Published on January 9, 2020
- The definition of BCMA, CAR-T and ADC
- As of 12/19, there is not an FDA-approved BCMA drug for myeloma
- Ask your doctor about a BCMA-directed treatment approach or clinical trial
What do BCMA, ADC and CAR T mean for multiple myeloma patients? Expert Dr. Sikander Ailawadhi explains the meaning behind the “alphabet soup” of acronyms to help patients understand important genetic markers seen in myeloma and novel, sometimes complex targeted agents discussed at the 2019 American Society of Hematology (ASH) Annual Meeting & Exposition. Watch as Dr. Ailawadhi explains how researchers are targeting the underlying genetics of myeloma to treat patients with approaches like CAR T-cell therapy, BiTES and antibody drug conjugates.
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Transcript | Myeloma Treatments: Understanding the “Alphabet Soup”
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Hi there. This is Esther Schorr. I'm here with Patient Power at ASH 2019 along with about 25,000 hematologists and oncologists and wonderful researchers. I am standing here with Dr. Sikander Ailawadhi.
From the Mayo Clinic in Florida, and, Dr. Ailawadhi, thank you for being here.
Absolutely. Thanks for having me.
It's our pleasure. So what I wanted to talk to you about is multiple myeloma. I know from the chatter at ASH that there's this kind of this alphabet soup of things going on, CAR T and something with a B and all these names that I really would love to have our audience of multiple myeloma patients and care partners understand better. So maybe you could just give us a quick overview of these new treatment possibilities.
Absolutely, the alphabet soup. Yes. So I think that's an excellent question because when this information goes out patients and caregivers are obviously desperate to find out new information, get educated, but also see where there is hope. What can they aspire to get to? What will give them that next step?
So let's talk a little bit about that alphabet soup of BCMA. I'm pretty sure our patients and caregivers will be hearing about this BCMA term a lot. So BCMA stands for B‑cell maturation antigen. What that means is that B cells, which is a white blood cell type that all of us have, and plasma cell, which is the origin of myeloma, plasma cell is the final life stage of a B lymphocyte. So the B cells eventually mature into plasma cells.
So this B‑cell lineage, if I may say, has a marker on its surface, the BCMA, and since it is a marker associated with maturing B‑cells plasma cells, which are the most mature form, have this marker on their surface almost universally.
Like a tattoo.
Like a tattoo. And in some terms it is almost like something that is jutting out of the surface, so it's a marker jutting out of the surface of the cell itself. And if patients can kind of relate to something, they have probably heard about daratumumab (Darzalex), which is an antibody or immunotherapy against CD38. CD38 is another marker, for example. Similarly, elotuzumab or Empliciti, that is against a marker called SLAMF7.
So our cells have so many of these markers jutting out of them, and if a drug can go and attach to that marker and either kill the cell directly or try to kind of recruit the body's immune system to kill that complex, that is the role of immunotherapy.
So the BCMA is present on plasma cells, hence myeloma. There are several ways of how this BCMA can be targeted. The patients I'm sure have heard about CAR T. I can say that while there are different types CAR Ts or CAR Ts targeting different targets…
…chimeric antigen receptor T cells. I know, we can't make it easy. So CAR T is chimeric antigen receptor T cells, which is T cells or immune cells that have been trained to fight against some marker. The most common CAR Ts that are being developed right now in myeloma—there are several types—are BCMA‑directed CAR T. Similarly, this BCMA can be targeted by—the patients may have heard about BiTE antibodies. There are several kinds of BiTE antibodies, but BCMA is one of the targets.
Similarly patients would have heard about something called ADC, which is antibody‑drug conjugate, idea being that we are trying to kill the myeloma cell by attacking the BCMA. We can attack it by CAR T, so recruiting the T‑cells. We can kill it by BiTEs, which is also another way of an immunotherapy recruiting the T cells. We can do that by ADC, which is delivering a payload of something that can kill the cells, but the concept would be that the drug attaches BCMA and then releases that pay load so that the cells die.
And not a lot of damage around.
Not a lot of damage around. Now, what we need to remember is that, of course, unfortunately, as the proverbial term, there's no free lunch. There are unfortunately side effects, and that is what is being defined better, and one of the great things coming out of ASH is we are learning more about the side effect profile about a lot of these drugs. So side effects of CAR-T cells, durability of response of CAR‑T cells. Side effects of ADC, durability of response, etcetera.
So what in my mind, and I can say one of my approaches when I see a patient with myeloma is BCMA is such an important target right now. Unfortunately, there is no FDA‑approved drug yet. We're hoping within the next few months there will be something on the market, one of these excellent strategies. But I think the patients should be, as I said, their own advocates, be aware of this knowledge and try to ask for a BCMA‑directed treatment approach from their doctors or seek out a clinical trial.
There is actually one ADC or antibody‑drug conjugate that is being made available under at expanded use program. It is very reasonable to reach out to the doctors and say, hey, I've hear about BCMA. I know that it's an important target in myeloma. Am I a candidate for a trial? Or can you please help me find access to a BCMA drug, because I would really want to get the benefit of that strategy of controlling myeloma.
So it's not too soon to ask about those things?
It is absolutely not too soon, even patients who may not have access to a clinical trial, as I said, at least one of the antibody‑drug conjugates is being offered as an expanded access, which is a program in which before the drug is approved by the FDA there is an arrangement that the drug in a case‑by‑case basis can be made available to the patients.