Talquetamab + Pomalidomide in Myeloma: MonumenTAL-2 Safety & Efficacy | Jeffrey Matous, MD |ASH 2023

My name is Dr. Jeff Mattis and I'm a member of the Colorado Blood Cancer Institute in Denver, Colorado, part of the Sarah Cannon Research Institute. And I'm going to present some data from the 2023 ASH meeting that I think are really exciting and hold, I think, promise for the patients who have recurrent or relapse multiple myeloma. And what we're going to talk about at our abstract here is combining two medications that have never ever been combined before for the treatment of people who have recurrent myeloma. Now, one of those is an old friend called pomalidomide, also called an immid or immunomodulatory drug. The other is a relatively newly FDA approved medicine called talcuetamab, which is a GPRC5D, try tackling that one, redirecting T cell antibody or bispecific antibody. So talcuetamab has already been approved by the FDA to use all by itself for patients who have multiply recurrent relapse refractory multiple myeloma. So in our study, what we did, and this was an international study of myeloma investigators, is we enrolled patients who had at least two previous treatments for myeloma. On average, most had had three and they'd been exposed to the image like linalytomide or even pomalidomide. And they'd been exposed to CD38 antibodies such as Darzelex or daratumumab, and they were in need of therapy. And so these patients all received talcuetamab, which is given either weekly or every other week along with daily doses of pomalidomide. And the pomalidomide wasn't added until the second cycle just to be sure that everything was okay. And then what we followed in these patients, we followed a couple things. One is efficacy, did it work? And almost as important, if not more importantly, how did the patients tolerate it? Let's talk about efficacy first. So what we found is that when we combined talcuetamab with pomalidomide, the response rates were really, really high in the 90% ballpark. And those responses were mostly really, really good, almost rending the myeloma undetectable by our standard techniques. That's called complete response. And what we found is that with the side effect profile, we found side effects typical of both of the agents. And so both these agents can cause lowering of the blood counts. That's something that has to be monitored. And a lot of patients required modification of the dose of pomalidomide to counteract the lowering of the blood counts. And for talcuetamab, the typical side effects that we look out for are ones that involve the sense of taste. That's called dysguisia, skin rash, or fingernail findings. About three quarters of patients needed to have their dose held for a while to manage that side effect. And almost half the patients had to have the dose altered or the schedule changed a little bit to manage that side effect. But it was feasible, and very few patients had to quit this study because of side effects. Only four of the 35 patients had to do so. So I think we're onto something here. I think we have a good combination that merits further explanation for patients with recurrent myeloma.