LINKER-MM1 Study: Linvoseltamab (REGN5458) in Relapsed/Refractory Myeloma | Hans Lee, MD | ASCO 2023

Hi, my name is Hans Li. I'm a myeloma physician from M.B. Anderson Cancer Center in Houston, Texas. And today I'm going to be talking about the LINQR-MM1 study with lymphocytoma in relapsed refractory multiple myeloma. So lymphocytoma is a classic drug called a BCMA bispecific T cell antibody. Or basically one arm of the antibody binds to a myeloma cell and the other arm of the antibody binds to a T cell or immune cell and brings the T cell and myeloma cell in close proximity and leads to hopefully a lot of myeloma cell killing. And so lymphocytoma has shown encouraging efficacy and safety in earlier results presented regarding the drug. And so the phase two part of the LINQR-MM1 study is evaluating two different doses of lymphosultimab at either 50 milligrams or 200 milligrams to optimize the dose selection. So at this year's ASCO and EHA meeting, we are presenting for the very first time the initial results of the fully enrolled phase two part of the study at both the 50 milligram and 200 milligram cohorts. So patients who were enrolled on this study had heavily resistant refractory multiple myeloma. They had at least three prior lines of therapy, including Paris inhibitors, immunomotor drugs or anti-CD38 monoclonal antibodies. Or they had myeloma that was refractory to all three classes of drugs, regardless of lines of prior therapy. And patients enrolled on study then received lymphosultimab intravenously, initially with two small step up doses of five milligrams and 25 milligrams dose one week apart with a 24 hour hospitalization after each of the step up dosing. And this was basically done to mitigate the risk of something called side kind release syndrome, which is a potential side effect of the bispecific T cell antibodies. And then subsequently patients received either 50 milligrams or 200 milligrams of lymphosultimab weekly for the first three cycles, which was then deescalate every other week for cycles four and five. And patients enrolled on the 200 milligram cohort could then undergo further deescalation in a response adaptive approach to every four week dosing if attaining something called a very good partial response or better. And so patients who enrolled on the phase two part to the linker MM1 study had many, many prior treatments for their multiple myeloma. Specifically on the 200 milligram dose cohort, patients had a median of five prior lines of therapy. Only three fourths of patients were triple class refractory, meaning that they were factory or they had myeloma that was refractory to prison inhibitors, immunologic drugs and anti CD 38 monoclonal antibodies. And 36% of patients in the 200 milligram cohort also had high risk fish or high risk side genetics and 27% of patients were over the age of 75 years of age. And so the results demonstrated that the over response at the 50 milligram dose cohort was 50%. And at the recommended 200 milligram dose cohort, the over response rate was 71% with 59% of patients attaining a very good partial response or better and 30% of patients attaining a complete response or better on the study. And the responses seemed durable. And so response seemed to deepen and over time as patients continued on therapy and The six month probability of maintaining a response in patients who initially respond to therapy was 84%. And the median progression free survival, which is based on the amount of time that the myeloma remains under control, had not been reached at a median follow up of 5.6 months and the 200 milligram cohort. And the six month probability of progression free survival was 73% on the study. In terms of side effects, the most common side effect of lymphosultimab on the linker MN1 study was something called cytokine release syndrome, which is basically when the immune system activates and potentially can cause symptoms like fever and more severe cases, low blood pressure or oxygen, low oxygen levels requiring supplemental oxygen. And so we were encouraged that the rates of CRS were generally relatively low. So 45% of patients had cytokine release syndrome who were dosed on the 200 milligram cohort. The majority were what we call grade one severity, which was the lowest severity, which typically manifests as a fever, which occurred in 35% of patients. And 9% of patients on the study had what we call grade two CRS. And so we're very encouraged and very excited about the results of the linker MN1 study. It does demonstrate that lymphosultimab has high efficacy and with deep and durable responses in patients who were dosed with lymphosultimab on the linker MN1 study. And importantly, it also showed high responses in key high risk subgroups of patients, including patients with high risk multiple myeloma and patients with high baseline disease burden. And so, you know, lymphosultimab we think will represent a promising approach among BCMA targeted therapies. I think some of the things that potentially are particularly encouraging of lymphosultimab include the fact that their CRS rates are relatively lower, cytokine release syndrome rates are relatively low. And there's very overall limited hospitalization required to administer lymphosultimab as it only requires a 12 hour hospitalization after each of the initial first two step up doses. Infections in general have been a particular adverse event of special interest among by specific antibodies in general. Overall the rates of infection were similar between the 50 milligram 200 milligram cohorts of lymphosultimab. Approximately 60% of patients experience infections on one dose of lymphosultimab. About 35% of patients had more severe infections we term grade three or grade four infections. And opposite infections were more rare atypical infections occurred in 2% of patients dose in the 50 milligram cohort and 8% of patients dose in the 200 milligram cohort. So infection management is really, really important when considering the use of by specific T cell antibodies in general. And there's several key important steps. So one is infection screening and infection prophylaxis. And so it's important to screen for potential common pathogens that may be relevant when a patient's being treated with by specific antibodies in general. Things like CMB hepatitis B, hepatitis C. And once starting treatments with a by specific Then we would consider varicella zoster prophylaxis with their acyclovir or valacyclovir as well as PGP pneumonia prophylaxis with Bactrim most commonly. In addition, vaccinations also important as well in patients receiving by specific antibodies and myeloma therapy in general. And so staying up to date on flu vaccine, pneumonia vaccine and COVID-19 vaccines are also important mitigation strategies. And finally, we also note that hypogammaglobulinemia, which is basically having a low IgG level or normal antibody levels in the body to help fight infections is common with the by specific antibodies. And so we often would administer something called IVIG or intravenous immunoglobulin to help support the immune system. Thank you for listening.