Do myeloma cells get included in the stem cell collection and infusion during ASCT?

Do myeloma cells get included in the stem cell collection and infusion during transplant? The reason we have a certain number of cycles before we collect your stem cells is twofold. One is you want to control your disease, right? You want to show that your disease is in remission. We know the outcomes are better, the better remission you're in. And so that's why you get at least three to four cycles of therapy. The reason we don't go to eight to twelve cycles ideally is because even though we may be able to get you into a deeper remission, you also start to accumulate more side effects. We also know that the subsequent cycles sort of have a less and less of an effect on clearing your myeloma cells. But the real reason we don't like to go in too much further is that some of the drugs, including Revlimid, can actually start affecting your ability to collect your stem cells. And so it will make it more difficult to collect those stem cells. So for many reasons, we have sort of this truly arbitrary number of cycles that we do before we collect your stem cells. In terms of whether your cells could be contaminated with myeloma, the answer is yes. And that will happen regardless of how many cycles of therapy we get because, as you know, we can't get rid of all myeloma cells with just those initial treatments. The good news is that the processing of the stem cells and the subsequent freezing of the stem cells is very toxic to myeloma cells. And they don't usually survive very well. And so in general, once we give you back your product, it tends to be pretty clean of myeloma cells. And actually, there were these very large studies done in like the 80s and early 90s about what we call purging of cancer cells in the stem cell product by using antibodies, trying to really clear the cancer cells and just giving you back the stem cells. And what we found was that actually that did not translate to any benefit. But what happened is it really caused some damage to the stem cells that it took much longer to recover. And people were staying in neutropenic phases longer and having more complications. So we don't do that anymore. So the risk is theoretical, but it's a great question. We found that even if a patient has a positive marrow for plasma cells that are malignant, in other words, the myeloma is still present under the microscope, or through something called minimal residual disease testing, which is a more sensitive test, you still can collect stem cells. We found that as long as the plasma cell burden is less than 10% and we prefer less than 5%, we can more often than not collect stem cells and find no detection of the malignant plasma cells in the stem cell collection. So we do recommend doing that. It would only be patients who have refractory disease or don't respond very well that they likely need to get some other treatment beforehand. And you might even call that a consolidation before the stem cell transplant as opposed to afterwards. So you want to be at a low enough tumor burden that you're not worried about giving back that are malignant as part of the stem cell rescue. And that almost never happens unless there's a tremendous amount of disease present at the time of stem cell collection, which most people won't collect. So in overwhelming majority of patients, we significantly decrease the myeloma burden in the bone marrow. Whatever residual cells are there, even in their presence, patients can still get very deep responses and durable responses. So of course, we and others have tried to remove those cells from the graft. So those studies were done. But unfortunately, the technology and the available methods are not good enough to do that. So when people have tried to remove myeloma cells from the graft in the lab, either by using antibodies or only by selecting stem cells so that you can get rid of myeloma cells. And when they did the transplant with that approach, number one, it did not improve their remission status. Those patients had almost the same progression free survivor as the one who got the so-called unpurged, unmanipulated stem cells. And the second thing was that not only we could not adequately remove the myeloma cells from the graft or from the harvest, we adversely affected the quality of graft. So these patients actually had a little delay in the recovery of their white blood cells and platelets. And not only that, we were actually removing some of the competent cells of immune system from the graft and trying to remove the myeloma cells. So these patients actually suffered more infection. So based on the available technique, yes, it's actually safer and in some ways better to go with what you have rather than trying to manipulate and remove more cells from the graft. Thank you.