Carfilzomib Dosing in the Real World Setting | Adeel Khan, MD | IMS 2024

Hi, my name is Dr. Deol Khan. I'm an assistant professor at the University of Texas Southwestern Medical Center in Dallas, Texas, and I focus on multiple myeloma. And here at the International Myeloma Society in Brazil in 2024, my group and colleagues presented an abstract looking at the carfilzomib dosing. So carfilzomib is a proteasome inhibitor. It's one of the three. In terms of popularity, there's bortezomib, there's carfilzomib, and then there's exaxomib. And carfilzomib is arguably the most potent. We heard that for a number of years now, but there has never been decided the optimal dosing schedule for it, nor the optimal dose itself. And so my colleagues and I took real world data to try to approximate an answer to this. We know from previous trials that there are several dosing schemes. There's 70 milligrams per meter squared once weekly, 56 milligrams per meter squared twice weekly, 56 milligrams per meter squared once weekly, 27 milligrams per meter squared twice weekly, and so on. And with such dosing schedules, there is no consensus as to what really ends up being the most superior. And to be clear, they're all technically valid. They're all supported by clinical trial data. But in the real world, we'd like to see, can we come up with perhaps a better answer to establish a new standard? So what we did was we looked at real world data using the Flatiron database. Flatiron is a nationally representative database of multiple myeloma patients all across the U.S. And we looked at several different dosing schemes, a few of which kind of rose up to the top as being the most for consideration. We looked at 70 milligrams per meter squared once weekly, 56 milligrams per meter squared twice weekly, 56 milligrams per meter squared once weekly, and then in some other analyses, well, the 27 milligrams per meter squared dosing schemes. And then we looked at what are the outcomes when people are treated this way in identifying the patients of who would be in this study. We focus on people who were getting treated with the second line or beyond. And so this was not newly diagnosed. This was at least one line regimen afterwards. And whatever the companion drugs were, all were acceptable for this. The outcomes that we wanted to focus on were overall survival and progression free survival, being the outcome of death versus not and progression free survival being the outcomes of death progression of the disease or not. And in running the analysis, we did a multinomial survival analysis using conventional methods. When we did this, we then identified 500 patients roughly nationally who were included in the study. And in then crunching the numbers, what we found was there was no significant disparance in these dosing regimens and schemes. That is to say, we found a relative equivalence between the 70 milligrams per meter squared, the 56 milligrams per meter squared twice weekly, and the 56 milligrams per meter squared once weekly. And looking at the actual survival analysis curves for the overall survival and the progression free survival, they overlap very significantly. That is to say, there was no suggestion from this data that there was really anything different between them. When we sort of looked beyond the data and looked at such things as financial toxicity, logistical toxicity, the other burdens that come with treatment, including side effects, we then make the argument that the 56 milligrams per meter squared once weekly dosing is perhaps the optimal. It is in fact the sweet spot. It is not twice weekly, so it is less burdensome. It does not have the side effect profile that the 70 milligrams per meter squared dosing scheme has. And so we found that it sort of fulfills several checkboxes in terms of what ends up being seemingly the best. To be clear, this does not prove that it is in fact the best. This is just one look at what we could try to approximate an answer to that question. And we make the suggestion then that for ongoing clinical trials that perhaps the 56 milligrams per meter squared once weekly dosing should in fact be the standard.