GRIFFIN Trial Overview

EP: 1.MAIA Trial Overview

EP: 2.Quality of Life in Multiple Myeloma Patients

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EP: 3.GRIFFIN Trial Overview

EP: 4.GEM-CESAR Trial Overview

EP: 5.MagnetisMM-1 Trial Overview

Saad Usmani, MD, MBA, FACP: My colleague [Rebecca] Silbermann, [Md, MMS,] if I remember correctly, presented these data as an oral abstract at ASH [American Society of Hematology annual meeting]. GRIFFIN was a randomized phase 2 study in transplant-eligible patients, so a different patient population than in the MAIA trial we just talked about. The GRIFFIN trial compared the standard of care approach of treating patients with RVd [lenalidomide, bortezomib, dexamethasone]

for induction, and there was a post-transplant consolidation with RVd, followed by lenalidomide as maintenance treatment. To that standard of care arm, daratumumab was added in the experimental arm. So [daratumumab]-RVd was utilized as induction, followed by daratumumab-RVd as consolidation for 2 cycles post-transplantation, and then daratumumab, lenalidomide was used as maintenance treatment. Patient-reported outcomes [PROs] were examined as part of this study. The GRIFFIN trial was reported on a little over 2 years ago, showing that the depth of response in terms of stringent CR [complete response] rates, which was the primary end point for the study, was superior in the daratumumab-containing arm.

This study helped in informing 2 randomized phase 3 trials, the CEPHEUS and PERSEUS studies, which are hopefully going to be read out in the next year or so. This particular analysis, again, looked at the patient-reported outcomes that were assessed at baseline, as well as subsequently after each cycle of induction and consolidation post-transplantation, and Q6 [every 6] months during the maintenance period. The EORTC QLQ-C30 [European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire] was utilized again, and there was a myeloma-specific MY20 [multiple myeloma 20-item questionnaire]that was utilized on top of the QLQ-C30 scale. The objective was again to see if there are going to be any differences in the quality of life between these 2 arms.

What stuck out to me was looking at the global health status, the physical and emotional functioning over time, all of those measures improved more significantly for the 4-drug induction, consolidation, followed by a 2-drug maintenance arm compared to the standard of care arm on the study. It improved over time when you looked specifically at pain and fatigue symptoms. I think the most notable message I found was the improvement in the pain symptoms, and that speaks more so for better disease control than anything else. The median time to worsening of the global health care score was much longer in the daratumumab-containing arm, and that represents perhaps the longer disease control that was observed on that arm of the study. This data set was used as an exploratory end point as part of GRIFFIN. But it adds to the growing evidence that we need to incorporate these health-related quality of life measures as important secondary end points in our clinical trials, especially the large, randomized phase 3 studies incorporating newer therapies that will change the standard of care. With patients living longer, again, it’s very important to make sure there is no deterioration or adverse effect on the quality of life measures.

My take on this is based on some of the discussions we recently had at the International Myeloma Society/FDA combined workshop on myeloma that was held before ASH, where all of these issues were discussed, including the potential regulatory use of the health-related quality of life measures and PROs. The key takeaway from those interactions was when you’re comparing 2 very effective regimens, when you’re trying to bring a novel therapy into the schema of myeloma treatment, and comparing it to the standard of care, you want to make sure that the health-related quality of life measures are not poorer in the experimental arm. So while you are trying to prove efficacy, make sure that the quality of life is not impacted adversely for patients, and I think that’s the key message.

The way we can utilize these data is by making sure that the quality of life at the very least is the same, if not better. If it’s better, that’s wonderful, if the experimental arm is showing excellent response rates, PFS [progression-free survival] looks wonderful, and we’re extending overall survival in those patients. But that should not be at the expense of adverse quality of life in the experimental arm. More data coming out demonstrating that would be helpful. If the survival outcomes and responses appear to be somewhat similar, and the quality of life for that experimental therapy is poorer than the standard of care, then I think we need to question the utility of that new therapy.

Transcript edited for clarity.