KRd versus VRd in patients with newly diagnosed multiple myeloma

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Published: 6 Dec 2018
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Dr Ola Landgren - Memorial Sloan Kettering Cancer Centre, New York, USA

Dr Ola Landgren speaks to ecancer at ASH 2018 about the results from a study into carfilzomib-lenalidomide-dexamethasone (KRd) versus bortezomib-lenalidomide-dexamethasone (VRd) in newly diagnosed patients with multiple myeloma.

He explains that the CoMMpass study, launched by the Multiple Myeloma Research Foundation (MMRF), can be used to identify patients treated with the KRd and VRd regiments.

Dr Landgren reveals that the event free survival is highly superior for patients treated with KRd.

ecancer's filming has been kindly supported by Amgen through the ecancer Global Foundation. ecancer is editorially independent and there is no influence over content.

I’m presenting here at ASH 2018 a study looking at newly diagnosed patients treated with a KRd regimen, or carfilzomib, lenalidomide, dexamethasone, compared to patients treated with the VRd regimen, or bortezomib, lenalidomide and dexamethasone. We are using the CoMMpass study which is the initiative that was launched in 2011 by the Multiple Myeloma Research Foundation, MMRF. Using this resource we identified all the patients treated with a KRd regimen and there were many more patients treated with VRd because that’s an older regimen. So we took the approach of designing a nested case control design. So for each patient treated with KRd we identified a matched control with a propensity scoring approach. Then we looked for clinical outcomes.

The main results show that the event free survival is highly significantly superior for patients treated with KRd. The hazard ratio is 0.35, so it’s a 65% reduced risk of the adverse outcome in the KRd patients. The study had about 150 with KRd and about the same number, 150, with VRd because it’s the matched nested case control study.

Because this is not a clinical trial that is randomised, this is a cohort study using the CoMMpass study as the resource, so you identify the first group for cases, this is the KRd regimen, and then you look within the database to see how you can find matched controls which is the VRd patients. So, therefore, there is no capturing every cycle by a protocol, these are patients from the real world around the world. So what we had to do in order to get a better understanding of toxicities we decided to look at adverse events that resulted in discontinuation of the treatment. It’s important to say that in this real world resource from the CoMMpass study the adverse events that resulted in discontinuation of therapy was very, very low, it was around 2% and it was virtually the same for the two treatment arms.

So the conclusion of the study is looking at event free survival using the CoMMpass study as the resource, that the KRd regimen is highly more superior in terms of progression free outcome. This is matched event free survival, so that means that the risk both of progression, the risk of death and the risk of having to change therapy, that’s the information that goes into event free survival, it’s highly superior in KRd. It’s actually 65% reduced risk compared to the VRd regimen.
I think it’s important to say that this is not a clinical trial so if you stick to the standard approach for validation of what data is going forward we should probably wait and see what a randomised prospective study will show. There is actually an ongoing study here in the United States comparing the KRd regimen with the VRd regimen. This was funded by the National Cancer Institute, this is a federally funded study.

In addition to the main message that the event free survival is highly significantly better for KRd, a hazard ratio of 0.35, we also looked to see if patients were transplanted after the combination or if they were not and then we conducted stratified analysis. The information from the study is that the hazard ratio is virtually the same if patients receive this combination, KRd and a transplant, or VRd with a transplant, the hazard ratio is again in favour of KRd. If patients were not transplanted the same thing applies – the hazard ratio is strongly in favour of the KRd regimen.