Linvoseltamab -Now Approved- Know Your Therapy Video is in production

Lymphoceltumab is an investigational bispecific antibody being studied in patients with multiple myeloma. Lymphoceltumab binds to B cell maturation antigen or BCMA on the surface of myeloma cells. It also binds to CD3 on the surface of T cells. By linking T cells to myeloma cells, it can elicit an immune response directed at the cancer. BCMA is an ideal target for multiple myeloma since it's almost exclusively expressed on plasma cells. Plasma cells are the type of cell that are myeloma cells. It is expressed to a very low degree on other cell types but not to a significant extent such that we would have a lot of side effects when those cells are targeted. So it's primarily just the myeloma cells and the healthy plasma cells that are targeted. Lymphoceltumab is being investigated in a clinical trial and in that study intravenous Lymphoceltumab is given once a week and it was done that way for 14 weeks. After that, patients can reduce the frequency of Lymphoceltumab to every other week. In some patients achieving a very good partial response or better, which means a 90% reduction in the monoclonal protein, the drug is infused once a month. So Lymphoceltumab is infused over four hours but it can be reduced to two hours and subsequently one hour if the patients aren't experiencing any cytokine release syndrome. It is given in a step-up dosing. The purpose of the step-up dosing is to gradually initiate the therapy so that if patients are experiencing cytokine release syndrome, the symptoms are not as severe. The step-up dosing works as follows. Patients are given the dose twice, one week apart. The first dose is administered in the hospital with 48 hours of observation after the administration of the drug. Patients go home as long as they're not experiencing any side effects. The following week, they come back to the hospital and receive a second dose. There, they only have to be observed for 24 hours. If the patients are doing well with that second dose, they can move on to the full dose. The full doses are given outpatient. The recommended full dose is 200 milligrams and it's given weekly, intravenously in the clinic. So during the step-up dosing, we do recommend pre-medications. We usually give dexamethasone, Benadryl, and Tylenol. If patients are doing really well without any cytokine release syndrome, those pre-medications can be discontinued at the discretion of the physician. Lymphoceltamab, like other bispecific antibodies, is off the shelf, meaning it does not require patients' own cells to be manufactured, which is the case for CAR T-cell therapy. But it works very much like CAR T-cell therapy in that it's eliciting a T-cell response against myeloma. Because it is off the shelf, one of the advantages is it can be administered very quickly at the time the need is determined, whereas a CAR T-cell can take up to three weeks to be manufactured. The primary side effect of Lymphoceltamab is cytokine release syndrome. In the Phase I-II clinical trial, 46% of patients experience cytokine release syndrome. Cytokine release syndrome is a flu-like illness with fevers, chills, sometimes low blood pressure. This must be monitored and treated in the hospital. We can treat mild cases with just Tylenol, but more severe cases require an infusional drug called tociluzumab. Lysolumab is an anti-IL6 therapy that calms down the immune system and reverses some of the side effects of cytokine release syndrome. The majority of the cytokine release syndrome is Grade I and II. We don't see very many of the higher grade cytokine release syndrome. About 8% of patients receiving Lymfoceltamab do experience some neurologic toxicity, which is on par with the other bispecific antibodies. Lymfoceltamab is being studied in a Phase I-II clinical trial known as the LINKER study. In this study, there were approximately 235 participants and patients were followed for a median of 11 months. And at the time that the data was reported, 71% of patients achieved an overall response, with 46% of patients achieving a complete response or better. This is very similar to what we're seeing with the other bispecific antibodies that have been FDA approved. Lymfoceltamab is being studied as a single agent, not combined with other drugs, but in the future it will likely be combined with other therapies, depending on how it goes. The Lymfoceltamab was studied in a clinical trial in which patients had three prior lines of therapy. This had to include a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoplonal antibody. Proteasome inhibitors include carfilzomib, bortizomib, or hexazomib. These are older agents that work by inhibiting the proteasome inside of myeloma cells, which is the protein factory. Immunomodulatory drugs include lytalidomide, pomalidomide, and thalidomide. And these are drugs that activate the immune system, directing T cells and NK cells in a non-specific way to fight cancer. Anti-CD38 monoplonal antibodies include daratumumab and esatuxumab, and these are antibodies that bind to CD38 on the surface of myeloma cells and elicit a direct immune response to the cancer. In February of 2024, the FDA approved an application for priority review of lymosaltamab. This means that instead of the regular 10-month review process, it will be reduced to six months. So hopefully, by the end of this year, we will have some results in terms of the recommendations of the FDA for approval of lymosaltamab. I think the big difference between lymosaltamab and the currently available anti-BCMA bispecific antibodies is lymosaltamab is given intravenously, whereas the others are given subcutaneously. However, lymosaltamab can potentially be given once a month in patients who have achieved a very good partial response after the first 14 weekly doses. So that's a particular advantage. And finally, the cytokine release syndrome rate is around 46% compared to the other approved bispecific antibodies, which is closer to 70%. So even though it targets the same protein on myeloma, there are some advantages to lymosaltamab compared to the other therapies.