At what point in treatment should ASCT be considered?

[Music] at what point in treatment should stem cell transplant be considered and is there a best time to have it there are four times or four reasons for getting a transplant the first is upfront transplant when you're newly diagnosed the second is delayed transplant after some therapy the third is Salvage or second transplant essentially a second transplant after you've already had one and the fourth is to bring your numbers down in preparation for a clinical trial most of the transplant that we do for myeloma patients is done as what we call an upfront transplant that means the person gets diagnosed with myeloma we kind of decide with the person's candidate for transplant in such patients who are eligible after a period about four or five months of initial therapy that is designed to control the disease and we feel that the person is fit enough to give us stem cells to collect and freeze and then we take them immediately to transplant that is called an upfront transplant most of the transplant studies that were done which established this modality of treatment we're done in the setting where patients got initial treatment for about four to five months then got an autologous transplant sometimes a tandem transplant where you get two back-to-back versus they were compared with people who just continued on chemotherapy these studies have shown that the people who got a transplant had a longer remission we call that a longer progression free survival which means they had a time of remission or freedom from progression of myeloma that was longer than if they just continued on chemotherapy and in some of the cases they had a longer overall survival which means that if you follow these patients out for a greater length of time the people who got transplant ultimately lived longer even after multiple relapses etc autologous transplant got established in the early 90s and have to this day always in every study that has been done has provided a longer progression free survival for the patients who got that versus discontinued on chemo so that's the role for up front transplant high-dose melphalan with that oolagah stem cell transplant or risk you should be considered for newly diagnosed myeloma patients I don't put age as a number but if patients are fit or even intermediate fit they should at least have a discussion but I think you know having that conversation is important in the newly diagnosed setting you can also have a transplant in a person who stored their stem cells up front but then chose for whatever reason not have a transplant right away and then when they relapse after the first line of chemotherapy fails they could have a transfer at that point that we call that delayed out logs transplant if the patient's for some reason decide not to get a stem cell transplant or did not have access to it as part of their front line treatment or had at least three and a half to four years benefit from the first one and they're still young and that would still be an option they should be offered that opportunity during their first relapse the more advanced myeloma patients get you know the less bang for the buck you get with high-dose melphalan the third setting is when someone who has had a transplant and they were in remission for several years when they relapse they can get another treatment which puts them back in remission and then get a transplant to make that response last longer too so we call that Salvage transplant you know I don't like that term but you know that's what people call it in the relapsed refractory setting in a more advanced patient where you already have the stem cells stored up in the freezer when the blood counts are declining we tend to utilize high-dose melphalan with stem cell rescue to help augment the patient's blood counts because if the blood counts especially the platelets if they're low patients may not qualify for a clinical trial so that's where we would utilize it you know it would be a temporizing measure to get patients to a clinical trial why is upfront transplant the best option for anyone considering this treatment one of the questions I get asked a lot from patients is that should I do a transplant now should I do it later I think when it comes to an autologous tramps ounce or the standard transplant that we do for myeloma most of the data would point to the fact that you should do it earlier in the disease because that gives you a longer first remission and a longer first remission translates to basically better quality of life because you got a long first remission say four years which is the average you get these days four to five is the average we code for patients with standard risk myeloma myeloma then becomes a blip in your life for about six months that happened four or five years ago the biggest advantage I see to doing a first transplant is that five years later given the history of how we've been treating myeloma so far your choice is in terms of drugs to treat your first relapse five years later from your diagnosis so much better so I've shared these data from a big the National myeloma working group study that we did collecting data on more than 7,000 newly diagnosed myeloma patients going through stem cell transplant trials around the world showing that patients who get to a complete response or better during their first year of diagnosis have almost a three year overall survival benefit compared to those who did not achieve complete response the reason why I bring that up is making the best available strategy to get your patients to the best depth of response during that first year of diagnosis is important you know historically we have had examples and anecdotes of patients doing exceptionally well with just a little bit of treatment but those are exceptions they're not the rules and you know and when you look at data you don't say oh you know there there was once a patient that I treated with just salt and and they did well for 15 years you don't say that you know you look at the data objectively and you look at the whole population and then you come out and make a statement I think it's important for us to you know consider that so depth of response is important what you do for our myeloma patients during that first year of diagnosis is very important that's our best chance to get patients to MRD negativity so in in that context I think at the current moment high-dose melphalan gives that patient was coming to see you the best chance of getting the depth of response in combination with the rest of your therapies it should still be considered a standard of care they still think it's reasonable for patients to consider high-dose therapy especially if they're younger because as you get older it may be a little more difficult to tolerate the high-dose mal plan it's not fun it can be anywhere from one to three months of recovery from that because it does where the patient down and a lot of patients even if they're they have cap recovery we'll call them saying they're quite fatigued and it can take several weeks to get over that pettite but usually by three months after the stem cell transplant most patients are back to close to normal and definitely by six months and most of our patients if they're young and have a job are usually back to work within three months now it depends if they do heavy duty annual labor it may need to be longer it's a desk job it's probably shorter but even then some people have trouble cons Trading why because they're feeling tired from the effects of the high-dose melphalan are there reasons to delay transplant for anyone considering this treatment stem cell transplant still has a role and when you compare it to no transplant you obviously have great advantages both in terms of response in terms of duration of remission in terms of overall survival life expectancy but the question about up front versus delayed transplant and there one can come up with the argument that well even if i delay the transplant and studies have been done there is two large randomized trials one early on in 1998 by the French group and the second one in 2017 by the other French me but by incorporating all the newer treatment and they both more or less showed similar results that with upfront stem cell transplant versus delayed transplant more patients achieved complete remission so depth of response is there with upfront transplant versus delayed transplant number two progression-free survival is longer with upfront transplant but overall survival was about the same but then especially in the more recent trial given on the treat effective treatments for myeloma we may want to wait a little longer before we say that overall survival is about the same but one can make an argument for a delayed transplant that well I would rather delay treatment to later but my counter-argument to that would be that if your intent is to achieve the deepest in the most durable remission then this upfront is the time because we know that with modern treatments based on some of the recent trials the first remission can last on average between five and a half to six years and it could be much longer in patients who have deeper remission or who do not have high-risk chromosomal abnormalities so you achieve a deep and durable remission post transplant sure patients do need treatment but in this day and age that treatment is quite manageable and clinical trials have shown that patients have taken lenalidomide for extended period of time or even high-risk patient have taken a proteasome inhibitor where there is bortezomib and now of course more data coming out with excessive m so you can do upfront transplant and you can stay on maintenance treatment maintaining a fairly decent quality of life and this was shown in actually the French study that was done in the 90s some of the other arguments in favor of upfront transplant that I made to my patients also include that you want to get a more intense treatment when you are younger and in better health again with time no one gets younger and with time of course we can develop other diseases so later on you may not be eligible for high-dose therapy either because of age because of some other morbidity that someone developed sometimes it's a disease that has become more resistant and you get much less out of that transplant then you would get upfront again it's more of a philosophical argument but as a transplant and looking at the overall data I try to convince patients with upfront transplant but I fully respect someone's decision when they decide to delay to a later time [Music]