Choosing the Appropriate Induction Regimen in Transplant-Eligible NDMM
Surbhi Sidana, MD, and Caitlin Costello, MD, introduce the updated evidence regarding induction regimens for patients with transplant-eligible NDMM and how to select the appropriate induction regimen in this population.
Surbhi Sidana, MD: Hello, and welcome to this CancerNetwork®️ Around the Practice program, titled "Recent Advances in Multiple Myeloma: Updates from the IMS 2022 Meeting and Beyond." I'm your host, Dr Surbhi Sidana. I'm an Assistant Professor of Medicine at Stanford University, and I also lead the Myeloma Cellular Immunotherapy program at Stanford. I'm joined by a great panel of experts here, and I would like to invite my esteemed panelists to introduce themselves. Dr Larry Anderson?
Larry Anderson, MD: Hi, I'm Dr Larry Anderson. I'm a myeloma and cell-therapy specialist at UT [University of Texas] Southwestern Medical Center in Dallas, Texas.
Surbhi Sidana, MD: Dr Caitlin Costello?
Caitlin Costello, MD: Hello, my name is Dr Caitlin Costello. I'm an Associate Clinical Professor of Medicine at the University of California, San Diego in the Division of Blood and Marrow Transplant.
Surbhi Sidana, MD: Dr Andrew Cowan?
Andrew Cowan, MD: Hi, I'm Dr Andrew Cowan. I am an Associate Professor of Medicine at the University of Washington, and I also have joint affiliation with Fred Hutch [Fred Hutchinson Cancer Research Center].
Surbhi Sidana, MD: Dr Rebecca Silbermann?
Rebecca Silbermann, MD: Hi, I'm Dr Rebecca Silbermann. I'm an Associate Professor of Medicine at Oregon Health and Science University in Portland, Oregon, and I lead our myeloma program.
Surbhi Sidana, MD: Thank you all for joining me today for this exciting discussion. We are hoping to discuss abstracts presented at IMS 2022 [International Myeloma Society Annual Meeting], as well as data that was presented at the recent ASH [American Society of Hematology] and ASCO [American Society of Clinical Oncology] meetings and see how we can apply these advances in multiple myeloma into our daily practice. Let's begin.
For the first section, let's discuss the evolving frequent landscape in patients who have transplant-eligible multiple myeloma. When we meet transplant-eligible patients, we meet patients who have a good fitness status and can potentially undergo transplant. It's a very controversial issue whether everyone should undergo a transplant, and I'm hoping to talk to my panel members about that today. But before we get into that, when someone is diagnosed with multiple myeloma in 2022, they either receive a triplet regimen or a quadruplet regimen; there are some transplant-ineligible patients who receive a doublet regimen, and we'll come to that later. The most common triplet regiments we have today are VRd or KRd, which is bortezomib, lenalidomide, and dexamethasone, or carfilzomib, lenalidomide, and dexamethasone. There's a lot of data for these regimens, making these 1 of the standards of care regimens that we have today. Sometimes, patients with renal dysfunction also get VCd, which is bortezomib, cyclophosphamide, and dexamethasone. But what we see more over the last couple of years is that data for quadruplet therapy looks really promising, which includes daratumumab in addition to these regimens. Daratumumab-VRd, daratumumab-KRd, daratumumab-based thalidomide-based regimens. Let's get into that. Dr Costello, can you share data from the GRIFFIN study that was presented at the IMS 2022 meeting and your takeaways?
Caitlin Costello, MD: We know that the primary endpoint of that trial was looking at the stringent complete remission rates of these patients after consolidation. These patients underwent induction followed by autologous stem cell transplant followed by consolidation. At consolidation, we are evaluating their stringent complete response rates. Originally, we could see when their initial data was coming out at planned interim analyses, we could see that there was significant improvement in this particular endpoint with the quad patients compared to the triplet regimens. At the recent update, we received the final analysis here at IMS. We're very excited in 2022 to see that we can finally understand that after 2-year follow up now; I think it's a year, maybe, after their final follow-up of either withdrawing from treatment or finishing up the final planned therapy. We can see not only a significant improvement in stringent complete responses, but we're also seeing improvement in MRd negativity rates and the durability of MRd negativity rates. It's getting harder and harder to ignore the fact that quad regimens really are quite effective for these patients, both to achieve initial deep responses, but also to provide durability.
Surbhi Sidana, MD: That's great. We also saw that there's statistical significance with the PFS data with PFS being better for the quad than the triplet. Does that change our clinical practice? Are you using quads for all your transplant-eligible patients or not?
Caitlin Costello, MD: Great question. The PFS data is very hard to ignore. I would like to be an OS girl, I'd like to say overall survival is such an important part of what we do because if we're not saving lives, what are we doing? And we're waiting for those surrogate endpoints, I think because have this luxury of having to wait for time to pass by to understand if there's a difference in survival. PFS, maybe that's going to be an important one, maybe the MRD negativity is important one, but I think realistically we are seeing such dramatic improvements that are hard to ignore. If we're seeing patients are having longer PFS and longer and deeper responses that are more durable, my practice, I've really started initiating dara-RVd in the majority of my transplant-eligible patients.
