BETA - If I am not eligible for transplant what treatment options should I consider?

A common question we get in the clinic is whether someone is eligible for transplant and it's a question that sometimes creates disappointment because I'm not going to be able to go through the transplant. And varying that question is an assumption that transplant is the only or it's necessarily the best treatment. And the short answer to that is no. I do believe transplant is one of the options but it's not the only path to move forward with the treatment for myeloma. And the reason we talk so much about this eligibility or not is that there is no question in my mind that as we go on life, transplant can become a much bigger burden in individuals who are older. Nowadays we say most patients under 65 should consider going through a transplant. Most patients over the age of 75 probably should avoid transplant and then somewhere between 65 and 75 there's some adaptation based on the fitness and the strength of the person. But if I were to tell someone you're not going to be eligible for transplant, what are some of the treatment options? The short answer is they're actually very good treatment options. In particular, I think of all the options we have, there's a clinical trial that was called the Maya clinical trial that looked at the combination of daratumumab, lenolidomide, rabumid, and dexamethasone. That trial gave us to what we would describe with superlative terms great results because the durability of the control of the disease is quite long with that. It has been estimated to be over five years. Now five years is the median. That doesn't mean that someone puts a clock and you get five years. That means that if you take 100 patients at the end of five years, half of those patients would have required a change of treatment, something new. The other half are still doing very good. So we like that treatment as simple as I tell patients always easier said if you're sitting in the doctor chair, but it's very well tolerated. It's probably one of the most best tolerated treatments we have. We have seen that it can result in significant prolongation of survival. We did a study just recently using this big database is what we call the simulation where we asked ourselves the questions. If you start with a treatment like this and then you were to assume that someone who's not transplant eligible were to get a second treatment with either carfil some of our pomelotomide estimated that for a patient like that we would have a median survival that would exceed nine years. So with that in mind when I see patients now you know if you're over 75 I usually will avoid transplant but I'm even questioning whether we should be doing transplants between 70 and 75 and I'm sitting in front of that person I think you know if this was my mother or my father how strong would I be pushing forward with transplant and knowing what I know about that study we did I would say less so. I think it's reasonable to consider not going to transplant for that patient population. So hopefully you know this provides an explanation so why not necessarily being transplant eligible. It's a terrible thing. It's just a reflective you know stance of where we are in life. Of course we all want to live to 120 but most of us won't and that means that if you're 75 let's say and you start with one of those new treatments your life expectancy is going to be pretty close to normal life expectancy. So we have good options for those patients. As far as the eligibility for transplant it probably varies by country and program and for example in Europe there may be cut off age cutoffs at age 65 or similar whereas in the U.S. we don't typically have a specific age cut off. I think Medicare may require patients to not be over 80. Typically it's very common to have patients that are eligible for stem cell transplant up into 75 but when they're between 75 and 80 it's on a case by case basis depending on their physiologic function and how fit they are and if they're not having any frailty issues then certainly it's still an option for those patients. So typically it's going to be if they have organ dysfunction if they have you know cardiac dysfunction or lung dysfunction those patients may be ineligible or if they're more frail they we may not want to do a toxic more potentially more toxic stem cell transplant for those patients but never fear we you know we do have excellent options for patients that either don't qualify or don't want to do a stem cell transplant. We are typically doing anti-CD38 monoclonal antibody based frontline induction therapy for myeloma these days whether it's pre-transplant or for the non-transplant patients. If we're being aggressive and the patient's younger and fit and really definitely wants to go to transplant we're often doing quadruplet therapy with daratumumab, linalytamide, bortezumib and dexamethasone prior to transplant and those that are not going to transplant will still use daratumumab and combined with linalytamide and dex triplet therapy and those patients according to the mya study have very good outcomes and about five years into treatment more than half of them are still in remission even without a stem cell transplant. The reason that we still do the stem cell transplant when able is that well partly because of the determination study recently showed that if we compare patients that had novel therapies for induction and then either go to transplant and first remission or don't do the transplant the ones that did the transplant and first remission had on average of about 22 months longer remission compared to the ones that did not so close to two years longer progression free survival or remission as we call it and so we you know certainly in the patients that can tolerate it we typically still try to do that however that study did not use daratumumab in the frontline setting and so we don't really have a direct comparison of daratumumab based induction therapy with or without stem cell transplant and so though you know those patients in the mya study without a transplant are having you know five or six years of remission without a transplant and the determination with about five or six years of remission and so they may still have pretty comparable outcomes even without a transplant and also those that achieve a molecular or really deep remission after their induction therapy we might also just collect and store those patients stem cells and hold off on the transplant especially if they're not really very excited about going into the transplant as well. If I am not eligible for SCT will that make me ineligible for CAR T cell therapy? The question that could be stated is if you're not eligible for transplant does that mean you won't be eligible for CAR T and the answer is resoundingly no. We actually are doing CAR T's on patients who we would traditionally not think of them as being candidates for stem cell transplant even patients into their their 80s. In addition to the CAR T's we have the options of the bi-specifx. Now the bi-specifx are very interesting because they provide us a little bit more of a control situation so as an example I have patients who have serious medical health issues for other reasons an example I can think of is a patient with severe heart disease coronary disease with heart failure and we felt that person was not eligible for transplant but also we felt that CAR T may have been tricky because once you do the CAR T you're committed for the duration of what the CAR T's are so in that circumstance we elected to go first to a bi-specific because we can control the situation better and I'm happy to report that patient is doing very well.