A phase 1b study of once-weekly KRd in patients with newly diagnosed multiple myeloma

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Published: 25 Sep 2019
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Prof Ola Landgren - Memorial Sloan Kettering Cancer Center, New York City, USA

Prof Ola Landgren speaks to ecancer at the 2019 International Myeloma Workshop meeting in Boston on a phase 1b study of once-weekly KRd in patients with newly diagnosed multiple myeloma.

He explains that the study was designed to decipher which was the safest dose, with the weekly dosing of 56mg/m2 once a week deemed the safest and most efficacious dose.

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 was the presenter of the weekly KRd with weekly carfilzomib in combination with lenalidomide and dexamethasone in newly diagnosed multiple myeloma patients. This was part of a protocol that included both newly diagnosed and relapsed multiple myeloma patients. My presentation was focussing on the newly diagnosed patients.

In brief, the study was designed to explore which was the safe dose and we tried different types of dosings. We did 56mg/m2, we also did 70mg/m2. Eventually the results indicate that the weekly dosing of 56mg/m2 once a week is the safe dose, that’s also the efficacious dose. So together with lenalidomide that’s how patients should be treated. On a practical note 20mg/m2 day one of the first cycle and 56mg/m2 day eight and day fifteen of that first cycle and for all the subsequent cycles day one, eight and fifteen the 56mg/m2 is the dose of carfilzomib and that could be partnered with lenalidomide and dexamethasone.

The study was a phase Ib study so therefore the main focus is to look at safety and feasibility. The safety data shows that there were very few grade 3 or higher adverse events. There were no patients on this study that had congestive heart failure. A lot of people talk about cardiac issues with carfilzomib and there is a signal for that but importantly this is in the setting of newly diagnosed patients so they don’t have a lot of problems and also, as part of the inclusion criteria, patients had to undergo an echocardiogram of the heart and the ejection fraction had to be 40% or higher. So that’s very important clinically – if you look at newly diagnosed patients and you do an echocardiogram you can sort out those patients who should not be treated with carfilzomib. Then if you do it right in this way you also don’t run into a lot of problems with congestive heart failure.

When it comes to the efficacy for response that was not the primary endpoint because it’s a phase Ib study. There was less information and it also comes back to the study design. The study allowed for up to 18 cycles of this regimen but it did not mandate a certain number for every patient. Patients could get up to 18 cycles. Patients were also allowed to get whatever number of cycles the doctor and the patient agreed to and then they could go on to transplantation. If they did that they could stop that or they could actually go back and get residual cycles up to a total of 18. So that makes it a little bit more complex when you’re trying to understand the depth of the response if you include all the patients because some patients did go to transplant and some did not. So out of the total sample size of 33 patients if you look at the overall response at four cycles I believe it was around 70% or so of the patients that had a very good partial response or better in that range. But if you take out those patients who did go to transplantation and only focus on patients who continued on therapy without transplant, the number was slightly less than 20 then out of the 33, then you see that the complete response rate was more than 50%. So these are very good results, obviously.

So you should not do a formal comparison from one study to the other, you should only do that in a randomised study compare the arms, but we do all the time and we look at different studies and we talk about it so I’m going to do that too. So if I look at the published phase II studies with the twice a week 36mg/m2 dosing with carfilzomib and with lenalidomide dexamethasone, these results look very, very similar. So my overall conclusion is that the once a week 20mg/m2 56mg/m2 dosing, as I just outlined, is a very safe regimen, is very feasible to give and it also seems to have the same efficacy as you would see in the twice a week 36mg/m2 dosing schedule. I think it’s a great option prescribing carfilzomib once a week at this dosing.