Predictors of delayed responses to teclistamab in myeloma | Rahul Banerjee, MD | IMS 2024

Hi everyone. My name is Rahul Banerjee. I'm an assistant professor of medicine at the Fred Hutchison Cancer Center in Seattle, Washington. I'm here live at the IMS meeting, the International Myeloma Society meeting in Rio. And one of the many posters I presented was a work from our U.S. Myeloma Consortium, our immunotherapy consortium, looking at predictors of delayed responses to Toclistumab, Pecvelia, a bispecific antibody. So first, a little bit about the consortium. I think it's really important that we combine our resources together. As many of you know, physicians are often not very good at working together on research projects, collaborating, sharing data. We're trying to change that with the U.S. Multiple Myeloma Immunotherapy Consortium. Dr. Hansen at Moffitt, Dr. Siddana at Stanford, and Dr. Patel at MD Anderson are our leaders for this. And so we actually looked at 400 patients or so who had received Toclistumab, Pecvelia, a bispecific antibody for multiple myeloma. And we looked at basically how they did. Most patients, if you look both in the trials and in real world experience, the time to first response is 1.1 months. That means that when you start a bispecific antibody, so again, Toclistumab, Pecvelia, L-Renatumab, L-Rexfeo, Talquetumab, or Talve, and more are on the way, you typically, if it's going to work, it works quickly. If it doesn't work, it doesn't work, and then we move on to something different. I have had patients where we check the labs on cycle two day one, so about a month in, the light chains haven't really come down. They haven't come down 50% yet, and we're stuck with this dilemma, kind of like this 80s song, do I stay or do I go? Trying to figure out what to do with these patients because they're impatient, I'm impatient, this is their life on the line here, trying to figure out do we stay with the bispecific for longer or do we try to move to something different? And so what we did is we tried to look at predictors of delayed responses, patients who did not have a response, meaning a 50% reduction in the M-spike or light chains, et cetera, by one month, who later went on to have a response of three months. And then briefly, we found that patients who had a preserved absolute lymphocyte count, an ALC value that was normal, and had had CRS, cytokine release syndrome, the fever that can happen was bispecific, it had to happen early, about half of them actually went on to have a response versus those who had neither, very few of them went on to have a subsequent response. This is obviously a very technical abstract, and I would say if you're listening to this, talk with your physician, and you're on a bispecific, talk with your physician about it, because I think it's a very relevant question to have. I think we're seeing more and more on the data being presented here, for example, that there's a discrepancy between progression free survival and duration of response, meaning that with a bispecific antibody, when it works, it works very well. And when it doesn't work, it doesn't work. And there's not much of it in between. Obviously, we're trying to fix that as a field and make it work for everybody and make it work for longer and longer, regardless. But in the absence of that, I would say, you know, if you're reading this, watching this video in a cycle two day one, you're a month into a bispecific and the light chains haven't come down the way that you would like, you're disappointed, very understandable to be disappointed. Talk with your physician, maybe have them take a look at our abstract and they can calculate in your case the risk of having a subsequent response versus should it be time to move on to something different. Either way, again, this is a function of real world data, has its limitations, and hopefully, again, as we get bispecifics to more patients, as we get better with dosing them, as we combine bispecifics together, which I think is an intriguing possibility, or combine it with homilidomide, or there are two of them, or existing medications, hopefully that response rate, that quick divide between who has light chain reduction and who doesn't will start to disappear.