadryl.

Kenneth H. Shain, M.D., Ph.D.: And the antihistamine.

Marcella Worrell: I do all of that once a month.

Kenneth H. Shain, M.D., Ph.D.: Because you’re doing so well, we took the Kyprolis away, maintaining efficacy without any extra toxicity. Your Darzalex is once a month, and then because you love dexamethasone so much, we’re trying to get rid of the dexamethasone, too. So it will just be Darzalex and maybe a little of dexamethasone.

Marcella Worrell: Yes, a little, which is working really well for me.

Kenneth H. Shain, M.D., Ph.D.: How has this therapy been intertwined with your daily activities? Is it something you had to learn to go through and now it’s part of every day, or is it still difficult to manage with everything else going on?

Marcella Worrell: It’s not difficult at all. I feel much better on it. The first day [each month] after I come out of the hospital after the drip, I have the downers from the dexamethasone, but it’s not as bad as in the beginning. And with Benadryl, sometimes I don’t know if I’m asleep or awake. But I don’t go to work the first day. I just take it. The rest of the time, I feel fine. I feel better. There’s no pain in my legs or anything. I drink a lot of liquids, which helps, and I don’t have cramps as much. But I sweat a lot when I’m out there, so that’s part of my problem, too. So I drink a lot more water or different liquids.

Transcript edited for clarity.

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