Improving Management of Relapsed/Refractory Multiple Myeloma - Episode 4

Looking at GRIFFIN Trial Data


Thomas Martin, MD: There are a couple of other interesting presentations at the virtual ASCO [the American Society of Clinical Oncology annual meeting]. I’m going to go back to ASH [the American Society of Hematology annual meeting] of 2019 and talk a little bit about the GRIFFIN study. Peter Voorhees, MD, presented the GRIFFIN study at ASH 2019, and we’ve all been waiting for this.

Yvonne Efebera, MD: It’s now published too.

Thomas Martin, MD: Yes, it discusses adding daratumumab to VRd [bortezomib, lenalidomide, dexamethasone]. It was a phase 2 randomized study, just over 200 patients involved. Half the patients were randomized to VRd, 4 cycles, a single autologous transplant, VRd, 2 cycles, consolidation, and then REV [Revlimid] maintenance. The other half had DARA [daratumumab] added in, so it was DARA/VRd for 4 cycles, single autologous transplant, DARA/VRd for 2 cycles, and then DARA/R [Revlimid] as maintenance-based therapy where the DARA is given. Initially it was given every 8 weeks, and then they changed it so a patient could get it every 4 weeks or every 8 weeks, so we’ll see if there’s a difference there. They gave it for 2 years. And then after that patients could continue on lenalidomide maintenance.

The primary end point of the study was stringent complete remission. At ASH, the presentation was to show that the study met its primary end point where the stringent complete remission basically was 42.4% in the DARA/VRd arm versus 32% in the VRd arm. And then the overall response rate post-consolidation was actually 99% in the DARA/VRd. We put patients on the trial at UCSF [University of California, San Francisco]. We had about 10 patients on the trial, and we were all very impressed with the rapid reduction of the tumor burden from DARA/VRd as induction, and then their post-transplant had good, deep responses.

The 24 month PFS [progression-free survival] was 96% in DARA/VRd and it was about 90% in VRd. There’s no statistical difference in that just yet. The thought is that these patients are going to be in remission. The PFS may end up being 6 or 7 years. That is an amazing thing, that if we put a patient on the trial today or that therapy, they’re going to be in remission for 6 to 7 years. When they come out, and we’ll talk about relapse later, when they come out of remission and go into relapse, who knows what we’re going to give them 6 or 7 years from now. It’s going to be a whole new playing field, which is really kind of fun. And there was a higher number of MRD [minimal residual disease]-negative patients in the VRd.

The other abstracts from ASH I’ll mention briefly were some DARA/KRd [carfilzomib, lenalidomide, dexamethasone] abstracts. In this one it was the weekly carfilzomib. One was from Dr. Ola Landgren, MD, PhD, who did DARA/KRd. He did a 2-cohort study. One was weekly carfilzomib and the other was twice weekly carfilzomib. Between the 2—the weekly was 56 mg/m2, the twice weekly was 36 mg/m2—they did 8 cycles of this therapy, standard lenalidomide at 25 mg and dexamethasone, 40 mg weekly. The efficacy and the safety were similar between the weekly and the twice weekly, which was quite interesting and great. There were many fewer doses, the average being 20-some doses of carfilzomib in the weekly dosing, and over 50 doses of carfilzomib. So just in convenience, it was much better if you did weekly dosing.

And the goal of the study was interesting. It was to try to induce an MRD negativity rate of over 60%. And in fact, what Ola described is in 18 patients for whom they did MRD testing, of the weekly carfilzomib at 56 mg/m2, day 1, 8, and 15, with 25 mg of LEN [lenalidomide] and 40 mg of DEX [dexamethasone], they had 83%, or 15 out of 18, achieved MRD negativity. Pretty amazing actually, quite an amazing regimen.

The other interesting trial was the MASTER trial, which was presented by Luciano Costas MD, PhD,, who also used DARA/KRd and the K [carfilzomib] was 56 mg/m2 weekly. They gave 4 cycles of induction, and then they checked MRD. Then they did a single autologous transplant, and then they checked MRD. Then they did 4 more cycles of KRd/DARA and checked MRD, and another 4 cycles of KRD/DARA. But the goal with the checking of the MRD was once patients had 2 consecutive MRD-negative results, they could come off therapy. They were able to stop therapy.

Now, he just presented the initial data showing basically after 4 cycles of DARA/KRd, the VGPR [very good partial response] or better rate was over 90%. And then after consolidation, more than 80% of patients were MRD-negative. It was a pretty potent regimen. In terms of how many were able to come off therapy and be able to stay off therapy for a long period, again, trying to give intensive therapy over a short period, we’ll have to see how that works out. I suspect he’ll present it again virtually at ASH of this year. We’ll see.

Transcript Edited for Clarity