Multiple Myeloma and Stem Cell Transplantation

An expert in the management of multiple myeloma discusses new data released from the GRIFFIN trial as well as real-world evidence regarding frontline autologous stem cell transplantation.

Joshua Richter, MD: The GRIFFIN study [NCT02874742] is the United States’ answer to the CASSIOPEIA study [NCT02541383]. Outside of the United States, the standard for upfront transplant-eligible patients can be regimens such as bortezomib/thalidomide/dexamethasone [VTd]. The CASSIOPEIA trial sought to augment that and compared the VTd [bortezomib, thalidomide, dexamethasone] backbone to daratumumab/VTd [bortezomib, thalidomide, dexamethasone]. In the United States, bortezomib/lenalidomide/dexamethasone [VRd] is our standard, and the GRIFFIN study compared that with daratumumab/VRd [bortezomib, lenalidomide, dexamethasone], the quadruplet. These patients are allowed to go on to stem cell transplant. One of the things that we’re seeing from the recent update in the GRIFFIN study is the very high rates of minimal residual disease [MRD] negativity at the rate of not only 10-5 but also 10-6.

Although the response rates are not much different between VRd [bortezomib, lenalidomide, dexamethasone] and daratumumab/VRd [bortezomib, lenalidomide, dexamethasone], we’ve recognized that the depths of response are overall deeper with the quadruplet. What does this mean? Essentially, we’ve now documented that the deeper your remission is at every stage of the game correlates to more durable and better outcomes. Those who achieve a PR [partial response] will do better than the MR [minimal response], VGPR [very good partial response] will do better, CR [complete response] better, and MRD even better than that.

One of the other things that GRIFFIN is calling into question is the role of stem cell transplant. There were some data recently presented from the IFM/DFCI 2009 study [NCT03679351] showing that patients who achieve MRD negativity at the end of induction do not necessarily benefit from the stem cell transplant. One of the things that GRIFFIN may do is show that if we can get so many patients into these really deep remissions, the MRD negativity, we may not necessarily need to transplant these patients anymore. We’re really looking forward to the final readout of this study, but there are very encouraging data so far.

Patients are really excited at some level to finally get on the other side of their transplant, and many of them hope that they’d be done with all of their treatment. There have been many studies throughout the years looking at maintenance therapies after transplant. The majority focus on things such as lenalidomide and bortezomib, but there are a few others as well. In the real world, we recognize that many patients do receive maintenance therapy after transplant, but there’s a lot of variation from institution to institution and practice to practice. What we find from the real-world data is that people who receive some type of maintenance, whatever it is, not only have improved progression-free survival but a trend toward overall survival.

Now that we have multiple ways of approaching the maintenance strategy, either with proteasome inhibitors like bortezomib, or immunomodulatory drugs like Revlimid, we have further follow-up data to suggest the benefit of maintenance therapy. We always question when we see data from clinical trials as to whether that’s applicable to the patient in front of us in the clinic.

I think one of the great things about the real-world data presented was showing that the average patient we see out in the community does benefit from continued therapy, despite the fact that they’re in remission. To me, this really contextualizes the idea that we see patients month in and month out post-transplant. They don’t have measurable disease, but we need to continue to keep them on some version of maintenance therapy, adjusted for not only risk but adverse effect profile. With a number of better tolerated drugs nowadays we have a lot of options. It still leaves lenalidomide/Revlimid as the standard, but it’s really important to incorporate some degree of maintenance therapy post-autograft.

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