[Music] i think dr fonseca expressed uh the situation quite well i can add a couple of things though uh number one as dr raphael fonseca pointed out there are two ways to use mrd one one is for the regulatory reasons that is if we use it in our studies perhaps we can get answers more quickly as to for example which drug drug a may be better than drug b because it achieves a deeper mrd more frequently the other way to possibly use mrd is in an individual patient that is to make clinical decisions and this is still somewhat controversial in the world of myeloma there are many of our colleagues who don't necessarily believe that that it's time to use mrd to make these clinical decisions i think dr fonseca and i are in the group that feel that it is often helpful it's not always helpful but it is often quite helpful and as dr fonseca said in our institution our goal is also to achieve the deepest mrd possibly possibly mrd negativity zero in a million i'm going to show you a couple of slides of patience in a second to show you what what i mean by that and then we can open it up for questions one of the things we haven't mentioned yet though is that in myeloma unfortunately the the best way to measure mrd is with a bone marrow procedure and many of you are familiar with bone marrow aspirate and biopsies we are not yet at a point where we can use peripheral blood to make those decisions as we can for example in leukemia or lymphoma so i think that's one of the major reasons why physicians and patients aren't using mrd as an endpoint or as a con a clinical decision-making point because it's it's relatively hard to get it and the patients are uncomfortable when they have the procedure the day will come when we will be able to measure in the peripheral blood and i think when that day comes everybody in myeloma will be using it just as we use light chains or m spikes i'm going to share can we share my slides again here and just showed a couple of cases this first one is a patient who happens to be also a friend of mine who in 2011 after a transplant and a year of revlimid could not tolerate lenolidomite or revlimid any longer because of a lot of side effects and low blood counts um and we decided to to not treat him with uh with maintenance you can see here starting in 2014 in july i started doing a bone marrow on him every july he volunteers as a subject when i demonstrate to our new fellows how to do a bone marrow so every the first week in july every year we do a bone marrow on him and every year he's had zero in a million malignant cells i think confirming in my mind maybe hopefully in all of yours that this guy would have just done just as well he did just as well without therapy as he would have done with lenolidomide and he would have had eight or nine or even ten years now of um of toxicity so there are there are patients taking lenolidomide now who probably don't need it as maintenance there are other drugs being given as maintenance too where we hope that someday we could figure out a way perhaps using mrd to know in which patients we can stop uh this maintenance therapy because it's also costly of of course this is another case a similar case in which i had a patient with high risk disease deletion 17p um we tend to give after transplant triplet therapy this patient got revlimidvalcade dexamethasone for many many years and then revlimid for many years and after um five years was just so tired of therapy she began to ask if she couldn't finally stop therapy and i had been measuring mrd in her and you can see that early on after the transplant she had 18.8 million cells in a million dropping to four and then zero and over the next five years four years in this slide but still five years now um she had either zero or two malignant cells in a million and finally in 2019 we stopped her maintenance similar to the other patient um and she's done fine since then i haven't put it on here but she had another zero just recently after being off of revlimid for a year so these are two instances where i think mrd is quite useful in the clinical management of patients i'm going to show you one more slide then we'll open up for discussion this is some patients present with renal failure and need dialysis this is a gentleman who did and after a number of years of therapy and on dialysis and having a couple of mrd negative uh results we convinced our kidney transplant doctors to do a related kidney transplant for him and he's been off dialysis now for four years um remains in remission and uh and we've convinced the kidney transplanters that anyone who achieves an mrd zero should be eligible for kidney transplantation um can we discontinue my slides please so at this point we can open it up for discussion there are obviously many other areas we could be using mrd for clinical decision making and dr fonseca and i would be very happy to to discuss this with you you