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Emerging Therapies in Multiple Myeloma

— Joseph Mikhael, MD, discusses the CAR-T cell therapy trials from ASH 2020

MedpageToday

CAR T-cell therapy is poised to transform the treatment paradigm of relapsed/refractory multiple myeloma now that multiple approaches are demonstrating impressive results.

In this exclusive 51˶ video, , of City of Hope Cancer Center in Duarte, California, discusses the promising clinical trials in cellular therapies for multiple myeloma that were presented at December's American Society of Hematology (ASH) virtual meeting.

Following is a transcript of his remarks:

Hello, this is Dr. Joseph Mikhael. It's a pleasure to share with you some of the really exciting emerging therapies that we have in multiple myeloma that have been presented at this year's annual meeting of the American Society of Hematology. There's so many different compounds to talk about, but I'm going to simplify it to two major classes, or approaches that we know are really going to heavily influence the way we treat multiple myeloma.

And the first of these are CAR-T cell trials. So we know that CAR-T cell therapy has already significantly impacted the lymphoma and leukemia worlds, but we saw almost innumerable trials now in multiple myeloma, using different targets as well, but primarily the BCMA target.

And the two studies that perhaps I'll highlight quickly, was the KarMMa trial with the product bb2121 -- which quite likely will be the first drug approved or first approach approved using car-T cell therapy in multiple myeloma -- where we saw three quarters of these heavily pretreated patients responding with a progression free survival longer than their expected survival before this of nine or so months, but even overall survival extending over a year and a half. So quite impressive results. And secondly, the CARTITUDE study, with a cilta-cel product, where we're seeing now response rates even higher over 90%, with quite manageable toxicities of cytokine release syndrome. So I really think that we're going to see CAR-T cell therapy for myeloma in the next year. And it really has, I think, a prolific impact initially in the heavily pretreated, and then maybe brought up a little bit earlier.

There is also a whole other class of drugs that are sometimes called the bi-specifics. These are monoclonal antibodies that are called bi-specific or occasionally tri-specific because they have two arms, if you will. One arm hooks onto the tumor typically by BCMA, and the second arm reaches to a local T-cell and engages it to destroy the cell. And the remarkable developments at ASH this year, were that we've seen further advances in these agents, but not only longer term data with significantly safer signal, in that very few patients experience any significant cytokine release syndrome, although patients are given the first dose in hospital and the rest as outpatient. But also efficacy rates that are pushing 50, 60, 70, and even 80%. So it was really quite remarkable with, with products like teclistamab and tocilizumab and AMG701 are the three most far along. But the other point to make is they're not just BCMA directed now, we have other targets like GPRC5D and FcRH5. So we're discovering new targets in myeloma that we can latch on to, to engage the T-zone.

So these aren't quite ready for prime time yet, but I suspect that we're going to see them in our armamentarium for treatment of myeloma in the very near future.

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    Greg Laub is the Senior Director of Video and currently leads the video and podcast production teams.