What types of BCMA directed therapies are being explored in myeloma?

What types of BCMA-directed therapies are being explored in myeloma? In cancer in general, when you would like to target the cancer cell, you have to identify what we call a tumor antigen, which is a marker that you can find at the surface of the malignant cell. When it comes to multiple myeloma, there are several tumor antigens. One very popular tumor antigen and target these days is the so-called BCMA, and it stands for B-cell maturation antigen. In another word, it is a molecule on the surface of the plasma cell, the malignant, the nasty malignant plasma cell that is present in almost 100% of cases, and that makes it a very attractive target to try to kill this malignant plasma cell. And this is where we are fortunate today to have different agents that can target BCMA. And these agents rely on different technologies. Today, when it comes to drugs being approved, we have three families of drugs that then target BCMA. We have, for instance, the antibody drug conjugate, and this is about having a sort of a monoclonal antibody combined with a chemical product. This, what we call antibody drug conjugate, can come and stick to the malignant cell, and it allows the destruction of the cell. We have also what we call the bispecific antibodies, and they are also called T-cell engagers. What does that mean? These antibodies actually can target two antigens. The BCMA, this is the one you would like to reach on the tumor on the malignant cell, but they can target also another antigen we call CD3, and CD3 is a marker of the lymphocytes. So the lymphocytes are the soldiers that are capable to kill the malignant plasma cell. So with a bispecific antibody, you are giving a drug that on one hand can catch the lymphocyte, and then it can bring it to the malignant plasma cell, link it there, and then through the BCMA, you induce a killing cascade. The third family that can target BCMA is about the CAR T-cells. So here, this is about true cellular therapy. So how does it work? You take out of the blood of the patient some T-cells through a process we call aphoresis. It's not a dangerous, it's relatively comfortable process. You collect these lymphocytes. These are the soldiers that we would like to educate, to engineer. So they are outside the body. They are engineered to target BCMA, and once they are ready, they are in a bag, and again, they are infused into the body of the patient after certain preparation. I will not go through the details. And these lymphocytes that are infused into the body, actually, we have educated them to target BCMA, and again, they go immediately to the malignant cell, the one you want to get rid of, and they link to it, and the killing of the plasma cell can occur. An interesting parameter about these cells is that they can proliferate. So you can have sort of an endless number of soldiers, and this is the beauty of CAR T-cells, which are considered as a living drug, and they are bringing a lot of hope to patients with multiple myeloma. So B-cell maturation antigen, or BCMA, is a target that people really are excited about, and that's because it's expressed in essentially all myeloma cells. And it's not expressed in normal cells in general. So this target has been seized upon as something that's really special in myeloma, and there's three general ways to target BCMA that are being either available or explored. So one is using a drug-antibody conjugate, and that's this drug, Blandtumab, that was approved in 2020, and it targets BCMA and brings in a drug called R-Astatin F that helps the myeloma cell from not dividing. Now the response rate for this drug was about a third, but it is available immediately. So if somebody needs to get a therapy and they've had a very aggressive myeloma, this is an option. The FDA recommended that the marketing application for Blandtumab mafidotin for patients with previously treated relapsed or refractory multiple myeloma be withdrawn after determining that findings did not meet the requirements for accelerated approval. Glenrip is still being studied in combination therapy and clinical trials with promising results. The second is a CAR T transplant, and there is one CAR T product that's approved, which is idacaptagene or idacel. Trade name is a BCMA. And CAR T transplants are very exciting in myeloma, primarily because it's a therapy that has a really high response rate. So if you looked overall in the CARMA 1 trial, the response rate is about 75 percent, but in people who have a complete remission, it's much higher in the closer to the 80 to 90 percent range. One of the issues with a CAR T transplant, however, is there's a lag time, so that you have to have cells collected and manufactured, and you have to be stable for a while to get the treatment. And so unfortunately, some people just can't do that. Even if they're offered bridging therapy, their myeloma is so aggressive, it's very difficult. Probably coming soon is cilticell, which is another CAR T product, maybe a little bit better response rate, but those options are great for patients. Again, the response rates are wonderful, and one of the big things for people that my patients love is you get to be off therapy for a period of time, which is just great. Since the filming of this video, the FDA approved on February 28, 2022 a second CAR T product, cilticaptu gene autolusil, for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. And then the third class of drugs that is coming sooner by specific engagers, and these are drugs that basically sort of connect a T cell, an immune cell, with a myeloma cell. Now, not all of them are BCMA-directed, but the one that's probably farthest along is a drug called teclistumab, and these drugs also are off the shelf. They have response rates that are very high as well, not quite as high as CAR T, but 60 or 70 percent, and that looks very exciting, and some of these drugs are given intravenously, some subcutaneously. Since the filming of this video, two BCMA-directed by specific antibodies have been FDA approved. On October 25, 2022, the Food and Drug Administration granted accelerated approval to teclistumab, and on August 14, 2023, the FDA granted accelerated approval to elrinatumab.