When should ASCT be considered? When is the best time to have an ASCT?

At what point in treatment should ASCT be considered, and is there a best time to have an ASCT?

Most of the transplant that we do for myeloma patients is done as what we call an upfront transplant. That means a person gets diagnosed with myeloma. We kind of decide with the person's candidate for transplant. That depends on their age, to some extent, their organ function to a bigger extent, which means they have good cardiac or heart, lung, kidney, liver function, and then after a period of in such patients who are eligible, after a period of 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 stem cells to collect and freeze, and then we take them immediately to the transplant that is called an upfront transplant.

Most of the transplant studies that were done which established this modality of treatment were done in the setting. We had patients got initial treatment for about 4 to 5 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. The vast majority of studies have shown that in almost all cases, 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 followed these patients out for a greater length of time, the people who got transplant ultimately lived longer, even after multiple relapses, etc..

So essentially autologous transplants got established in the early nineties 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 upfront transplant.

You can also have a transplant in a person who stored their stem cells upfront but then chose for whatever reason not to have a transplant right away. And then when they relapse after the first line of chemotherapy fails, they could have a transplant back point that we call that delayed autologous transplant. And then the third setting is when someone who has had a transplant and they were in remission for several years, they when they relapse, they can get another treatment which puts them back in remission. And then get the transplant to make that response last longer. So we call that a second salvage transplant.

So the question of whether or not one should get an autologous stem cell transplant is a question often asked in the clinic, and it can be very confusing to many, many patients. And the second question to that is should we get it upfront or can I hold off and get it at a later date? We have data now in the context of an autologous stem cell transplant, and we've done a large trial We've then randomized people to either get a transplant or not get a transplant, and then they've gone on to maintenance. And when you look at that data, the data shows us that patients who got a transplant had a significant benefit in terms of disease control, and it was as high as 18 months. But then if you look at overall survival, there was really no difference.

So I think simplistically putting it, I think it's an important conversation to have with your ecologist. I think collecting the stem cells is a no brainer. High dose melphalan with autologous stem cell transplant or rescue should be considered for newly diagnosed myeloma patients. I don't put it as a number, but if patients are fit, or even intermediate fit, they should at least have a discussion. But I think having that conversation is important in the newly diagnosed setting.

If the patients for some reason decide not to get a stem cell transplant or do not have access to it as part of their front line treatment, they should be offered that opportunity during their first relapse. You don't get as much bang for your buck. The more advanced myeloma patients get the less bang for the buck you get with high dose Melphalan.

In the relapsed refractory setting, when the blood cancer 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 will utilize it. It would be a temporizing measure to get patients to a clinical trial. So those would be the three buckets newly diagnosed setting, whenever you can. First relapse setting for those patients who did not get it the first time around or had at least three and a half to four years and benefit from the first one and they're still young and that would still be an option. The third would be to improve the blood counts in more advanced patient where you already have the stem cells stored up in the freezer.

So I've shared this data from a big international myeloma working group study that we did, collecting data on more than 7000 newly diagnosed myeloma patients going through stem cell transplant trials around the world, showing that patients who get 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.

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 when you look at data, you don't say there was once a patient that I treated with just salt and they did well for 15 years. You don't say that. You look at the data objectively and you look at the whole population and then you come out and make a statement. So I think it's important for us to 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 that context, I think at the current moment, high dose Melphalan gives that patient who's coming to see you the best chance of getting that depth of response in combination with the rest of your therapies. So it should still be considered a standard of care. I 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 Melphalan. It's not fun. It can be anywhere from 1 to 3 months of recovery from that because it does wear the patient down and a lot of patients, even after they have count recovery, will come saying they're quite fatigued and it can take several weeks to get over that fatigue. But usually by three months after the stem cell transplant, most patients are back to close to normal and definitely by six months.