Weekly 20/56 mg/m² carfilzomib, lenalidomide and dexamethasone until progression in early relapsed refractory multiple myeloma

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Published: 6 Jun 2019
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Prof Xavier Leleu - Centre Hospitalier Universitaire de Lille, Lille, France

Prof Xavier Leleu talks to ecancer at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting about the use of carfilzomib, lenalidomide and dexamethasone in the relapsed setting.

He discusses why this weekly treatment regimen is important and more practical instead of being administered twice a week.

He also mentions the advantages associated with this type of treatment, which include improved quality of life and progression-free survival.

Prof Leleu mentions the new phase III trial, AERO-2 which will examine the administration of carfilzomib at 56mg/m² once a week compared to carfilzomib at 27mg/m².

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.

The abstract presented by Cecile Gruchet is also on carfilzomib but slightly different. So when carfilzomib Revlimid dexamethasone in the relapsed setting, early relapsed setting, first relapse second line or second relapse third line, when it was launched in France, that was years ago, it was launched based on the ASPIRE design where carfilzomib is given at 27, 1, 2, 8, 9, 15, 16 of 28 day cycles. But the thing is that in the area where I work it’s very much not easy and not convenient to the patients because most of the patients I take care of in the area where I live, which is not a lost place in France but it’s not Paris, patients have to commute a lot to come to hospital, approximately 1½ hours median. Some of the patients it takes three hours to come to hospital. So we had to reinvent the way of giving carfilzomib because it was hardly feasible to have the patient come forth and back twice a week, three weeks in a row out of four weeks. It would be extremely expensive, patients would complain from fatigue, it would be really not quality of life driven.

So since 27x2 makes 54 and we had experience with 56 in ENDEAVOR, we knew that we could probably give 56 once a week instead of 27 twice a week, still combined to Rev/dex. So we performed a series of approximately 30 patients, the proof of concept that you can give carfilzomib at 56 once a week, 1, 8, 15, instead of 27, 1, 2, 8, 9, 15, 16 out of 28 days. We demonstrated, one, that we have approximately the same results as ASPIRE, as good; two, quality of life convenience is enormously improved; three, instead of stopping at 18 months the carfilzomib like ASPIRE we were able to continue beyond 18 months and the patients who have not progressed still on carfilzomib are actually doing extremely well. Plus, four, at the time the patients get a bit sick of 1, 8, 15 once a week you can put them into a maintenance profile, 1, 15 or 1, 21, still out of 28 days. This helps continuing the proteasome inhibitor for a much longer period of time and gaining probably time free of relapse for these patients that are really benefitting and responding from the treatment while in any other situation and clinical trials that have developed with carfilzomib at some point you stop the carfilzomib. So we have the feeling that this was a real breakthrough in the way of using carfilzomib and make it more future, for tomorrow.

We were able to convince Amgen that this was really a great change, a great move for their drug and they have actually launched a couple of days ago a phase III trial which is called A.R.R.O.W. 2 where they are going to compare their K/Rev/dex approved with K 27 1, 2, 8, 9, 15, 16 to K/Rev/dex where K is given at 56 once a week. So we are very happy because a small study conducted in a small place in the middle of nowhere in France was able to drive a major change for the company which is not very often that we can have such a success.

So this presentation from Dr Cecile Gruchet was an update focussing on elderly patients and focussing on the patients that were able to go beyond 30 months, meaning a much improved PFS compared to ASPIRE.