My name is Doctor Jeff Matous. I work at the Colorado Blood Cancer Institute in Denver, Colorado, and we're part of the Sarah Cannon Research Institute as well. And I'm a myeloma physician.
And we've been very, very interested over the years in exploring novel treatments for myeloma, especially the bispecific and CAR-T cells. You know, the new immune therapy. So we've participated in a lot of the early phase trials with bispecific, including the majestec trial.
Now, the majestec one trial was the pivotal trial that resulted in the approval of taclistamab, a bispecific antibody to treat patients who have had many previous treatments of myeloma, and failed them. And it got approved by the FDA.
And so one of the issues with administering teclistamab is that it very frequently causes something called cytokine release syndrome, or CRS. This occurs when the t-cells, when they're attacking the myeloma, they kind of get angry and they release substances to make patients experience fever, sometimes headache, sometimes low blood pressure and just don't feel well.
And it almost always occurs in the first several days of the treatment during what we call step up dosing. Now, the way teclistamab is approved by the FDA is to give a step up dose and then a couple days later, give a little bit higher dose, and then a few days later give the full dose. And during that time that's when we see the cytokine release syndrome. But sometimes that occurs even after that.
Now cytokine release syndrome is a side effect that's made certain community hematology oncology physicians sort of hesitant to use the bispecific antibodies. And so strategies to try to mitigate the CRS and make it a little more feasible to give in the community setting, which, by the way, is where the great majority of patients with myeloma get their care. They're very important.
So in this subset, this substudy of the majestec one trial, what we did, was our coauthors is we gave the teclistamab step up dosing a little bit differently than on the FDA label. And so instead of doing three doses, we did two doses. And we increased the strength of those doses a little bit.
And the thought was, well, if we can make all the CRS occur in a very defined period of time and not have it maybe occur later and provide angst to patients or to physicians, will that make it more feasible to maybe do it in a community setting? And if you could predict when the CRS was going to occur a little more accurately.
And so that's what we did in the trials. So two different doses were used in the trial. About roughly, you know, three quarters of the patients just like before got CRS. It was all lower grade. So pretty easy to manage. About half the patients, a little more than half the patients needed a medicine called tocilizumab or toci.
So it's an antidote for CRS, if you will. But it was very feasible. And the good news from the study is that we didn't see any cases of CRS that occurred after this period of step up dose. We didn't see any after that occurred when we wanted it to occur. Nothing occurred later. It became more predictable.
Now, whether or not this becomes a strategy that we'll use to try to make teclistamab and other bispecifics more readily administered in the outpatient setting that remains to be seen.
With the higher dosing in the step up, we didn't encounter any new problems. And so neurologic side effects which are quite rare remain quite rare. Infections weren't more common. Low levels of antibodies called hypogammaglobulinemia that wasn't more common.
And the study didn't look at efficacy. But efficacy won't change because the long term treatment is the same. Now, I should add this. And in these subsidies of majestec one, the way the teclistamab is administered is very rapidly to go to every four week dosing, which is differently than the FDA label where it's weekly dosing. Every four week dosing, we think, is going to be effective, associated with fewer side effects.
And way easier for patients, of course. And so there were no new safety signals at all. So it definitely, I think, in my opinion, would be an alternate way to do step up dosing.
So toxicity, I think that there's a lot we don't know still about how to give the bispecific antibodies in myeloma. And one of the things we don't know among many is what's the right schedule, can we stop them ever, etc., etc.. So a lot still to be learned.
Patients, with their physicians, and they are considering bispecific therapy in myeloma, need to, I think, be aware of a few things. One is okay, is this the right therapy for me? Is there a clinical trial where maybe they're looking at something different or a combination?
That might be a good idea for me. We have different bispecific, right? We have different bispecific to target different parts of the myeloma. And they differ as well in certain areas. So lots of questions to ask there.
But if I'm a patient looking at bispecifics, I want to know hey can I do this outpatient? And if I do, what do I do if I get that CRS, how are we going to manage that? And then long term, what's my schedule going to be?
And, and if I'm a patient, I'm going to say, hey, doc, what are you gonna do to try to lower my infection risk? Certainly for the BCMA bispecific. So that's been the biggest concern for physicians is long term infectious risk as well.
In this study, majestec one, with you with the higher dose step up dose into the teclistamab analysis administered as monotherapy, that is all by itself, not in combination. Other majestec studies, for example, majestec two, majestec five, etc., etc. these studies just keep going are exploring combinations.