The GRIFFIN Study is a post-hoc analysis of sustained MRD negative status in the griffin study which treated patients with newly diagnosed multiple myeloma who are transplant eligible with their tumor map Lenalidomide and dexamethasone as the study arm as part of their induction consolidation after transplant and with Daratumumab (DARA) + lenalidomide as maintenance compared to the control arm which was RVd as part of their induction post-transplant consolidation and then maintenance and after all the patients completed two years of maintenance with a median follow-up of 38 years we evaluated sustained MRD negativity lasting 6 months or higher and 12 months or higher between both groups the baseline characteristics between both populations was similar the number of patients were 207 and when we look at the two groups the control arm and the study arm for MRD a negative status of six to six months or higher at ten to the minus five we do see that there are improved rates of sustained MRD negative status in the study arm the arm that contained diagonal map compared to the control arm and this applies to all of the subgroups of interest which include age uh minus 65 or greater than 65 stage and if they achieve the complete remission or not or a stringent complete remission this also applies as a tendency in high-risk disease although there's some variability there because this study was not powered enough to con to evaluate this answer we do see a tendency of improvement in the control arm sorry
We do tend to see an improvement in the steady arm compared to the control arm and high-risk disease, which includes 17p deletion translocation 414 and translocation 1416. as well as the revised piracy disease which includes additionally one q gain and translocation 1420. when we look at 10 to the minus 6 we also see a tendency towards improvement or better MRD negativity that is sustained in the study arm at six months or higher although the amount of patients that were evaluated ten to the minus six was very small similarly when we look at sustained MRD negative status for 12 months or higher we do see that the dairy tumor map RVd arm is higher compared to the control arm which was just RVd alone amongst all subgroups uh most star groups of the higher sensitivity threshold at 10 to the minus 6 had improved rates of sustained MRD negative status lasting 12 months or higher except for the revised higher high cytogenetic risk which included the 1q gain and the translocation 1420 and i also want to point out that this study had very few patients of high-risk disease so it is really not powered to represent or answer the question of whether high-risk disease patients did benefit from the dairy treatment map versus the control arm when we look at PFS by sustaining MRD negativity the medium PFS by durable MRD negativity at the 10 to the minus 5 and 10 to the minus 6 threshold that lasted 6 months or higher or 12 months or higher was not reached for any group it was though consistently better in the dara RVd group versus the RVd group with among the patients who did achieve durable MRD negativity at 10 to the minus 5. the PFS was also improved for all groups who reached durable MRD negativity lasting 6 months or higher or 12 months or higher compared with patients who did not reach durable MRD negativity emphasizing the importance of achieving the surrogate endpoint so among all the patients with sustainable dna activity only one dara rbd patient had disease progression and one RVd a patient in the control arm died of causes unknown both patients had high risk cytogenetics so the take-home message of this study is that after two years of maintenance therapy the rates of sustaining MRT net activity at 10 to the minus 5 less than 6 months or higher or 12 months or higher was improved for the daratumumab RVd arm which was the study arm compared to the control arm which was just RVd this was in relevant subgroups including isa stage three high result genetics and revised high-risk cytogenetics and these trends were generally similar when measured at the higher MRD sensitivity threshold of 10 to the minus six although some variability was seen in parts due to the small patient number that we had that had tests at 10 to the minus six another takeaway point is that sustained MRD negativity lasted six months or higher or 12 months or higher was associated with improved PFS for all intention to treat patients underlying the importance of achieving the surrogate endpoint and these data are consistent with previous reports that daira based therapies for newly diagnosed myeloma are associated with higher negativity uh MRD status lasting six months or higher or 12 months or higher and it's a prognostic factor which can translate to improved PFS.
Common Questions From Your Colleagues?
There are a couple of questions that we commonly get asked by other colleagues the first one is is quad the new normal and it's quad now the standard of care and is four better than three i will say that with all of the data that we are having at the moment using a quad that includes stereotumor map seems to be having much better uh depth of response and durability of the response compared to the triplets and into standard therapy we currently have a phase three ongoing study that's going to help answer uh better this question but in my opinion i do believe that that quads are better than three at this point and the dara should be added as a backbone as part of induction therapy as well as relapse therapy another question i get asked a lot is do we have data for high-risk disease patients and does their benefit patients with high-risk disease based on the griffin study and unfortunately this study had is not powered to answer that question but we do have a phase three study ongoing that will hopefully give us the information to answer the question of whether adding daira does benefit patients with high-risk disease another question we kept getting asked frequently from our colleagues is does the addition of dairy tumor map increase the risk of these patients in terms of side effects or other complications and adding daratumumab to a triplet regimen does not really increase significantly the side effects and toxicities right now during the pandemic it does increase the potential risk of having complications from covid so that is something that we do need to keep in mind during this pandemic but if patients are vaccinated and are monitored closely maintain proper protections with face masks and distancing themselves from anybody who might be a risk of contact this could potentially be improved but definitely this is it does not add a lot of toxicities to the triplet regimen it is a safe agent and the rates of response and the depth of the response definitely seems to be worth the increased slight side effects that we're seeing by doing quads.
Will This Affect Clinicians Today?
I believe this data demonstrates that adding data to a map to RVd as part of induction in transplant-eligible patients does improve the depth of the response and can translate to a longer PFS and especially if they have sustained MRT negative status, which we're seeing a higher rate of MRT sustained MRD status in griffin study and those who did receive their tumor map is this now the standard of care it's still not FDA approved, but I do believe that a lot of people are adopting it I am an early adopter as well, so hopefully this data is going to make colleagues more comfortable adapting quads as part of their induction therapy and this data also adds to the existing data in transplant-ineligible patients and other studies for newly diagnosed myeloma patients that were down in Europe incorporating their tumor map as part of the induction showing that there is a benefit in terms of the depth of response and the duration of the response.
What Are The Next Steps?
The next step for this research is um twofold one is uh to collect the data and finish the phase three study that will hopefully give us answers as to whether dara does benefit people who have high-risk disease and if it is making an impact and that are hard to treat a population and also to get FDA approval so this can become standard of care in the united states and hopefully as well across the world.
I do want to state that the data from this study does show that adding daratumumab to standard of care, in this case, RVd as part of the induction consolidation and during with land maintenance in transport eligible patients is definitely increasing the depth of the response it's increasing the degree of sustained MRD negativity in these patients, and it's also prolonging the PFS which is our first shot is always our best shot when it comes to myeloma we don't have the ability to cure the majority of the patients at the moment, but if we have patients stay in remission for a longer period of time it might give us an opportunity for a new therapy or a new clinical trial to open so that patients can be treated with that at the time of relapse so even though these agents might not be curative at the moment the way we're using them the depth of the response and the duration of the response definitely do matter.
GRIFFIN Study Details:
The goal of this study is to see if adding daratumumab to lenalidomide-bortezomib-dexamethasone (RVd) increases the proportion of participants who achieve stringent complete response (sCR), as defined by the International Myeloma Working Group (IMWG) criteria, by the time of completion of post-ASCT consolidation treatment, when compared to RVd alone.