Who should consider ASCT as part of induction? Why consider ASCT if in a complete remission?

Who should consider autologous stem cell transplant as part of induction? Why would you consider autologous stem cell transplant if you are in a complete response? So transplant transplant is still one of the great therapies of myeloma. Do we still need it? So let's rewind the clock 40 years. Back then our induction therapy, our basic treatment for newly diagnosed myeloma patients was so bad. We compared bad chemo versus transplant, transplant did better. No-brainer. But our therapies have gotten better throughout the years. So in 2009 they started this big study called Determination. And they say, well, we're going to give you VRD, Velcade Revelmidexamethasone. Or they're either going to give you a transplant or not. And a lot of patients and people listening may have gotten that type of therapy. And so far this data set has shown that if you get a transplant as part of your upfront therapy, you stay in remission longer. You have an improved progression-free survival or PFS. But so far in that study, you don't have an increase in your overall survival. You don't live longer. So there are certain subpopulations that we're looking into to really figure out who benefits and who doesn't. Because you will never do worse if you have a transplant. The big question is, do you get a day extra, a month extra, a year extra, 10 years extra? That's what we're trying to figure out right now. What it's probably going to look like is some combination of how deep your response is and what your cytogenetic risk stratification is. For example, for me personally, if I have a patient that doesn't get a complete response and still has measurable disease after induction, I really want to incorporate transplant. But if you get a complete response and you have good risk disease, maybe you don't benefit it enough as much. So I think it's an ongoing discussion between you and your healthcare team. And I think if you're treating the local community, when in doubt, refer or please get referred to a transplant center to have that discourse about the risks and benefits for you as an individual. Over a long time now, we've known that the use of high dose melphalan or high dose conventional chemotherapy has been very effective at controlling myeloma disease. Prior to the availability of a lot of our newer treatments, it even probably allowed people to live longer with the disease. And it really does a very good job of mopping up most of what's left after going through the initial three or four drug regimens that a patient would go through. Melodil has a very strong role in people who do go through transplant. We know from several large studies that have been published recently that people that go through transplant have the disease under control for longer and live longer with the disease controlled than those who do not go through transplant. What we're trying to tease out, and at this point it seems to be the case, people that go through transplant don't necessarily live any longer than those who do not go through transplant. So it's a very long conversation that I have with patients and that I think a lot of transplanters are having. People with high risk cytogenetics, people with high risk features, tend to derive more benefit from transplant. So I think we more strongly encourage it for those patients. And I think it's always a good idea to at least get stem cells collected in the early timeframe to have transplant as an available option down the line should you choose to do it. For most patients at this point, it still has, who are healthy enough to go through transplant, we do a lot of testing to make sure that they're able to and that they are fit to do so. I think for most people it still has a pretty valuable role in their treatment, but it is a longer conversation because it is a little bit of an inconvenience and definitely has an impact transiently on quality of life. So for not all people it's the right decision and for not all people it is immediately after their induction is it the right decision, but at some point might be. The question that comes up is of course if you have given the four drug combination or if you chose the three drug combination, you have collected the stem cells, would it be reasonable to do a transplant if the patient is MOD positive or should you still offer the patient to go right to maintenance? So there is no randomized study that definitively have answered this question. So in my practice I usually give four cycles, I use as a default four drugs, so I use four cycles of four drug combination. I would collect the stem cells and I would give another four cycles of combination therapy as my default and I would check for MOD status after that eight cycle and if I do it that way I have over 70% of my patients being MOD negative at that point. I would offer them to keep the cells and go to maintenance. If the patient want to do a transplant we can certainly offer that, but the 30% or so that currently are MOD positive, I would say to them that we would in this situation recommend a transplant but we are not going to force anyone to do it. And many patients say what if I did just two drug combination, what's the likelihood of achieving MOD negativity? Well if you look through the series that we and others have it's probably around a 30% about probability if you're MOD positive that you turn negative in the coming year. You could argue back and forth and say that you should really transplant to minimize all the risks. I personally think that there are so many components to it. Transplant is quite intense therapy and you will get sick, you will be in a hospital, you will be immunocompromised, you have long term potential toxicity. But you could also argue and say that you could also hold the disease away for a long time. We have known that for a long time. So I let the patient be part of that decision making and I'm not going to force the patient one way or the other. I would give the patient the option and we would have to discuss on a case by case basis. Why would you consider transplant if you are in complete response? What if you were MRD negative? We know that even patients who have had a very good response or complete response, which would be no detection of the myeloma proteins in the blood and then also in the bone marrow, generally still have myeloma somewhere in their body. And so patients even with these deep responses tend to still have their disease under control for longer than if they go through transplant, then not. So still derive that benefit. Now there's an added question, an added layer to that. Well what if they have negative minimal residual disease? And so I think a lot of myeloma specialists are now checking minimal residual disease after their first line of induction before deciding on going forward with transplant. And in those patients the question becomes even harder whether it really is worth all of the effort and the issues that come with transplant if they've had such a deep response already. But I still think it's definitely worth considering and we do know that people that go through transplant at some point in their lives seem to have the disease controlled for longer and have longer intervals without lots of treatment than those who kind of delay it or don't do it at all. Because autologous stem cell transplant is still a component of the standard of care. I personally believe the autologous stem cell transplant will not go away. It will have to be integrated at the appropriate time point. But in addition I also believe we may even have more transplants coming up because with the novel drugs that I just mentioned, BCMA targeting therapies, we may get patients back into a remission that would have otherwise not have had the chance to get into a remission and now we can consolidate with an autologous transplantation. So these are all the new developments and all the questions that arise that we need to answer over the next few years.