As Terry pointed at, treatment with Kyprolis, Revlimid, and dexamethasone (KRD) is not the initial topic. However, it did touch on the idea of consolidation and extended maintenance.
Firstly, the second Jakubowiak study on KRD with an autologous stem cell transplant (ASCT) I would like to point is a valid study accepted by the authorities. I point this out because Terry did such a good job of stating the things that the study DID NOT do, that it reads as if it is a flawed study. Quite the contrary. There are other studies out there, head-to-head comparative studies, that were more directly the basis of the approval of Kyprolis, that addressed some of the points that Terry had made. Dr. Jakubowiak's study is actually credited as being very innovative and forward thinking by his peers.
As a practical manner, it would be so hard to do focused studies on individual adverse cytogenetic abnormalities (CAs), particularly at a single center, that these studies would never get done due to the small populations. Studies on adverse CA's are mostly done in a "pooled manner". It is difficult to get the critical mass to do really good studies on adverse CA's, though many doctors point out that this is a great need.
The central idea behind the study, as I recall the doctor stating, is that based on early study designs showing the success of KRD, what if it were "maxed" out, and done in the setting of initial diagnosis (initial drug approval is typically done in the relapsed/refractory setting). For those who suspected that Kyprolis was going to be good, if you signed up for the study, there was a 100% chance that you get the new drug. That was a big advantage, quite different from a "head to head" study. I think the issue was expected to be whether or not the patients could tolerate the proposed regimen. The doctor expected that it would be successful in terms of deeper response.
In terms of response, the doctor was indeed right, as the minimal residual disease (MRD) negative rate turned out to be in the range of 80%, far in excess of anything before. Based on published results where half of the people in CR were MRD positive, the prior best published rate for MRD negative for first line of treatment was in the range of 25% (my estimate, only recently have studies specifically documented that rate).
Very generally, you could not improve the overall response rate and progression-free survival by that much of a margin by not improving the total group of adverse CA's, which in total represent about 40% of all newly diagnosed patients.
Now the regimen included a newer induction drug, increased consolidation, and increased maintenance. Is it possible to tell which exactly of those three variables is which in terms of the improved response? I would say probably not. However, that would be missing the point. The overall response rate leapfrogged by a good deal anything before it. This can be improved further over time with more precise studies. I think, however, it is appropriate to give credit where its due.
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