EHA 2021 | AGMT MM 02: outcomes and time to best response in myeloma

The question was whether the time to best response has any impact on outcome: progression-free survival and overall survival. So, in this study, patients are randomized to carfilzomib-len-dex or carfilzomib-thalidomide-dex for nine cycles, and then are randomized again to carfilzomib maintenance therapy for one year. They run 15 and 30, who are control.

So actually, at this point of time 97 patients have been evaluated for these parameters. And the median time to best response was actually 112 days, which is 3.7 months. And what we did is we divided the time to response of the 97 patients into different quartiles. So, quartile one was the quartile with patients with the shortest time to response. Quartile four was the group of patients with longest time to response. Longest time to response was 67, 675 days, which is 22.2 months. And the question was whether the time to response methods, in terms of progression-free survival and in terms of overall survival, and the answer is a clear yes.

So, patients with fast response to a, with a, had a… let’s put it the other way. Patients with a long time to response had a better progression significance with better progression-free survival compared to the other three groups or three other quartiles. So, the longer the time to best response, the longer the progression-free survival, whereas in the other three groups with shorter time to response there was no big difference in progression-free survival. And then, when we looked at overall survival, what we found is that those patients with shortest time to response, these were in the first quartile, these are patients with a time to response varying between 27 and 55 days. Those patients had a significantly shorter survival compared to all three other groups. In other words, those who responded very fast had a shorter survival.

And you may want to explain this probably they have different cell kinetics, probably they are fast at proliferating. So, if you come in with very active therapy, you hit those patients and those clones and in due time, but those clones tend to relapse in the usual time. So, that is something which is really interesting because in other diseases, such as Hodgkin’s disease or diffuse large B-cell lymphoma, patients with short time to response do better. In myeloma, patients with long time to best response do better. That is actually the story.

Then we try to figure out whether there are any correlations between clinical parameters. The only insignificant, let’s say, association so it’s not significant was found between fast response and highly cytogenetics. So those patients tend to have slightly higher proportion of high-risk cytogenetic features. But due to the limited patient number I would say this has not been found to be statistically significant.