All-Oral Myeloma Combo: Mezigdomide + Tazemetostat or Trametinib | Paul Richardson, MD | EHA 2025

My name is Dr. Paul Richardson and I am the clinical program leader and director of clinical research at the Jerome Lippa Multiple Myeloma Center at the Dana-Farber Cancer Institute in Boston, Massachusetts. So at the meeting here, it was been a pleasure to be part of a remarkable study team led by my colleague Luciano Costa. And we presented data at this meeting from the team regarding our combination of mesigdemide and dexamethasone with really novel oral agents. On the one hand, Tazamizostat and on the other hand, Trimetinib. These are oral agents that specifically target important biological pathways in myeloma. And suffice to say that both of these pathways are important in myeloma pathobiology. And so the idea is that by combining mesigdemide, which is what's called a potent cell mod, which is extremely important in targeting myeloma directly and at the same time activating the immune system against myeloma, where these other small molecules can overcome pathobiologic resistance of the myeloma and that we see as the disease becomes more advanced. And the good news from our study is that this has not only been confirmed with high response rates both for the combination of mesigdemide, dexamethasone and Tazamizostat at between 60 and 70 percent and for mesigdemide, dexamethasone and Trimetinib with response rates between 75 and 80 percent. These responses have been sustained and durable. And what's I think particularly exciting is that the safety profile has also been favorable. And at this particular meeting, we've also shown that immune subsets, particularly amongst T cells, are enhanced by the use of the mesigdemide in particular. So really nice data supporting an all-oral option that has been shown to be remarkably active even after potent immune therapies like CAR T cells and indeed by specific antibodies have unfortunately failed the patient. So we're very excited by this and looking forward to next steps and future directions with mesigdemide both in these kinds of settings and more broadly as the current phase three studies testing mesigdemide against standards of care continue to enroll and in fact generate data we hope that will be meaningful relatively soon, recognizing that some of these large phase three trials have already completed enrollment. So we're very hopeful that we'll be able to bring very important data regarding mesigdemide to the myeloma community later this year, if not early next year.