LINVOSELTAMAB in Patients with Relapsed/Refractory Myeloma | Suzanne Lentzsch MD, PhD | EHA 2024

Hello, my name is Susanne Lench. I'm a professor of medicine at Columbia University in New York. I'm here at IHA 2024 and I presented today data on a drug which we call Linvuzeltamab. It's a bispecific antibody. So this bispecific antibody binds to multiple myeloma cells and it also binds to T cells. So the antibody, we call those antibodies bispecifics because they bind to cells, bind to a marker we call BCMA. BCMA is expressed on the surface of the myeloma cells. It's a little feature that the bispecific antibodies can bind to in order to recognize a myeloma cell. They also engage the T cells. That means the T cell, which is a good cell from the immune system, can directly kill the multiple myeloma cells. So you have to imagine the bispecific antibodies are little tools to bring the T cells to the myeloma cells to killing the myeloma cell. So those bispecific antibodies have been used in the past very successfully. The overall response rate of those bispecific antibodies are around 60%. Today I presented data on a third bispecific antibody. We already have approved Teclistamab and Alvanatamab. Hopefully Linvulzeltamab, this is the one I will present today, will also be approved soon. So historically those patients treated with bispecific antibodies are heavily pre-treated. That was also the case in the Linvulzeltamab trial. The patients had an median five prior lines of treatment. Some had even up to 18 different lines of treatment. The treatment schedule of this drug included the patients who were triple class exposed. That means they had a PI, a proteasome inhibitor, in a mutamodulatory drug such as lenalidomide and CD33 antibody such as teratumumab were included into the clinical trial. The patients received initially the treatment weekly for altogether 14 weeks. After 14 weeks the interval could be decreased and patients received the treatment every other week. So that was very nice. After 24 weeks if patients had achieved a VGPR, a very good partial remission or better, they could switch to a monthly treatment which made that schedule very convenient. Also there was a different patient population. The median age was 70 years and we had a patient population of around 26 percent of the patients who were even older. They were 75 years. So that means it's a medication we can use in our older patient population and in addition we also had a lot of patients who are so-called high risk multiple myeloma. That means they had extra modulary multiple myeloma, they had high infiltration rate, they had a higher stage of the international staging system, that means stage three. So altogether it was a very heavily pre-treated patient population and the results are very encouraging. We saw that in this heavily pre-treated patient population the overall response rate was 71 percent. That means the majority of the patients responded and showed a decrease in their m-spike. Half of the patients, 50 percent, had a complete response. That means the myeloma protein disappeared completely and also the bone marrow was free of disease. So that was extremely encouraging and when we look for the MRD negativity, the minimal residual disease negativity in the bone marrow, we observed that 93 percent of the patients who had a complete remission were also MRD negative. So extremely encouraging data and we are very excited about that. But I also want to talk about the side effects. So usually we are concerned about IRS, the infusion related syndrome. That means as you develop fever for instance, low blood pressure and also need oxygen, then you get those by specific antibody infused. What we observed was also encouraging the majority of patients had only grade 1 and 2 CRS and around 45 percent. Only 1 percent of the patients had a higher grade CRS. That means they needed some support with oxygen for instance or medication to increase the blood pressure. So in terms of the CRS, the cytokine release syndrome, also the treatment is very well tolerated. But we still have another problem and those are the infections and that I think is the biggest problem we have in the by specific antibodies. Those infections occurred in 75 percent of the patients and around 35 percent of the patients had a grade 3 and 4 infection. That means it was an infection that needed antibiotics and some of the patients needed infusions and had to be admitted to the hospital. So 35 percent is a lot and what our conclusion was, it is a very powerful drug but infections are too high. So we need to give supportive care for our patients. That means everybody who is on a by specific antibody should receive IVIG, intravenous immunoglobulins and should also have prophylactic prophylaxis. We saw that with those measurements, the infection rate really decreases dramatically. So altogether a very promising third by specific antibody that results in really high response rates, 50 percent CR, with 93 percent of those patients MID negative, relatively well tolerated, but we need to keep an eye on the infection. Thank you so much.