February 22, 2019
First Report Managed Care: Hello everybody. With us today is Dr Ravi Vij, MD, MBA, from Washington University School of Medicine in St Louis.
Dr Vij presented at the ASH Annual Meeting and Exposition on patients with relapsed or refractory multiple myeloma after daratumumab treatment. He presented on real-world findings from a pooled data analysis, PREAMBLE, and the McKesson electronic medical record database. This presentation was reflected in abstract 3284 and Dr Vij has come on today to speak with us more in depth about this abstract.
So, thank you for joining us today, Dr Vij.
Your study evaluated treatment sequences among patients with relapsed or refractory multiple myeloma after failure of daratumumab-based therapy. Why did you determine this aim was an important one and what is the unmet need in regard to relapsed or refractory multiple myeloma?
Dr Vij: We have chosen to address the issue of treatment for patients who have been treated with daratumumab because that is one of the major unmet medical needs in the current population of myeloma patients who are refractory to earlier lines of treatment, especially patients who are what we call penta-refractory which are those that have progressed not only on daratumumab, but also on prior proteasome inhibitors and immunomodulatory drugs. That population is one that we certainly have options that we can turn to using old chemotherapy combinations, but there are no FDA-approved treatments and those patients are also challenging to treat because of their performance status and also their matter reserve. So, trying to figure out what is best to do for this population is an important question.
First Report Managed Care: When designing your study, what databases or studies did you pull from for your population and why were these chosen?
Dr Vij: So, the database that we have been presenting at numerous conferences using is the PREAMBLE database, which is a registry that is run by Bristol-Myers Squibb trying to get a real-world view of patients both in the front-line treatment and in relapse/refractory lines of treatment. Patients are followed longitudinally and a series of questionnaires are filled in by the participating sites.
The other database that we are using for the presentation at the ASH 2018 meeting is McKesson EMR, which is a database that is being combined with the database from PREAMBLE for the first time in the PREAMBLE database presentations.
First Report Managed Care: Moving through the results of your study, what did you find were the most commonly used daratumumab-based regimens among your population and were these regimens the expected ones or were you a bit surprised?
Dr Vij: I think that the daratumumab-based regimens were mainly those combining daratumumab with immunomodulator drugs and with proteasome inhibitors, so I do not think there is much surprise on the choice of the combination regimens. Among the patients, the most commonly used immunomodulatory drug combination was that with pomalidomide. That again is not surprising, given the fact that lenalidomide gets used in earlier lines of treatment and so, trying to change the partner with daratumumab makes more logical sense. And especially in the earlier phase of adoption of daratumumab, it was often given in much later lines of treatment. The use of daratumumab-based combinations with Velcade and lenalidomide are certainly becoming more popular now even in second-line, but the data we captured is perhaps still weighted a lot towards the use of daratumumab in later lines of therapy when it is initially used, initially started.
The proteasome inhibitor form the combination with daratumumab in about one-fourth of patients. There were a few patients that got it either as single-agent or in combination with steroids and very few that got it with anything else.
First Report Managed Care: Were there any other surprises or unexpected findings from your study, perhaps in relation to elotuzumab or any other just landmark findings from this particular study you wanted to discuss?
Dr Vij: I think that what we found was great heterogeneity as expected in the patterns of care because there is, as I said, no FDA-approved regimen for daratumumab failures. We saw patients being treated with a variety of chemotherapy-based regimens using the immunomodulatory drug combinations or the proteasome inhibitor combinations with daratumumab in more than one line of therapy.
And then, obviously, we did see some use of elotuzumab in this population as well. The elotuzumab-based regimens were mainly in combination with lenalidomide.
What came as somewhat of a surprise to me was the fact that in addition to 20% of patients actually being given elotuzumab-based regimens, the patients who got the elotuzumab-based regimens had a fairly similar chance of response compared to any other modality of therapy that was tried. Also, the durability of the treatment success in excess of three months was fairly similar to that what we saw with other approaches.
Most of the data with elotuzumab, at least during the period that this study covered, was in earlier lines of treatment and some physicians have been somewhat reluctant to adopt elotuzumab in daratumumab failures given the lack of any data from clinical trials and also until this time, lack of much in the way of real-world registry data.
So, I think that this presentation for the first time brings forth elotuzumab, especially in the future with pomalidomide and dexamethasone, as being a viable option for patients. Certainly, one needs to keep in mind the caveats of this being a real-world registry study and not a properly conducted clinical trial, so there may have been some selection bias in patients who got the various regimens. But I think that as we have seen, that elotuzumab with pomalidomide and dexamethasone in a phase 2 randomized study also at the European Hematology Association Society meeting in June 2018 showed a very impressive result that it would become I think a more popular regimen going forward for patients who have progressed on a daratumumab-based regimen.
As far as the data goes, in terms of time to next treatment I would say that the 151 days as duration of therapy is what one knows for the treatment regimen employing elotuzumab. It was roughly about 117 days for combinations of proteasome inhibitors immunomodulatory drugs which was the second best among the real-world registry numbers. And then, daratumumab re-treatment regimens came in at 94 days for duration of subsequent therapy.
So, I think that again, one has to preface this with the caveat that this is not any randomized clinical trial. There is a lot of selection bias often in these real-world populations. But it was at least gratifying that the duration of treatment on these subsequent regimens with elotuzumab was comparable if not superior to some of the other regimens that were employed in the real world.
First Report Managed Care: How can the results of your study benefit the myeloma community and what audience do you hope to target with your presentation?
Dr Vij: I think that this ASH meeting, this presentation and in conjunction with quite a few others, are trying to address the issue of what to do for patients who have progressed on daratumumab. All of these are at this time real-world studies either multi-institution, single institution, or registry studies like the one that I have just been alluding to. All these tell us that there is roughly a 30% chance of response to the subsequent regimen after progression on daratumumab-based regimens and the median duration of response usually is anywhere from 2-4 months. But patients can go on to successive treatment in multiple lines of therapy, each with somewhat lower response rates and lower durability, but can often get a year or more going from one treatment to the other, which is often a boon for patients and often will allow them to sometimes transition on to therapies that are coming down the pike that may offer them yet more benefit for the future like CAR-T cells might, and antibody drug conjugates among others.
First Report Managed Care: Are there any other important points or parting messages that you would like to discuss at this time?
Dr Vij: This was a very large population-based study of over 1000 patients that is being reported, which is the largest experience to date. From two different databases, to get over 1000 patients that have seen daratumumab is the first to date in terms of any report.
I would also say that the data comes from both the United States and Europe. So, it has implications that are beyond just the United States, so that is another thing that needs to be kept in perspective as well.
I think these kinds of real-world databases are going to be very informative going forward in telling us what treatments to use and answer a lot of other issues around the cost economics and other aspects of care that we do not have answers to today.