ASH 2023 | MonumenTAL-2: talquetamab plus pomalidomide in R/R multiple myeloma

I’m excited about that. So, this is an international study where we looked at patients who had recurrent multiple myeloma after having received at least two prior regimens, including an anti-CD38 monoclonal antibody and an immunomodulatory drug, including pomalidomide, in some cases. And so patients had a median number of prior therapies of three, and when they were enrolled, they had to have, you know, reasonable performance status and measurable disease, the usual things. All patients received talquetamab, and they either could receive it at weekly dosing or every other week dosing, which is pretty standard for the agent. And then, pomalidomide was added at cycle two, and pomalidomide was added at two milligrams daily and investigators had the option to increase the dose to four milligrams daily at their discretion. Patients were treated until disease progression or side effects dictated otherwise. 

What did we find in the study? We found that response rates were really high, roughly 90%, and many of the responses were deep, that is stringent complete responses, and complete responses were quite high, including about 65% in the weekly dosing schedule, which has longer follow-up. Their responses were durable, for the most part, and we’re seeing this across all disease risk categories, including extramedullary disease. So I found that really exciting. When you think about that response rate with combining talquetamab with pomalidomide and compare it, for example, to carfilzomib/pomalidomide or daratumumab/pomalidomide, response rates, at least comparing across trials, I think are very impressive. So very encouraging. 

So what were the downsides of that? What were the adverse events and so forth? Well, they were typical of what we often see with each of these agents. So for talquetamab, we saw dysgeusia in virtually all patients and the talquetamab actually resulted in side effects that required a dose hold in about three-quarters of patients and a dose modification in almost half of patients, which could be either dose or schedule of the talquetamab. Now, for pomalidomide it was the typical cytopenias, so neutropenia and so forth and high-grade neutropenias were common but neutropenia infections were very uncommon, so I think that was quite tolerable. CRS was seen in three-quarters of patients, just like we’ve seen before with these agents. Managed about half of the cases with tocilizumab. So I think here we have an agent that is… a combination of two drugs which has never been done before, to my knowledge. Talquetamab and an IMiD, in this case pomalidomide, showing very high response rates, manageable toxicity, and warrants further investigation and, I think, holds a lot of promise for our patients.