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Beth Is Diagnosed With Triple-Class Refractory Multiple Myeloma


Dr. Elie Fahed explains Beth’s diagnosis of triple-class refractory multiple myeloma and targeted therapy, and Beth recalls symptoms and side effects she experienced.

Elie Fahed, MD: Beth, let’s go back to you. The honeymoon didn’t last too long: 2 or 3 years, and we started having lesions and pain again.

Elizabeth Ayen: Right.

Elie Fahed, MD: You said it was your ankle, so you had to be in a boot. We did some radiation.

Elizabeth Ayen: Right.

Elie Fahed, MD: We tried a different regimen. We tried carfilzomib, elotuzumab, formulas from lithium chloride, and more recently, around August or September of 2020, we diagnosed you with what we call triple-class refractory disease. Let me explain what that means. In 2021, the mainstay of therapy for multiple myelomas is IMiDs [immunomodulatory drugs], with medications known as lenalidomide and pomalidomide. We have proteasome inhibitors, like Velcade [bortezomib] and carfilzomib, and then we have anti-CD38 antibodies, mainly daratumumab. Those are what we call triple-class agents. Those are the main classes we use for treatment with multiple myeloma.

Sooner or later, at some point, the disease will become refractory to those 3 classes of medication, and we call that triple-class refractory disease. It is a more difficult disease to treat because we used our best weapons, and we are now left using what’s available. Thankfully, we have new therapies coming along. Remember those discussions we were having at that time when you were having the lesion in your sternum progressing, and you were having more and more lesions? What was going through your mind? Were you concerned? Were you worried?

Elizabeth Ayen: Yes. My light chains were going up so much too, and they were up to 70 at a certain point, and my tumor was very large where you could see it just by looking at my chest. It was concerning to me. I was feeling terrible. They were having to push me around in a wheelchair. Right around that time was when I had to be in the hospital for three months in a row for pneumonia, and I was not doing well at all. I was concerned because I thought, “What do we have left on the list?” I wasn’t sure that there was anything that was going to help at that point. I do not know if this is the right time to bring this up, but we started Empliciti [elotuzumab] as well, and that did basically nothing for me.

Elie Fahed, MD: Over the years, your story is that you were at the right time when there were new approvals. Whenever a new medication was approved, you were ready to get it and get the benefit from it.

Elizabeth Ayen: Yes.

Elie Fahed, MD: At that time, I discussed doing BCMA [B-cell maturation antigen]-targeted therapy with you, which is a new way of treating multiple myeloma. BCMA is a protein we find on all myeloma cells, and it can be targeted in different ways. We have direct monoclonal antibodies, what we call ADCs [antibody-drug conjugates], like Blenrep [belantamab mafodotin], which we used. Or we can target it with what we call CAR [chimeric antigen receptor]-T cell therapy, where we take your own cells, train them to attack BCMA, and give them back to you through infusion. We had that discussion, and you expressed that you were not interested in going to a big center in a big city to get CAR-T therapy, which is still experimental and not yet approved in multiple myeloma as of today.

We had approval for Blenrep as a medication, and we decided to go that route. As I said, Blenrep is an antibody-drug conjugate. It’s an antibody targeting BCMA, connected to a toxin called MMAF [monomethyl auristatin F]. It’s a microtubule inhibitor. Whenever that antibody connects to myeloma cells, to the BCMA, it gets internalized, and it causes apoptosis, or death of the myeloma cells. It comes with one significant and serious toxicity. 

Elizabeth Ayen: Yes. 

Elie Fahed, MD: The toxin attached to the antibody can cause a serious keratopathy. It can technically attack the outer lining of the eye, causing painful dry eyes and decreased visual acuity. Those drugs can only be given via a REMS [Risk Evaluation and Mitigation Strategy] program. You went through this, so maybe you can tell us about it. You needed an eye examination before each infusion.

Elizabeth Ayen: Right.

Elie Fahed, MD: Tell us about that experience.

Elizabeth Ayen: I would have to go a week before each infusion and have my eyes tested, and then the eye doctor worked with Dr. Fahed to decide whether I could do the next treatment, depending on how bad the inflammation in my corneas was. There were a couple of times where we had to skip treatment because it felt like I had rocks in my eyes. I was having double vision, and it seemed, I don’t know if it was caused by this, but it seemed that the cataracts were getting worse. I was very foggy, and so it depended on how bad it was and what level the eye doctor would set where I was. Dr. Fahed would then have to decide whether I could have the next treatment, so it was pretty awful because I couldn’t drive. I still can’t drive because of the cataracts right now, but I couldn’t drive. I could hardly see anything, so it was not a fun thing. We were hopeful that it was going to work for us to take care of the myeloma, but it didn’t do a very good job.

Elie Fahed, MD: You were unlucky. We do not get lucky every time, but it’s a helpful medication, and it can help quite a bit. About one-third of patients will have a good response to it.

Elizabeth Ayen: Yes.

Elie Fahed, MD: The problem is that we have to be careful about the eye toxicity. It can decrease visual acuity for some patients. Like you said, you couldn’t drive, and you had some discomfort. Before each visit, we need to have the eye exam done by an eye specialist, and depending on the numbers they see on their exam, we can decide if we need to treat you or delay therapy. I remember we had to delay it once or twice in your case, and we had to lower the dose because of toxicity. That is an expected side effect. We discussed it ahead of time.

This transcript was edited for clarity.

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