What is immunotherapy?

What is immunotherapy? Well, my definition of immunotherapy is using drugs or cell products or antibodies or whatever we have that stimulates the immune system in the patient's body or delivers to the patient's body new components or new agents that themselves enhance the power of the immune system. What does the immune system do? It is meant to recognize myeloma cells and ultimately attack the myeloma cells in the hope of suppressing it and even getting rid of it, hopefully eradicating it. So immunotherapy is a lot of different things. I think the general concept is that immunotherapy is using some aspect of the immune system to fight cancer. It goes from a drug such as an antibody and our body normally makes antibodies to recognize and to fight infections. But what we have also now is technology to make what we call monoclonal antibodies, so a whole bunch of antibodies that recognize just one protein. And in myeloma, these antibodies are already in existence. I think the best one is daratumumab that has shown very good clinical promise. Other forms of immunotherapy currently being used in myeloma are something like IMIDS, lenalidomide, thalidomide, pomalidomide. All of these drugs, by modulating and potentially augmenting the ability of our native immune system to fight the myeloma, is immunotherapy to a certain extent. I think vaccines are immunotherapy. They elicit a new immune response that allows the patients to then recognize and better kill the cancer. CAR T-cells are immunotherapy. These are T-cells that have been activated and modified. And other forms of non-gene modified T-cell therapies are immunotherapy. And also checkpoint inhibitors are immunotherapy. And anything else that in the end result leads to an enhanced immune function is considered immunotherapy. So it's a very broad general term. Immunotherapy is this huge buzzword right now in all of cancer. Now it can mean a lot of different things to a lot of different people. At its core level, immunotherapy means using our immune system or giving drugs that work with our immune system to help fight the cancer. If you think about things more broadly, immunotherapy is any drug that targets immune cells. And because myeloma is a cancer of immune cells, essentially all drugs that we use in myeloma are immunotherapy. But specifically in myeloma, when we think of immunotherapy, we think of three big classes of drugs. Drugs we call checkpoint inhibitors, drugs we call bifunctional antibodies, and another class of therapy we call CAR T. Checkpoint inhibitors are really interesting immune therapy drug. And the way we think about them is if I tell you you're in a car driving down the highway and I tell you to go faster, most people say, yeah, I'm going to step on the gas. Another way to think about it is to take your foot off the brake. That's how checkpoint inhibitors work in cancer. Essentially, our body has natural mechanisms to kill cancer cells, but they're held in check by these checkpoints so that they don't run rampant to attack other cells. If your immune system runs rampant, that's what autoimmune disease is, things like Shobran's disease and lupus. What these checkpoint inhibitors do is take the brake off a little bit to allow our own body's immune system to attack cancer more vigorously. It's a very exciting class of drug. Another class is the bifunctional antibodies, and we've heard of monoclonal antibodies. These are immune drugs that target something on the cell surface of the cancer cell to lock on and kill them, like a lock and key. What bifunctional antibodies do is they have two targets, one that grabs a hold of the cancer cell and one that grabs our own immune cell, a T cell, and it makes that T cell fight the cancer. It's a way of letting this drug use our own immune system to better fight the myeloma. And the final, most exciting class is something called CAR T cells. CAR T is an acronym that stands for chimeric antigen receptor T cell. In this case, we take a patient and collect their own T cells. Then in the lab, we rev them up with special technology to make them all aggressively fight the cancer. It's like taking first day cadets out of the army, putting them in special forces training and giving them bazookas. Then we take those T cells and infuse them back into the patient, and that's when they aggressively attack the cancer. So it's a way of modifying our own immune cells to better fight myeloma. This therapy was approved last year for diseases like lymphoma and leukemia, and we're hoping within the next period of time we'll have them available for people in multiple myeloma. A BECMA, a CAR T cell therapy for myeloma, was FDA approved in March 2021. CAR-VICTI is another CAR T cell therapy approved in February 2022. We're seeing a range of new immunotherapies currently being developed and hopefully becoming available for patients soon. These include monoclonal antibodies such as those that are already in use, but also T cell modifying therapies, so T cell engagers or CAR T cell therapies. So far we're seeing very, very encouraging response and also progression-free survival times. So it is very likely the vast majority of patients that are benefiting from these types of therapies. It's a very active area of disease to identify who might actually need additional intensification of therapy, but we are probably seeing one of the first kinds of treatments that on their own already have three quarters of our patients, if not more, responding just to the single agent drug. So these drugs are going to very, very likely head into our standard of care treatment. The trickiest phase of the treatment with these immunotherapies is the beginning of treatment where we do know that in some patients the immune system goes into an overstimulation, an overdrive, and that seems to be currently determining how well it can be tolerated by different patients with more or less frailty in particular. So I think this data is currently still emerging. It looks very promising in that even in older or frailer patients these treatments can be very safely administered. There is broadly no hypothetical interaction with kidney function or other organ dysfunctions that we would know classically can make treatments less safe in some patients. But some patients still require quite intensive hospital care in the first phase of the treatment, and I think it will have to be shown how much that is counterbalanced by then a very good tolerability in the long-term treatment of these patients because there these immunotherapies have very, very strong advantages over other treatments. They're generally very well tolerated in the long run, and many of them are now developed subcutaneous injections which even makes the delivery very easy. What parts of the immune system are being studied to fight cancer? There are actually studies exploring multiple components of the immune system right now. Most of the studies are on T cells, which is the sort of the soldier of the immune system if you will as it comes to cancer, but also studies that deal with B cells, with NK cells, with macrophages, and other so-called innate immune cells that exist in our bodies. So this is a very active area of research involving multiple immune cell types.