The study is evaluating daratumumab plus lenalidomide, bortezomib, and dexamethasone in autologous stem cell transplant eligible patients newly diagnosed with multiple myeloma.
Peter Voorhees, MD, myeloma physician at the Levine Cancer Institute, discussed results from the ongoing GRIFFIN study, which evaluated daratumumab (Darzalex) plus lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (Ozurdex), also known as RVd, in autologous stem cell transplant eligible patients newly diagnosed with multiple myeloma.
Results from the randomized phase II study were presented at the 61st American Society of Hematology (ASH) Annual Meeting & Exposition, held in Orlando, Florida, from December 7-10, 2019.
Sure, so the primary endpoint of the study was stringent complete response by the end of consolidation after transplant. So, the way that we designed the study is that patients received RVd for 4 three-week cycles. They then underwent stem cell transplant, 2 cycles of post-transplant consolidation, each cycle consisting of 3 weeks, and then they went on to maintenance therapy with lenalidomide. The daratumumab arm got weekly daratumumab during induction therapy. They received daratumumab on day 1 of each of the consolidation cycles and then received daratumumab once every 4 weeks in maintenance for up to 2 years, and patients were encouraged to stay on lenalidomide beyond that, until disease progression or emergence of unacceptable side effects.
So, we know that just with RVd alone in the transplant setting, the expected median progression-free survival is 50 months, and that’s when lenalidomide maintenance is only used for 1 year. So, we expect it to be even longer for those patients to stay on lenalidomide maintenance longer. So, there’s really a compelling need for surrogate endpoints that read out earlier that are predictive of longitudinal outcomes of progression-free and overall survivals. So, in that regard we chose stringent complete response by the end of consolidation. And what we presented at IMW in Boston, back in September, was that we had met our initial, you know, primary endpoint. So, the patients on the daratumumab arm had a stringent complete response rate of 42.4% by the end of consolidation therapy, in contrast to 32%, you know, in the control arm.
With longer follow-ups, so at that time, median follow-up was 13.5 months. Here at ASH, you know, we have median follow-up of 22.1 months. And I’m happy to report that depth of response continues to improve in both arms, but clearly continues to favor the daratumumab arm, and even more so than it did before. So, by the end of this particular data cut, the stringent complete response rate was 63% in the (daratumumab) arm and it was 45% in the control arm, and that was highly statistically significant. And we also looked at MRD and we specifically looked at MRD negativity at a sensitivity level of 10-5 using next generation sequencing. And what we’ll report here at ASH is that the MRD negative rate in the daratumumab arm is approximately 50% in contrast to 20% for those in the control arm, so clearly establishing greater depth of response for those patients receiving daratumumab with their RVd.
International Myeloma Foundation. Depth of Response to Daratumumab (DARA), Lenalidomide, Bortezomib, and Dexamethasone (RVd) Improves over Time in Patients (pts) with Transplant Eligible Newly Diagnosed Multiple Myeloma (NDMM): Griffin Study Update. International Myeloma Foundation website. Published December 12, 2019. myeloma.org/ash-2019/depth-response-daratumumab-lenalidomide-bortezomib-dexamethasone-improves-over-time. Accessed February 11, 2020.