Daratumumab in combination with carfilzomib and dexamethasone for relapsed multiple myeloma

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Published: 4 Jun 2018
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Dr Ajai Chari - Mount Sinai Hospital, New York, USA

Dr Chari speaks with ecancer at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting about the MMY1001 study, looking at daratumumab in combination with carfilzomib and dexamethasone in lenalidomide-refractory patients with relapsed multiple myeloma.

Dr Chari also spoke with ecancer about subcutaneous daratumumab, here.

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 MMY1001 study is basically the addition of daratumumab to various backbone regimens in myeloma and this particular cohort is the addition of daratumumab to carfilzomib and dexamethasone, the so-called DKD regimen.

In this study the safety results have already been presented previously and show really that the addition of daratumumab doesn’t really add much to the toxicity profile that you would expect.

In terms of the efficacy, what is updated here at this year’s ASCO meeting is the subgroup of lenalidomide refractory patients.

The reason that’s important is that there have been a lot of phase III studies that have been published recently in high impact journals where novel agent triplet based regimens are compared to lenalidomide and dexamethasone backbone regimens.

The problem is that the vast majority of patients in the US are now getting lenalidomide maintenance because we know that that led to an increased OS benefit and therefore there’s an increasing use of lenalidomide which then would make all of these people ineligible for the phase III studies that we just covered

So the lenalidomide refractory cohort here was 50 patients of the entire group of 85 patients of DKD.

In the lenalidomide refractory cohort the response rate was no different than the overall cohort, about 80%, including in that CR, stringent CRs, and even one patient who had MRD negativity although that was not a primary endpoint of the study.

The more important and interesting result is the progression free survival was 14 months which, in this particular population for lenalidomide refractory, is very encouraging.

We should use caution when doing cross-study comparisons but to put it in the context of other studies lenalidomide refractory outcomes for pomalidomide-dexamethasone was approximately 4 months, admittedly with a more heavily pre-treated population, but with other regimens in this one to three lines of therapy space with lenalidomide refractory the PFS have ranged from 8-9 months.

So this 14 months is encouraging and it will be interesting to see the results of the randomised phase III study of carfilzomib, dexamethasone plus/minus daratumumab which is already ongoing and results will be very important for drug approval.

The other important message from the 1001 study with this DKD cohort is the ability to give daratumumab as a split dose.

Because up until now one of the main limitations of giving daratumumab in the community has been the long first dose infusion time, median 7 hours.

The infusion related reactions in that first dose can be approximately 40-50%.

Here, daratumumab was given as a split dose in 75 patients and the median infusion time was approximately 4 hours each day.

The infusion related reactions were only about 37% in the first dose and less than 3-4% in the second dose.

So this ability to give daratumumab over two days is really going to be an important advancement for community doctors and patients for convenience.