Ola Landgren, MD, PhD: Dennis, you brought up that you could offer the patient to collect stem cells and forgo the transplant up front. That’s where the field is right now. There’s a lot of controversy. When talking about who’s transplant eligible, who should be offered to collect stem cells? The question is whether you do it, but let’s talk about who is eligible.

Dennis Verducci, APRN: Most institutions have an age cutoff of about 65 years old. A lot of institutions will transplant if the patient is deemed to be high risk. But this is very controversial. With the introduction of immunotherapy in the induction setting, patients are achieving a deep and durable remission. It’s eradicating the disease. That transplant would be controversial, to say the least.

Ola Landgren, MD, PhD: Ben, do all institutions in the country find this controversial? Are there still places that transplant patients?

Benjamin Diamond, MD: All over the country you’re going to get different answers to this question. That’s because it’s an area of deep controversy. But with more data, we’re seeing that transplant isn’t necessary all the time. It’s not necessary to do an up-front transplant. We’re sometimes seeing that we can get the same PFS [progression-free survival], the same bang for our buck with a salvage transplant. That raises the question: if it isn’t changing the outcome of the disease, if it’s not changing overall survival [OS], then maybe we should just consider it another tool in our armamentarium and not part of the necessary frontline therapy.

Ola Landgren, MD, PhD: Ben is saying it may or may not be necessary. What about OS, Dickran? There have been 2 recent trials randomized: the DETERMINATION trial from Dana-Farber [Cancer Institute] and the IFM 2009 trial. They looked at the use of up-front vs delayed transplant, and both showed a strong benefit for PFS if you look at transplant up front vs delayed. What about OS? For example, what if you look at response for MRD [minimal residual disease] status? What does PFS look like in those trials?

Dickran Kazandjian, MD: That’s a great question, Ola. Thank you. Some of the earlier studies comparing transplant vs not showed some OS benefit, but when you dig deep down, those induction regimens and consolidation regimens aren’t what we’d consider standard of care in this day and age. That’s why those 2 studies you mentioned are so important, because they are the backbone of modern induction therapy for newly diagnosed myeloma, specifically VRd [bortezomib, lenalidomide, dexamethasone]. Neither study has shown any benefit in OS with the use of transplant vs not. More important, in patients who were able to attain an MRD-negative remission, there was no PFS benefit either.

These are important points. In my clinic, for patients who are MRD negative, you have to dig deep to find the reason to go ahead with high-dose therapy and transplant. But for those who are positive, it’s more of a discussion with the patient. Because there’s no OS, in my opinion, you get another therapy. In this case, it’s called high-dose melphalan. For the patient, is it better, or does that patient want to receive that earlier with the knowledge that they can go longer before the myeloma comes back? For them, is it better not to receive that therapy? Even if the myeloma comes back sooner, we have tons of novel therapies coming out that they can receive. It’s a conversation.

Transplant has been very important. It was the first agent in early 2000 that changed the natural history of patients with multiple myeloma. However, as time goes on, instead of it being perceived as the nucleus that all other therapies are based on, it’s another tool in the myeloma experts’ toolbox.

Ola Landgren, MD, PhD: These are very important things you’re bringing up, but these are areas of controversy. There are a lot of opinions. Everything we’re articulating may have individuals agreeing. I’m sure people are disagreeing. But it’s also a vehicle for new research. There are studies investigating this. Ben, what’s high-risk disease? Is it captured accurately when you do FISH [fluorescence in situ hybridization] and cytogenetics? Or do we need better tools?

Benjamin Diamond, MD: For better or for worse, we define high-risk disease based on FISH. This is cytogenetics, and we’re basing these on some of the canonical translocations, the 4;14, the 14;16, and sometimes the 14;20, and the presence of a couple of others, like the gain of 1Q specifically when there are multiple copies greater than 3, and also deletion of 17p. We’re limited to a certain degree by the use of FISH because it’s an aging technology that has differences in the way it’s reported between institutions. It’s dependent on a certain number of factors. We do need to advance the field, but as we look at all the literature available, that’s what we’re basing it on.

Transcript edited for clarity.