Outcomes With Transplant in Myeloma

Transcript:Amrita Krishnan, MD: Mortality is now—if you look, the Mayo Clinic had a nice review of about 1000 transplants—it’s less than 1%.

Paul Richardson, MD: One thing I would argue though, and this is one we have to be very careful. What did you think of the data presented from our own group and from John B. Hynes Veterans Memorial Convention Center at IMW [International Myeloma Workshop], looking at whole genome signatures in melphalan relapse? That’s from disease.

Sagar Lonial, MD, FACP: If that were the case, then why in our 1000-patient series is the median PFS [progression free survival] between 66 and 72 months? That’s amazing, and our secondary malignancy rate is 3%.

Paul Richardson, MD: If I may, Dr Lonial, those are outstanding results and I think that that’s certainly remarkable. I think, in terms of our randomized trial, that secondary malignancy signal is comparable, but it’s dominated in the transplant arm. What we’ve also learned is that this association with CHIP [clonal hematopoiesis of indeterminate potential] that CHIP is probably higher in myeloma patients. That’s clonal hematopoiesis of indeterminate potential. In those patients, there’s real risk. We’ve actually, from our own series of patients, from our own database, demonstrated that the incidence dramatically increases in that CHIP-positive group. There’s a very interesting construct there. By the same flip, if there’s a genotoxic injury that results in a long-term effect, is that true about the disease? Is there a recurrence of disease that is in a subset—obviously not everyone, far from it—that is adverse, and can we predict who they are?

Kenneth Shain, MD, PhD: The whole point is that our job is to provide the best care, the optimal care, for our patients. Right now if I want to say what is the best odds of having a good outcome, it involves the sequence of therapy. I sat there with patients and I tell them, I can give you the odds, I know not everybody needs transplant. I don’t want to transplant everybody because there are other toxicities. Right now, to give you the best odds of good outcomes, we need to have this sequence of therapies.

Paul Richardson, MD: Based upon what we have now.

Kenneth Shain, MD, PhD: As we can start learning, is CHIP going to tell us we shouldn’t do it? These are all things. How can we prove Amrita’s point is that, “Who are the patients who don’t need it”? The no hypothesis is transplant, in my mind. And then how do we prove those who don’t? Because there are patients who do very well without it, but we aren’t that smart yet. We haven’t figured out how to identify those individuals. We need to figure out how to identify those individuals so we can say, “You do not need this kind of therapy”. These patients do.

Ajai Chari, MD: I think we’re talking about medical risk and benefit, but there are also issues with treating to progression. These KRd [carfilzomib, lenalidomide, and dexamethasone] regimens, which are looking so powerful—are real-world patients going to get 8 to 12 cycles of KRd? So there’s a medical risk benefit and there’s the cost as a society. What is cost-effective? Then the last is also quality of life. I think when we have regimens that are potentially approaching medical equipoise in terms of risk-benefit, we have to think about the cost and quality of life issues as well, and I think those 4 variables need to be integrated.

Paul Richardson, MD: I think that the most important thing to me, at least, is there is a future? The future is dramatic. We’ve got cellular therapies which we’re going to come on to and, biologically and for lots of reasons, one wouldn’t expect them to carry the same baggage that phenylalanine mustard does as an alkylator.

Amrita Krishnan, MD: It sounds so bad when you say it.

Paul Richardson, MD: That is actually what it is.

Sagar Lonial, MD, FACP: Just wait till he gets to melflufen.

Paul Richardson, MD: It’s the same principle: hitting that stemness but at the same time without the collateral damage. So then, I think Amrita has a really lovely summary of newly diagnosed and what to do transplant-eligible.

Transcript Edited for Clarity