Podcasts about Bortezomib

Below is a brief video snippet from our conversation. Full videos of all Ground Truths podcasts can be seen on YouTube here. The current one is here. If you like the YouTube format, please subscribe! This one has embedded one of my favorite TikTok's from Will. There are several links to others in the transcript. The audios are also available on Apple and Spotify.Transcript with links to both audio and videos, commencement addresses, NEJM article coverageEric Topol (00:06):Hi, it's Eric Topol from Ground Truths, and I've got an amazing couple with me today. It's Will Flanary and Kristin Flanary, the Glaucomfleckens. I've had the chance to get to know them a bit through Knock Knock, Hi! which is their podcast. And of course, everyone knows Dr. Glaucomflecken from his TikTok world and his other about 4 million followers on Instagram and Twitter and all these other social media, and YouTube. So welcome.Will Flanary (00:43):Thanks for having us.Kristin Flanary (00:44):Thank you. Happy to be here.By Way of BackgroundEric Topol (00:45):Yeah. Well, this is going to be fun because I'm going to go a quick background so we can go fast forward because we did an interview back in early 2022.Kristin Flanary (00:56):Yes.Eric Topol (00:57):And what you've been doing since then is rocking it. You're like a meteoric, right. And it was predictable, like rarefied talent and who couldn't love humor, medical humor, but by way of background, just for those who are not up to speed. I guess you got your start, Will, as a class clown when your mother was a teacher in the sixth grade.Will Flanary (01:22):Yep, yep. I misbehaved a little bit. It helped that I still made good grades, but I cut up a bit in class.Eric Topol (01:32):And then you were already in the comedy club circuits doing standup in Houston as an 18-year-old.Will Flanary (01:40):It was all amateur stuff, nothing, just dabble in it and trying to get better. I was always kind of naturally funny just with my friend group and everything. I loved making people laugh, but doing standups is a whole different ball game. And so, I started doing that around Houston as a high school senior and kept that going through college and a little bit into med school.Kristin Flanary (02:02):Houston was a good training ground, right? That where Harris Wittels was also coming up.Will Flanary (02:07):Yeah. A lot of famous comedians have come through Houston. Even going back to Bill Hicks back in the, was that the 80s, I think? Or 90s?Eric Topol (02:17):Well, and then of course, it was I think in 2020 when you launched Dr. Glaucomflecken, I think. Is that right?Will Flanary (02:28):That's when it really started to take off. I was on Twitter telling jokes back in 2016.Kristin Flanary (02:39):GomerBlog before that, that's actually where it was born.Will Flanary (02:41):I was doing satire writing. I basically do what I'm doing now, but in article form, trying to be The Onion of medicine. And then the pandemic hit, started doing video content and that's really with lockdown. That's when, because everybody was on social media, nobody had anything else to do. So it was right place, right time for me and branching out into video content.On to Medical School Commencement AddressesEric Topol (03:11):Alright, so that's the background of some incredible foundation for humor. But since we last got together, I'll link the Medicine and the Machine interview we did back then. What has been happening with you two is nothing short of incredible. I saw your graduation speeches, Will. Yale in 2022, I watched the UCSF in 2023 and then the University of Michigan in 2024. Maybe there's other ones I don't even know.Kristin Flanary (03:45):There's a few others.Will Flanary (03:45):There's a few. But I feel like you've done, I'm sure your fair share of commencement addresses as well. It's kind of hard to come up with different ways to be inspirational to the next generation. So fortunately, we have together, we have some life experiences and learned a thing or two by doing all of this social media stuff and just the things we've been through that I guess I have enough things to say to entertain an interest.Eric Topol (04:18):Well, you're being humble as usual, but having watched those commencement addresses, they were the best medical commencement addresses I've ever seen. And even though you might have told us some of the same jokes, they were so great that it was all right. Yeah, and you know what is great about it is you've got these, not the students, they all love you of course, because they're probably addicted to when's your next video going to get posted.(04:44):But even the old professors, all the family members, it's great. But one of the things I wanted to get at. Well, I'll start with the graduation speeches, because you were such an inspiration, not just with humor, but your message. And this gets back to you as a couple and the tragedies you've been through. So you really, I think, got into this co-survivor story and maybe Kristin, since you are the co-survivor of two bouts of Will's testicular cancer, and then the sudden cardiac death. I mean, people don't talk about this much, so maybe you could help enlighten us.Tragedies and Being a Co-SurvivorKristin Flanary (05:26):Yeah, it's funny because the experience of being a co-survivor is nothing new. It's as long as we've had human beings, we've had co-survivors. But the concept around it and giving it a name and a label, a framework to be able to think about it, that is what I think is new and what people haven't talked about before. So co-survivor is just this idea that when a medical trauma happens to a patient, the patient has their experience and if they survive it, they are a survivor and they have a survivor experience. And also, most people are closely attached to at least one other person, if not many. And those people are co-surviving the medical event along with the survivor. That event is happening in their lives as was happening to them too. If someone comes in with a patient to the hospital, that person, you can just assume by default that their lives are pretty intimately or profoundly intertwined or else why would that person be there? And so, thinking of it as there's the patient and then there's also a co-patient, that family members in the past have only been thought of as caregivers if they've been thought of at all. And that is certainly one aspect of the role, but it's important to remember that whatever it is that's happening to the patient is also affecting the family members' lives in a really deep and profound way.Eric Topol (07:04):That's really helpful. Now, the fact that you recognize that in your graduation speech, Will, I think is somewhat unique. And of course, some of the other things that you touched on like playing to your creativity and the human factors, I mean, these are so important messages.Will Flanary (07:23):Well, in the discussion about co-survivorship and because I talk about that whenever I do my keynotes and when I do the commencement addresses, but all credit goes to Kristin for really being the driving force of this idea for me and for many others because as a physician, we take care of patients. Our focus is always on the patient. And it really wasn't until this happened to me and my family and Kristin in particular that I started to understand exactly what she's talking about and this idea. And so, Kristin gets a lot of credit for just really bringing that term and that idea to the forefront.Eric Topol (08:09):Yeah, well, you saved his life. It's just not many have that bond. And then the other thing I just want to mention now, you've been recognized by the American Heart Association and a whole bunch of other organizations awarded because of your advocacy for CPR. And you even mentioned that I think in one of your commencement addresses.Will Flanary (08:31):Yeah, I tried to get the crowd to do CPR. Like team up, partner up, and it kind of fell flat. It wasn't quite the right time, I think, to try to do a mass class on CPR. So maybe next time.Eric Topol (08:47):Right. Well, so you had this foundation with the Glaucomflecken General Hospital and taking on 37 specialties and all these incredible people that became part of the family, if you will, of spoof on medicine and your alter ego and these videos that you would do. And sometimes you have three or four different alter egos in there playing out, but now you've branched into new things. So one which is an outgrowth of what we were just talking about. You've been on this country tour, Wife & Death.“Wife and Death,” A Nationwide TourKristin Flanary (09:28):Yes.Eric Topol (09:29):Wife and death. I mean, yeah, I guess we can make the connect of how you named it that, but what is it you've been selling out in cities all over the country, and by the way, I'm really upset you haven't come to San Diego, but tell us about wife and death.Will Flanary (09:44):Yeah. Well, we have this amazing story and all these medical challenges we've been through, and then developing the Glaucomflecken brand and universe, and we've done keynotes together for years, and then we thought, let's have more fun with it. Let's do keynotes. They're great. We can get our message out, but sometimes they're just a bit stuffy. It's an academic environment.Kristin Flanary (10:15):They're usually at seven in the morning also, so that's the downside.Will Flanary (10:21):So we thought, let's just put together our own live show. Let's put together something that we could just creatively, we can do whatever we want with it. I could dress up as characters, Kristin, who has these beautiful writing and monologues that she's put together around her experience and just to create something that people can come into a theater and just experience this wide range of emotions from just laughter to tears of all kinds, and just have them feel the story and enjoy this story. Fortunately, it has a happy ending because I'm still alive and it's been so much fun. The audiences have been incredible. Mostly healthcare, but even some non-healthcare people show up, and we've been blown away by the response. Honestly, we should have done bigger theaters. That's our lesson for the first go round.Eric Topol (11:21):I saw you had to do a second show in Pittsburgh.Will Flanary (11:24):We did.Kristin Flanary (11:26):That one sold out too. Something about Pittsburgh, that was a good crowd, and there was a lot of them.Will Flanary (11:33):It was almost like in Pittsburgh, they rarely ever get any internet comedian ophthalmologists that come through. I don't know.Eric Topol (11:41):Well, I see you got some still to come in Denver and Chicago. This is amazing. And I wondered who was coming and I mean, it's not at all surprising that there'd be this phenomenal popularity. So that's one thing you've done that's new, which is amazing. And of course, it's a multidimensional story. The one that shocked me, I have to tell you, shocked me, was the New England Journal partnership. The New England Journal is the most stodgy, arrogant, I mean so difficult. And not only that.Kristin Flanary (12:17):You said that. Not us.Partnering with the New England Journal of Medicine!Eric Topol (12:19):Yeah, yeah. They'll get this too. They know we don't get along that well, but that's okay. You even made fun of journals. And now you're partnering with the New England Journal, God's greatest medical journal, or whatever. Tell us about that.Will Flanary (12:39):Well, so one thing that I really enjoy doing, and I've done it with my US healthcare system content is almost like tricking people into learning things. And so, if you make something funny, then people will actually sit there and listen to what you have to say about deductibles and physician-owned hospitals and all these inner workings. DIR fees and pharmacy, all these things that are really dry topics. But if you can make them funny, all of a sudden people will actually learn and listen to it. And the New England Journal of Medicine, they approached me with an idea. Basically just to take one or two of their trials per month. And I just make a skit out of that trial with the idea being to help disseminate some of the research findings that are out there, because I guess it's getting harder and harder for people to actually read, to sit down and read a journal article.(13:43):And so, I have to credit them for having this idea and thinking outside the box of a different way to get medical information and knowledge out to the masses. And you're absolutely right, that I have been critical of journals, and particularly I've been critical of the predatory nature of some of the larger journals out there, like Elsevier. I've specifically named Elsevier, Springer, these journals that have a 40% profit margin. And I certainly thought about that whenever I was looking into this partnership. And the reason I was okay with doing it with the New England Journal is because they're a nonprofit, first of all, so they're run by the Massachusetts Medical Society. That's the publisher for that journal. And so, I feel okay partnering with them because I feel like they're doing it in a much better way than some of the bigger journal corporations out there.Kristin Flanary (14:54):Well, and also part of the deal that we negotiated was that those articles that you make skits about those will be available open access.Will Flanary (15:03):Oh yeah. That was a prerequisite. Yes. It was like, if I'm going to do this, the articles that I'm talking about need to be free and readily available. That's part of it.Eric Topol (15:14):I think you've done about five already, something like that. And I watched them, and I just was blown away. I mean, the one that got me where I was just rolling on the floor, this one, the Belantamab Mafodotin for Multiple Myeloma. And when you were going on about the Bortezomib, Dexamethasone. We'll link to this. I said, oh my God.Will Flanary (15:40):Yeah. The joke there is, you don't have any idea how long it took me to say those things that quickly. And so, I was writing this skit and I'm like, wouldn't it be funny if somehow that triggered a code stroke in the hospital because this person is saying all these random words that don't have any meaning to anybody. Man, I tell you, I am learning. Why would I ever need to know any of this information as an ophthalmologist? So it's great. I know all this random stuff about multiple myeloma that I probably would never have learned otherwise.Kristin Flanary (16:21):It's the only way, you won't read a journal either.Eric Topol (16:23):Well, and if you read the comments on the post. These doctors saying, this is the only way they want to get journal information from now on.Will Flanary (16:33):Which is double-edged sword, maybe a little bit. Obviously, in a 90 second skit, there's no way I'm going to cover the ins and outs of a major trial. So it's really, in a lot of ways, it's basically like, I call it a comedy abstract. I'm not going much further than an abstract, but hopefully people that are actually interested in the topic can have their interest piqued and want to read more about it. That's kind of the idea.Eric Topol (17:06):Yeah. Well, they're phenomenal. We'll link to them. People will enjoy them. I know, because I sure did. And tenecteplase for stroke and all that you've done. Oh, they're just phenomenal.Will Flanary (17:20):Every two weeks we come out with a new one.Eric Topol (17:24):And that is basically between the fact that you are now on the commencement circuit of the top medical schools and doing New England Journal videos on their articles. You've crossed a line from just making fun of insurance companies and doctors of specialties.Kristin Flanary (17:44):Oh, he has crossed many lines, Dr. Topol.Eric Topol (17:46):Yeah. Oh yeah. Now you've done it, really. Back two years ago when we convened, actually it's almost three, but you said, when's it going to be your Netflix special?Will Flanary (18:02):Oh, gosh.Eric Topol (18:02):Is that in the works now?Will Flanary (18:04):Well, I'll tell you what's in the works now.Kristin Flanary (18:06):Do you know anyone at Netflix?Will Flanary (18:09):A New Animated SeriesNo. We're working on an animated series.Eric Topol (18:12):Oh, wow. Wow.Will Flanary (18:13):Yeah. All these characters. It's basically just this fictional hospital and all these characters are very cartoonish, the emergency physician that wears the bike helmet and everything. So it's like, well, what do we have together? What do we, Kristin and I have time for? And it wasn't like moving to LA and trying to make a live action with actors and do all, which is something we probably could have tried to do. So instead, we were like, let's just do an animated series.Kristin Flanary (18:48):Let's have someone else do the work and draw us.Will Flanary (18:51):So we've worked with a writer for the first time, which was a fun process, and putting together a few scripts and then also an animator. We learned a lot about that process. Kristin and I are doing the voiceovers. And yeah, it's in process.Kristin Flanary (19:10):We're the only actors we could afford.Will Flanary (19:12):Right, exactly.Eric Topol (19:13):I can't wait to see it. Now when will it get out there?Will Flanary (19:17):Well, we're hoping to be able to put it out on our YouTube channel sometime early next year. So January, February, somewhere around there. And then we can't fund the whole thing ourselves. So the idea is that we do this, we do this pilot episode, and then we'll see what kind of interest we can generate.Eric Topol (19:37):Well, there will be interest. I am absolutely assured of that. Wow.Will Flanary (19:42):Let us know if you know anybody at the Cartoon Network.Kristin and Will Flanary (19:45):Yeah, we're open to possibilities. Whatever, Discovery channel. I don't know.Eric Topol (19:51):You've gotten to a point now where you're ready for bigger things even because you're the funniest physician couple in medicine today.Kristin Flanary (20:05):Well, that's a very low bar, but thank you.Will Flanary (20:08):There are some funny ones out there, but yeah, I appreciate that.Eric Topol (20:11):Well, I'm a really big comedy fan. Every night I watch the night before, since I'm old now, but of Colbert and Jimmy Kimmel, just to hear the monologues. Trevor Noah, too. And I can appreciate humor. I'll go to see Sebastian Maniscalco or Jim Gaffigan. That's one of the things I was going to ask you about, because when you do these videos, you don't have an audience.Will Flanary (20:39):Oh yeah.Eric Topol (20:40):You're making it as opposed to when you are doing your live shows, commencement addresses and things like that. What's the difference when you're trying to be humorous, and you have no audience there?Will Flanary (20:55):Well, whenever I'm filming a skit, it's just all production. In fact, I feel like it's funny. I think it's funny, but it's really not until I see the response to it, or I show Kristin, or what I have is where I really know if it's going to work. It's great to put the content out there and see the responses, but there's nothing like live interaction. And that's why I keep coming back to performing. And Kristin's been a performer too in her life. And I think we both really enjoy just the personal interaction, the close interaction, the response from people to our story.Kristin Flanary (21:36):We do most of our work alone in this room. I do a lot of writing. He does a lot of playing.Will Flanary (21:44):Dress up.Kristin Flanary (21:44):All the people in his head, and we do that very isolated. And so, it's very lovely to be able to actually put names to faces or just see human bodies instead of just comments on YouTube.Will Flanary (21:59):Meet people.Kristin Flanary (21:59):It's really nice.Will Flanary (22:01):We've been doing meet and greets at the live shows and seeing people come up wearing their costumes.Eric Topol (22:07):Oh, wow.Will Flanary (22:11):Some of them talk about how they tell us their own stories about their own healthcare and talk about how the videos help them get through certain parts of the pandemic or a difficult time in their life. And so, it reinforces that this means something to a lot of people.Kristin Flanary (22:29):It's been really fun for me, and probably you too, but to get to see the joy that he has brought so many people. That's really fun to see in person especially.Eric Topol (22:42):No question. Now, when you're producing it together, do you ever just start breaking into laughter because it's you know how funny this is? Or is it just you're on kind of a mission to get it done?Will Flanary (22:54):Well, the skits I do by myself. And sometimes when I'm writing out the skit, when I'm writing the skit itself, I will laugh at myself sometimes. Not often, but sometimes they're like, oh, I know that's really funny. I just wrote a skit that I'm actually going to be debuting. I'm speaking at the American Academy of PM&R, so the big PM&R conference. I'm writing a skit, it's How to Ace your PM&R residency interview.Will Flanary (23:28):I was writing up that skit today and kind of chuckling to myself. So sometimes that happens, but whenever we do our podcast together, we definitely have outtakes.Kristin Flanary (23:38):Oh yeah, we've got some.Will Flanary (23:40):We crack each other up.Kristin Flanary (23:41):We do.Will Flanary (23:42):Sometimes we're getting a little punchy toward the end of the day.Eric Topol (23:47):And how is the Knock Knock, Hi! podcast going?Will Flanary (23:51):It's awesome. Yeah.Kristin Flanary (23:52):Yeah. It's a really fun project.Will Flanary (23:54):We still enjoy. You can work with your spouse and in close proximity and still be happily married. So it's doable everyone.Kristin Flanary (24:06):That's right. And we're in that phase of life that's really busy. We've got kids, we've got a gazillion jobs. House, my parents are around, and so it's like the only time all week that we actually get to sit down and talk to each other. So it's actually kind of like a part of our marriage at this point.Will Flanary (24:28):We're happy to involve the public in our conversations, but we couldn't do it because we have all these things going on, all our hands and all these little places. We can't do it without a team.Kristin Flanary (24:41):Yeah, absolutely.Will Flanary (24:41):And that's the thing that I've learned, because I've always been a very loner type content creator. I just wanted to do it all myself. It's in my head and I have trouble telling others, describing what's in my head. And Kristin and our producers have helped me to be able to give a little bit of control to others who are really good at what they do. And that's really the only way that we've been able to venture out into all these different things we've talked about.Eric Topol (25:12):Well, I think it comes down to, besides your ability to get to people in terms of their laughter receptors, you have this incisive observer capability. And that's one of the things I don't, I can't fathom because when you can understand the nuances of each specialty or of each part of healthcare, and you haven't necessarily interacted with these specialists or at least in recent years, but you nail it every time. I don't know how you do it, really that observational, is that a central quality of a comedian, you think?Will Flanary (25:52):There's definitely a big part of that. You got to get the content from somewhere. But for the specialties, it's really first about just getting the personalities down. And that doesn't change over time.Kristin Flanary (26:08):Or around the world.Will Flanary (26:09):Or around the world. We hear from people from all over the world about, oh, it's the same in Guatemala as it is in the US.Kristin Flanary (26:18):Surgeons are the same.Will Flanary (26:19):Yeah.Kristin Flanary (26:20):Emergency is the same.Will Flanary (26:21):Which has been really cool to see. But so, I draw on my experience interacting with all these specialties back in my med school and intern days. You're right, as an ophthalmologist, we don't get out very much.Eric Topol (26:33):No.Will Flanary (26:35):So very few people have ever seen an ophthalmologist. We do exist. But then beyond that, I do have to include some actual medical things. And so, I actually, I do a lot of research. I find myself learning more about other fields sometimes than I do in my own field. So especially the further out I get from med school, I know less and less.Eric Topol (27:00):Yeah, that's what I was thinking. But you're always spot on. It's interesting to get that global perspective from both of you. Now you're still doing surgery and practicing ophthalmology. Have you reduced it because this has just been taking off so much more over the recent years or keeping it the same?Will and Kristin Flanary (27:21):Nope, I'm still. Do you know how many years I had to come along on all of this medical training? He is not allowed to give this up.Will Flanary (27:29):I know there's something called a sunk cost fallacy, but this is no fallacy. There's enough of a sunk cost. I got to stick with it. No, I still enjoy it. That's the thing. It actually, it informs my comedy, it grounds me. All of the social media stuff is built upon this medical foundation that I have. And if I stopped practicing, I guess I could maybe cut back. But I'm not planning on doing that. If I stop practicing medicine, I feel like it would make my content less.Kristin Flanary (28:07):Authentic.Will Flanary (28:08):Less authentic, yeah. That's a good way to put it.Eric Topol (28:09):Yeah, no, that makes a lot of sense. That's great you can get that balance with all the things you're doing.Will Flanary (28:17):And if I stop practicing medicine, they're not going to invite me to any more commencement addresses, Dr. Topol. So I got to draw the line somewhere.Eric Topol (28:28):One of the statements you made at some point earlier was, it was easier to go to become a doctor than to try to be a comedian. And yeah, I mean you proven that.Will Flanary (28:38):A lot of ways. That's true.Eric Topol (28:40):Wow. I am pretty awestruck about the rarefied talent that you bring and what you both have done for medicine today. And the thing is, you're so young, you have so much time ahead to have an impact.Will Flanary (28:57):You hear that Kristin, we're young. Look at that.Kristin Flanary (29:00):That's getting less and less true.Will Flanary (29:01):Kristin, she just turned 40. It's right around the corner for me. So I don't know.Will Flanary (29:11):We got some years left.Eric Topol (29:12):You're like young puppies. Are you kidding? You're just getting started. But no, I think that what you brought to medicine in terms of comedy, there's no other entity, no person or people like you have done. And just the last thing I want to ask you about is, you have a platform for advocacy. You've been doing that. We talked about co-survivor. We talked about nurturing the human qualities in physicians like creativity and also taking on the insurance companies, which are just monstrous. I'll link a couple of those, but the brain MRI one or the Texaco.Will Flanary (29:54):Texaco Mike.Eric Topol (29:55):Yeah, that one is amazing. But there is so many. I mean, you've just taken them apart and they deserve every bit of it. Do you have any other targets for advocacy or does that just kind of come up as things go?Will Flanary (30:08):It kind of comes up as things go. There's things I keep harping on. The prior authorization reform, which I've helped in a couple of different states. There's a lot of good people around the country doing really good work on prior authorization and reforming that whole process. And I've been able to just play a small part in that in a couple of different ways. And it's been really fun to do that. And so, I do plan on continuing that crusade as it were. There's certain things I'd like to see. I've been learning more about what pharmacists are dealing with as well as a physician. Unfortunately, we are very separate in a lot of ways and just how we come up in medicine. And so, I have had my eyes opened a lot to what community pharmacists are dealing with. For all the terrible things that we have to deal with as physicians in the healthcare system. Pharmacists have just as much, if not more of the things that they're doing that are threatening their livelihoods. And so, I had love to see some more reform on the PBM side of things, pharmacy benefit managers, Caremark, Optum, all of them. They're causing lots of problems.Eric Topol (31:24):I couldn't agree with you more. In fact, I'm going to have Mark Cuban on in a few weeks and we're going to get into that. But the pharmacists get abused by these chains.Will Flanary (31:33):Oh, it's bad. It's really bad.Eric Topol (31:35):Horrible, horrible. I feel, and every time I am in a drugstore working with one of them, I just think what a tough life they have to deal with.Will Flanary (31:45):I guess from an advocacy standpoint, the good news is that there's never a shortage of terrible injustices that are being foisted upon the public and physicians and healthcare workers.Kristin Flanary (31:59):Yes. The US healthcare system is ripe for advocacy.Will Flanary (32:01):Yes. And that's a lesson that I tell people too, and especially the med students coming up, is like, there's work to be done and get in touch with your state societies and there's always work to be done.Eric Topol (32:18):Now you've stayed clear of politics. Totally clear, right?Will Flanary (32:24):For the most part, yeah. Yeah. It depends on what you consider politics. It depends on what you consider politics.Eric Topol (32:32):It being election day, you haven't made any endorsements.Will Flanary (32:36):I haven't. And I don't know. I can only handle so much. I've got my things that I really care about. Of course I'm voting, but I want to talk on the things that I feel like I have the expertise to talk about. And I think there's nothing wrong with that. Everybody can't have an opinion on everything, and it means something. So I am happy to discuss the things that I have expertise about, and I'm always on the side of the patient and wanting to make life better for our patients. And that's the side I'm on.Kristin Flanary (33:25):I think also he never comes out and explicitly touches on certain topics, but it's not hard to tell where he falls.Will Flanary (33:34):If you really want read into it all.Kristin Flanary (33:38):It's not like it's a big secret.Eric Topol (33:40):I thought that too. I'm glad you mentioned it, Kristin. But it doesn't come out wide open. But yeah, it's inferred for sure.Eric Topol (33:49):I think the point being there is that because you have a reach, I think there's no reach that it has 4 million plus people by your posts and no less the tours and keynotes and everything else. So you could go anywhere but sticking to where you're well grounded, it makes a lot of sense. And anyway, I am going to be staying tuned. This is our two-year checkup. I'm hoping you're going to come to San Diego on your next tour.Kristin Flanary (34:21):We're working on 2025 plans.Will Flanary (34:23):Oh, we got more shows coming up. And we'll hit up other parts of the country too.Eric Topol (34:28):I feel like I got to meet you in person, give you a hug or something. I just feel like I'm missing out there. But it's just a joy to have had a chance to work with you on your podcast. And thanks for coming back on one of mine. There's lots of podcasts out there, but having you and joining you is such fun. So thank you.Will Flanary (34:54):This has been great. Thank you for having us.Kristin Flanary (34:55):Yeah, thank you.*****************************************Thank you for reading, listening and and subscribing to Ground Truths.If you found this fun and informative please share it! Yes, laughter is the best medicine.All content on Ground Truths—its newsletters, analyses, and podcasts, are free, open-access.Paid subscriptions are voluntary. All proceeds from them go to support Scripps Research. Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years.Thanks to my producer Jessica Nguyen and to Sinjun Balabanoff for audio and video support at Scripps Research.Note on Exodus from X/twitter:Many of you have abandoned the X platform for reasons that I understand. While I intend to continue to post there because of its reach to the biomedical community, I will post anything material here in the Notes section of Ground Truths on a daily basis and cover important topics in the newsletter/analyses. Get full access to Ground Truths at erictopol.substack.com/subscribe

At the 2023 American Society of Hematology (ASH) Annual Meeting in San Diego, California, Oncology Data Advisor had the privilege of speaking with many distinguished clinicians and patient advocates about their research presented at the meeting. Part 2 of this podcast series features exclusive conversations on nurse navigation to reduce socioeconomic disparities in leukemia treatment, dose reduction strategies to improve quality of life, the importance of diet in multiple myeloma, coping strategies during transplantation, and much more!

In discussion with Dr. Jens Hillengasss from Roswell Park Comprehensive Cancer Center, covering the Multiple Myeloma key practice changing/informing abstracts from American Society of Hematology (ASH) 2023 conference from Community Oncology perspective. We covered 4 important practice informing studies with Dr. Hillengass: - PERSEUS – Ph 3 Randomized Study of Dara + Bortezomib + Len + Dex (Dara-VRd) vs VRd Alone in Patients with NDMM Who Are Eligible for Autologous Stem Cell Transplantation (ASCT) - IsKia – Ph 3 Randomized Study of Isatuximab-Carfilzomib-Lenalidomide-Dexamethasone vs Carfilzomib-Lenalidomide-Dexamethasone As Pre-Transplant Induction and Post-Transplant Consolidation in NDMM - Bortezomib Dosing - Retrospective Observational Study on Real-World Bortezomib Prescribing Patterns and Outcomes in NDMM - KarMMA-3 Update - Idecabtagene Vicleucel (ide-cel) vs Standard Regimens in Patients with Triple-Class–Exposed (TCE) RRMM: Updated Analysis

Drs Joseph Mikhael and Nina Shah discuss the exciting future in multiple myeloma in which bispecifics, CELMoDs, modakafusp, and easily delivered CAR T-cell therapy all may play a role. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/964340). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources International Myeloma Foundation https://www.myeloma.org/ CAR T-Cell Therapy for Multiple Myeloma https://decisionpoint.medscape.com/oncology/viewarticle/951727 Bispecific Antibodies Versus CAR T-Cells in Multiple Myeloma Treatment: Pros and Cons https://decisionpoint.medscape.com/oncology/viewarticle/967868 Cytokine Release Syndrome https://emedicine.medscape.com/article/2500111-overview Bispecific Antibodies With Multiple Targets Moving Forward in Multiple Myeloma https://ascopost.com/issues/may-10-2022-supplement-hematologic-oncology-almanac/bispecific-antibodies-with-multiple-targets-moving-forward-in-multiple-myeloma/ Study to Evaluate the Safety and Tolerability of CC-92328 in Participants With Relapsed and/or Refractory Multiple Myeloma https://clinicaltrials.gov/ct2/show/NCT04975399 B-Cell Maturation Antigen (BCMA) in Multiple Myeloma: Rationale for Targeting and Current Therapeutic Approaches https://www.nature.com/articles/s41375-020-0734-z GPRC5D Is a Target for the Immunotherapy of Multiple Myeloma With Rationally Designed CAR T Cells https://www.science.org/doi/10.1126/scitranslmed.aau7746 Phase I Study of the Anti-FcRH5 Antibody-Drug Conjugate DFRF4539A in Relapsed or Refractory Multiple Myeloma https://www.nature.com/articles/s41408-019-0178-8 belantamab mafodotin https://reference.medscape.com/drug/blenrep-belantamab-mafodotin-4000056 idecabtagene vicleucel https://reference.medscape.com/drug/abecma-idecabtagene-vicleucel-4000133 ciltacabtagene autoleucel https://reference.medscape.com/drug/carvykti-ciltacabtagene-autoleucel-4000224 A Study of Talquetamab in Participants With Relapsed or Refractory Multiple Myeloma https://clinicaltrials.gov/ct2/show/NCT04634552 Dose-Escalation Study of Cevostamab in Participants With Relapsed or Refractory Multiple Myeloma (R/R MM) https://www.clinicaltrials.gov/ct2/show/NCT03275103 Molecular Mechanisms of Cereblon-Interacting Small Molecules in Multiple Myeloma Therapy https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623651/ Open-Label Study Comparing Iberdomide, Daratumumab and Dexamethasone (IberDd) Versus Daratumumab, Bortezomib, and Dexamethasone (DVd) in Participants With Relapsed or Refractory Multiple Myeloma (RRMM) (EXCALIBER-RRMM) https://clinicaltrials.gov/ct2/show/NCT04975997 Modakafusp Alfa (TAK-573), an Immunocytokine, Shows Clinical Activity in Patients with Relapsed/Refractory Multiple Myeloma; Updated Results from a First-in-Human Phase 1 Study https://www.sciencedirect.com/science/article/pii/S0006497121028858 A Phase I Study of MCARH109 and MCARH125 CAR T-Cell Therapy in People With Multiple Myeloma https://www.mskcc.org/cancer-care/clinical-trials/22-052

Joseph Mikhael, MD, and Saad Usmani, MD, discuss options in managing triple-class refractory multiple myeloma including selinexor, belantamab mafodotin, and CAR T-cell therapy. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/964339). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Multiple Myeloma https://emedicine.medscape.com/article/204369-overview Selinexor Prescribing Information https://www.karyopharm.com/wp-content/uploads/2019/07/NDA-212306-SN-0071-Prescribing-Information-01July2019.pdf Belantamab Mafodotin Prescribing Information https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Blenrep/pdf/BLENREP-PI-MG.PDF Cytokine Release Syndrome https://emedicine.medscape.com/article/2500111-overview Trending Clinical Topic: CAR T-cell Therapy https://reference.medscape.com/viewarticle/965011 Consensus Recommendations for the Clinical Management of Patients With Multiple Myeloma Treated With Selinexor https://www.karyopharm.com/wp-content/uploads/2020/06/Consensus-Recommendations_June2020.pdf Selinexor, Bortezomib and Dexamethasone: An Effective Salvage Regimen for Heavily Pretreated Myeloma Patients https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8932935/ Once Weekly Selinexor, Carfilzomib, and Dexamethasone (XKd) in Carfilzomib Nonrefractory Multiple Myeloma (MM) Patients. https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.8038 Ide-cel Prescribing Information https://packageinserts.bms.com/pi/pi_abecma.pdf Belantamab Mafodotin for Relapsed or Refractory Multiple Myeloma (DREAMM-2): A Two-Arm, Randomised, Open-label, Phase 2 Study https://linkinghub.elsevier.com/retrieve/pii/S1470-2045(19)30788-0 DREAMM Trials https://dreammtrials.com/ Blenrep (Belantamab Mafodotin) REMS https://www.accessdata.fda.gov/scripts/cder/rems/index.cfm?event=IndvRemsDetails.page&REMS=403 Band Keratopathy https://emedicine.medscape.com/article/1194813-overview Cilta-cel Prescribing Information https://www.fda.gov/media/156560/download BCMA-Directed CAR T-cell Therapy in Adult Patients With Relapsed and/or Refractory Multiple Myeloma https://clinicaltrials.gov/ct2/show/NCT04318327

In this episode, Paul Richardson, MD, presents the primary results from the randomized phase 3 DETERMINATION trial, which was started in 2010. Dr Richardson speaks about the active combination of lenalidomide, bortezomib, and dexamethasone(RVd) and autologous stem cell transplantation and R maintenance to progression for patients with newly diagnosed multiple myeloma. Dr Richardson spoke on this topic at 2022 ASCO Annual Meeting in Chicago, Illinois.

Joseph Mikhael, MD, and Ashley Rosko, MD, discuss the role of comorbidities in multiple myeloma and stress the importance of shifting away from the sole use of age-based treatment decisions. Relevant disclosures can be found with the episode show notes on Medscape.com (https://www.medscape.com/viewarticle/964338). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Multiple Myeloma https://emedicine.medscape.com/article/204369-overview International Myeloma Working Group Frailty Score Calculator http://www.myelomafrailtyscorecalculator.net/ R-MCI: Myeloma Comorbidity Index https://www.myelomacomorbidityindex.org/en_calc.html A Simplified Frailty Scale Predicts Outcomes in Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma Treated in the FIRST (MM-020) Trial https://www.nature.com/articles/s41375-019-0539-0 Treatment of Multiple Myeloma: ASCO and CCO Joint Clinical Practice Guideline https://ascopubs.org/doi/full/10.1200/JCO.18.02096 Frailty in Older Adults: Evidence for a Phenotype https://academic.oup.com/biomedgerontology/article/56/3/M146/545770 Comprehensive Geriatric Assessment https://www.uptodate.com/contents/comprehensive-geriatric-assessment Carfilzomib or Bortezomib in Combination With Lenalidomide and Dexamethasone for Patients With Newly Diagnosed Multiple Myeloma Without Intention for Immediate Autologous Stem-Cell Transplantation (ENDURANCE): A Multicentre, Open-Label, Phase 3, Randomised, Controlled Trial https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591827/

Multiple myeloma is a rare form of cancer affecting the places that bone marrow is active in an adult.  A diagnosis of Stage 3B multiple myeloma cost Victor Phiri the use of his left eye and reduced the field of vision in his right eye.  After he went into remission, osteolytic lesions were discovered in his left humerus bone, which limits the function of his arm.  Thanks to his faith and the support of friends and family, Victor maintains a positive attitude and continues to work as a pharmacist in Lusaka, Zambia.

Joseph Mikhael, MD, and Peter Voorhees, MD, discuss frontline therapy for multiple myeloma and new options for both transplant-eligible and transplant-ineligible patients. Relevant disclosures can be found with the episode show notes on Medscape.com (https://www.medscape.com/viewarticle/964337). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources International Myeloma Foundation https://www.myeloma.org/ Lenalidomide, Bortezomib, and Dexamethasone (RVD) Regimen for Multiple Myeloma https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278911/pdf/i0018-5787-52-1-27.pdf Carfilzomib, Lenalidomide, and Dexamethasone Plus Transplant in Newly Diagnosed Multiple Myeloma https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714092/ Maintenance With Daratumumab or Observation Following Treatment With Bortezomib, Thalidomide, and Dexamethasone With or Without Daratumumab and Autologous Stem-Cell Transplant in Patients With Newly Diagnosed Multiple Myeloma (CASSIOPEIA): An Open-Label, Randomised, Phase 3 Trial https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(21)00428-9/fulltext Daratumumab, Lenalidomide, Bortezomib, and Dexamethasone for Transplant-Eligible Newly Diagnosed Multiple Myeloma: The GRIFFIN Trial https://ashpublications.org/blood/article/136/8/936/454474/Daratumumab-lenalidomide-bortezomib-and Daratumumab (DARA) Plus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Patients (Pts) with Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM): Updated Analysis of GRIFFIN After 24 Months of Maintenance https://ash.confex.com/ash/2021/webprogram/Paper149024.html Venetoclax or Placebo in Combination With Bortezomib and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma (BELLINI): A Randomised, Double-Blind, Multicentre, Phase 3 Trial https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30525-8/fulltext Addition of Isatuximab to Lenalidomide, Bortezomib and Dexamethasone As Induction Therapy for Newly-Diagnosed, Transplant-Eligible Multiple Myeloma Patients: The Phase III GMMG-HD7 Trial https://ash.confex.com/ash/2021/webprogram/Paper145097.html Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone With Minimal Residual Disease Response-Adapted Therapy in Newly Diagnosed Multiple Myeloma https://ascopubs.org/doi/10.1200/JCO.21.01935 Carfilzomib or Bortezomib in Combination With Lenalidomide and Dexamethasone for Patients With Newly Diagnosed Multiple Myeloma Without Intention for Immediate Autologous Stem-Cell Transplantation (ENDURANCE): A Multicentre, Open-Label, Phase 3, Randomised, Controlled Trial https://www.thelancet.com/article/S1470-2045(20)30452-6/fulltext Safety and Effectiveness of Weekly Carfilzomib, Lenalidomide, Dexamethasone, and Daratumumab Combination Therapy for Patients With Newly Diagnosed Multiple Myeloma The MANHATTAN Nonrandomized Clinical Trial https://jamanetwork.com/journals/jamaoncology/fullarticle/2778195 Carfilzomib or Bortezomib in Relapsed or Refractory Multiple Myeloma (ENDEAVOR): An Interim Overall Survival Analysis of an Open-Label, Randomised, Phase 3 Trial https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30578-8/fulltext Carfilzomib With Cyclophosphamide and Dexamethasone or Lenalidomide and Dexamethasone Plus Autologous Transplantation or Carfilzomib Plus Lenalidomide and Dexamethasone, Followed by Maintenance With Carfilzomib Plus Lenalidomide or Lenalidomide Alone for Patients With Newly Diagnosed Multiple Myeloma (FORTE): A Randomised, Open-Label, Phase 2 Trial https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(21)00535-0/fulltext Lenalidomide, Bortezomib, and Dexamethasone With Transplantation for Myeloma https://www.nejm.org/doi/full/10.1056/NEJMoa1611750

In this podcast episode,Charise Gleason, MSN, NP-BC, AOCNP, discusses clinical considerations for patients with multiple myeloma after relapse on initial therapy. Topics in this podcast include:Strategies for monitoring for disease progressionDisease, therapy, and patient considerations for treatment selection at first relapseNursing implications and supportive care considerations for patients receiving therapy for relapsed diseasePresenter:Charise Gleason, MSN, NP-BC, AOCNPAdvanced Practice Provider ChiefWinship Cancer InstituteAdjunct FacultyNell Hodgson Woodruff School of NursingEmory UniversityAtlanta, GeorgiaCE/AAPA credit available by visiting the online program: https://bit.ly/3ee9IvsLink to full program, including downloadable slidesets:https://bit.ly/3ee9Ivs

In this podcast episode, Beth Faiman, PhD, MSN, APRN-BC, AOCN, discusses clinical considerations for diagnosis and optimal treatment selection for initial management of patients with multiple myeloma. Topics in this podcast include:IMWG criteria for diagnosing smoldering and active myelomaRisk stratification of smoldering myeloma with 2/20/20 criteria and active myeloma with R-ISS stagingIndividualizing initial treatment for ASCT-ineligible myelomaSelecting optimal initial treatment for ASCT-eligible myelomaPresenter: Beth Faiman, PhD, MSN, APRN-BC, AOCNNurse PractitionerCleveland Clinic Taussig Cancer InstituteCleveland, OhioCE/AAPA credit available by visiting the online program: https://bit.ly/3ee9IvsLink to full program, including downloadable slidesets: https://bit.ly/3ee9Ivs

In this podcast episode, Suzanne Lentzsch, MD, PhD, and  Saad Z. Usmani, MD, MBA, FACP, discuss how they select optimal treatment for relapsed/refractory (R/R) multiple myeloma (MM) and answer audience questions from a live webinar. Topics include:Selecting optimal triplet regimen after first relapseSequencing treatment options after multiple relapsesManaging patient expectations when selecting treatmentsEmerging treatment options for R/R MMPresenters:  Suzanne Lentzsch, MD, PhDDirector, Multiple Myeloma and Amyloidosis ProgramProfessor of MedicineDivision of Hematology/OncologyColumbia University Medical CenterNew York, New YorkSaad Z. Usmani, MD, MBA, FACPClinical Professor of MedicineDepartment of Hematologic Oncology & Blood DisordersDivision ChiefPlasma Cell Disorders DivisionLevine Cancer Institute/Atrium HealthCharlotte, North CarolinaSupported by educational grants from Amgen; Bristol-Myers Squibb; Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC; and Oncopeptides.Link to full program, including an downloadable slidesets and an on-demand webcast:https://bit.ly/3gjr62p

In this episode,  Shaji K. Kumar, MD; Thomas G. Martin, MD; Philippe Moreau, MD; S. Vincent Rajkumar, MD, and Jesús F. San-Miguel, MD, PhD, answer audience questions from a recent Clinical Care Options live webinar on managing multiple myeloma. Topics include:Approaches for managing smoldering multiple myelomaInsights on new strategies for managing newly diagnosed multiple myelomaIncorporating newly approved agents in the frontline and early relapse settingChoosing and sequencing BCMA-targeted therapiesManaging patients with refractory multiple myelomaPresenters:Shaji K. Kumar, MDMark and Judy Mullins Professor of Hematological MalignanciesChair, Myeloma Amyloidosis Dysproteinemia GroupConsultant, Division of HematologyMayo ClinicRochester, MinnesotaThomas G. Martin, MDClinical Professor of MedicineAssociate Director, Myeloma ProgramUniversity of California, San Francisco Medical CenterSan Francisco, CaliforniaPhilippe Moreau, MDProfessor of Clinical HematologyHead, Hematology DepartmentUniversity Hospital Hôtel-DieuNantes, FranceS. Vincent Rajkumar, MDEdward W. and Betty Knight Scripps Professor of MedicineMayo ClinicRochester, MinnesotaJesús F. San-Miguel, MD, PhDDirector of Clinical and Translational MedicineUniversidad de NavarraPamplona, SpainSupported by educational grants from Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Karyopharm and Oncopeptides.Link to full program, including downloadable slidesets and expert commentaries:https://bit.ly/39MWNid 

Featuring an interview with Dr Natalie S Callander, including the following topics: Treatment of high-risk smoldering multiple myeloma (MM) with carfilzomib, lenalidomide and dexamethasone followed by maintenance lenalidomide: A Phase II clinical and correlative study (0:00) Early versus late autologous stem cell transplant for newly diagnosed MM: Long-term follow-up analysis of the IFM 2009 trial (3:27) Updated analysis of the GRIFFIN trial: Daratumumab with lenalidomide, bortezomib and dexamethasone for patients with transplant-eligible newly diagnosed MM (14:48) Results from the ANDROMEDA trial evaluating bortezomib, cyclophosphamide and dexamethasone with or without daratumumab for newly diagnosed amyloid light chain (AL) amyloidosis (17:20) Interim analysis of the IKEMA trial evaluating depth of response and response kinetics with isatuximab added to carfilzomib and dexamethasone for relapsed/refractory (R/R) MM (21:23) KarMMa trial: Efficacy and safety of idecabtagene vicleucel in elderly patients with R/R MM (27:55) CARTITUDE-1: Phase Ib/II study of ciltacabtagene autoleucel, a B-cell maturation antigen-directed CAR (chimeric antigen receptor) T-cell therapy, for R/R MM (37:21) Activity and safety of the bispecific antibodies talquetamab and cevostamab (BFCR4350A) in patients with R/R MM (42:21) ANCHOR trial: Updated efficacy and safety of melflufen with either dexamethasone/daratumumab or dexamethasone/bortezomib for R/R MM (47:25) Iberdomide in combination with dexamethasone, daratumumab or both and with dexamethasone/bortezomib for patients with R/R MM (52:39) ALGONQUIN trial: Efficacy and tolerability of belantamab mafodotin with pomalidomide/dexamethasone for patients with R/R MM (55:33) Selinexor in combination with pomalidomide and dexamethasone for R/R MM (57:29) Phase II SWOG-S1702 study of isatuximab for patients with previously treated AL amyloidosis (1:00:17) Safety and efficacy of CAEL-101 in patients with AL amyloidosis on a Phase II dose selection study (1:02:02) Five-year follow-up of ibrutinib with rituximab for Waldenström macroglobulinemia (WM): Final analysis from the Phase III iNNOVATETM study (1:04:06) Bortezomib in combination with dexamethasone, rituximab and cyclophosphamide as first-line treatment for WM: Results of a randomized Phase II trial (1:07:11) Roles of zanubrutinib and acalabrutinib for WM (1:09:40) CME information and select publications

FDA 批准治疗慢性免疫性血小板减少症的新药BMJ 术后血栓预防中，加压袜并不能提供额外的获益Nature子刊 白血病治疗性疫苗的研制阿凡波帕（avatrombopag）阿凡波帕（avatrombopag）血小板生成素受体激动剂。在上周三《消化科星期三 Episode 23》中已经给介绍了阿凡波帕用于治疗慢性肝病合并血小板减少患者的手术前用药，可以改善血小板计数、减少出血和输血。2019年6月，该药的适应症被扩展至慢性免疫性血小板减少。《随机对照研究：阿凡波帕治疗慢性免疫血小板减少症的3期临床研究》British Journal of Haematology，2018年11月 (1)这个安慰剂对照、多中心、随机、双盲的3阶段的研究，目的是评估阿凡波帕20mg qd治疗成人慢性、免疫性血小板减少症的疗效。研究纳入49位患者，入组时血小板计数

FDA 批准治疗慢性免疫性血小板减少症的新药BMJ 术后血栓预防中，加压袜并不能提供额外的获益Nature子刊 白血病治疗性疫苗的研制阿凡波帕（avatrombopag）阿凡波帕（avatrombopag）血小板生成素受体激动剂。在上周三《消化科星期三 Episode 23》中已经给介绍了阿凡波帕用于治疗慢性肝病合并血小板减少患者的手术前用药，可以改善血小板计数、减少出血和输血。2019年6月，该药的适应症被扩展至慢性免疫性血小板减少。《随机对照研究：阿凡波帕治疗慢性免疫血小板减少症的3期临床研究》British Journal of Haematology，2018年11月 (1)这个安慰剂对照、多中心、随机、双盲的3阶段的研究，目的是评估阿凡波帕20mg qd治疗成人慢性、免疫性血小板减少症的疗效。研究纳入49位患者，入组时血小板计数

FDA 批准新药治疗β地中海贫血和骨髓增生异常综合征导致的贫血Blood 新的评分系统用以预测镰状细胞病患者、造血细胞移植治疗的预后NEJM 一周一次的Ⅷ因子替代疗法治疗血友病卢斯帕塞普（Luspatercept）卢斯帕塞普（Luspatercept）是一种重组融合蛋白，可以选择性结合转化生长因子β超家族配体，可促进红细胞成熟。2019年11月，卢斯帕塞普（Luspatercept）被FDA批准用于治疗β地中海贫血；2020年4月被FDA批准用于治疗低危骨髓增生异常综合征导致的贫血。《BELIEVE研究：卢斯帕塞普用于治疗输血依赖型β地中海贫血的3期临床研究》New England Journal of Medicine，2020年3月 (1)研究的目的是评价卢斯帕塞普治疗输血依赖型β地中海贫血患者的疗效和安全性。研究纳入224名、输血依赖型β-地中海贫血成年患者，在最佳支持性治疗基础上，随机接受卢斯帕塞普（1.00-1.25mg/kg）或安慰剂，中位治疗时间64周。在第13周-24周期间，与基线相比，卢斯帕塞普组的输血负担减少≥33%、且输血量减少≥2个单位的患者比例明显高于安慰剂组（21.4% vs 4.5%）。在任意12周的间隔期内，卢斯帕塞普组中，输血负担减少≥33%的患者比例高于安慰剂组（70.5% vs 29.5%），而输血负担减少≥50%的患者比例也高于安慰剂组(40.2% vs 6.3%）。第48周，两组间血清铁蛋白水平的最小二乘法平均差为-348μg/L， 卢斯帕塞普治疗组更佳。与安慰剂相比，卢斯帕塞普组更易出现短暂性骨痛、关节痛、头晕、高血压和高尿酸血症等不良事件。 结论：卢斯帕塞普可减少输血依赖型β地中海贫血患者的输血负担，且安全性良好。《MEDALIST研究：卢斯帕塞普治疗低风险骨髓异常增生综合征患者的3期临床研究》New England Journal of Medicine，2020年1月 (2)这个双盲、安慰剂对照的3期试验中，纳入中低风险的、骨髓增生异常综合症、伴有环形铁幼粒细胞、对促红素不敏感或不耐受、需规律输血的患者，一共229人，随机接受卢斯帕塞普（1.75mg/kg ip q3w）或安慰剂。卢斯帕塞普组和安慰剂组中，连续≥8周无需输血的患者比例分别为38%和13% （P

FDA 批准新药治疗β地中海贫血和骨髓增生异常综合征导致的贫血Blood 新的评分系统用以预测镰状细胞病患者、造血细胞移植治疗的预后NEJM 一周一次的Ⅷ因子替代疗法治疗血友病卢斯帕塞普（Luspatercept）卢斯帕塞普（Luspatercept）是一种重组融合蛋白，可以选择性结合转化生长因子β超家族配体，可促进红细胞成熟。2019年11月，卢斯帕塞普（Luspatercept）被FDA批准用于治疗β地中海贫血；2020年4月被FDA批准用于治疗低危骨髓增生异常综合征导致的贫血。《BELIEVE研究：卢斯帕塞普用于治疗输血依赖型β地中海贫血的3期临床研究》New England Journal of Medicine，2020年3月 (1)研究的目的是评价卢斯帕塞普治疗输血依赖型β地中海贫血患者的疗效和安全性。研究纳入224名、输血依赖型β-地中海贫血成年患者，在最佳支持性治疗基础上，随机接受卢斯帕塞普（1.00-1.25mg/kg）或安慰剂，中位治疗时间64周。在第13周-24周期间，与基线相比，卢斯帕塞普组的输血负担减少≥33%、且输血量减少≥2个单位的患者比例明显高于安慰剂组（21.4% vs 4.5%）。在任意12周的间隔期内，卢斯帕塞普组中，输血负担减少≥33%的患者比例高于安慰剂组（70.5% vs 29.5%），而输血负担减少≥50%的患者比例也高于安慰剂组(40.2% vs 6.3%）。第48周，两组间血清铁蛋白水平的最小二乘法平均差为-348μg/L， 卢斯帕塞普治疗组更佳。与安慰剂相比，卢斯帕塞普组更易出现短暂性骨痛、关节痛、头晕、高血压和高尿酸血症等不良事件。 结论：卢斯帕塞普可减少输血依赖型β地中海贫血患者的输血负担，且安全性良好。《MEDALIST研究：卢斯帕塞普治疗低风险骨髓异常增生综合征患者的3期临床研究》New England Journal of Medicine，2020年1月 (2)这个双盲、安慰剂对照的3期试验中，纳入中低风险的、骨髓增生异常综合症、伴有环形铁幼粒细胞、对促红素不敏感或不耐受、需规律输血的患者，一共229人，随机接受卢斯帕塞普（1.75mg/kg ip q3w）或安慰剂。卢斯帕塞普组和安慰剂组中，连续≥8周无需输血的患者比例分别为38%和13% （P

In this episode, Jesús F. San-Miguel, MD, PhD; Paula Rodriguez-Otero, MD, PhD; and  Prof. Dr. med. Katja Weisel answer questions focused on current and emerging therapies for early and late relapsed, refractory multiple myeloma, with topics including:• Responses across different subgroups treated with idecabtagene vicleucel in the KarMMa trial • Selecting therapy for a patient with lenalidomide-refractory disease at first relapse• How CAR T-cell therapy, melflufen, and selinexor will fit into existing and future treatment algorithms• Key findings from the DREAMM2 trial on belantamab mafodotin• Monitoring and management strategies for ocular toxicity with belantamab mafodotinPresenters:Jesús F. San-Miguel, MD, PhDDirector of Clinical and Translational MedicineUniversidad de NavarraPamplona, SpainPaula Rodriguez-Otero, MD, PhDAssociate ProfessorConsultant in HematologyDepartment of Hematology, Clínica Universidad de NavarraUniversity of NavarraPamplona, SpainProf. Dr. med. Katja Weisel  Deputy DirectorII. Medical Clinic and PolyclinicDepartment of Oncology and HematologyDepartment of Pneumology and Bone Marrow TransplantationUniversity Medical Center  Hamburg-EppendorfHamburg, GermanyContent based on an online CME program supported by an educational grant from GlaxoSmithKline.Link to full program, including associated downloadable slidesets: https://bit.ly/2QRqYuC 

David Fajgenbaum, MD, of the University of Pennsylvania, Philadelphia, is a pioneer in the research of Castleman disease and he’s a patient himself. He joins Blood & Cancer host David Henry, MD, of Pennsylvania Hospital, Philadelphia, to talk about the presentation of Castleman, available treatments, and his own patient journey. Plus, in Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, talks about compassion fatigue among friends and family of cancer patients. This Week in Oncology Time Stamps: This week in Oncology (03:51) Interview (07:24) Clinical Correlation (34:15) Show notes Castleman disease is a group of disorders unified by certain histologic features, including: Atrophic (B-cell depleted) germinal centers with wide mantle zones. Increased number of plasma cells in the interfollicular space. Increased number of blood vessels in the interfollicular space. The disease can be subdivided into unicentric Castleman disease (UCD) or multicentric Castleman disease (MCD), based upon the extent of the lymph node involvement. Multicentric Castleman is further subdivided into HHV8-associated and non HHV8-associated (idiopathic) disease. Determination of HHV-8 status is very important for the selection of the appropriate therapeutic strategy. The presentation of Castleman Disease may be similar to the presentation of lymphomas, including fatigue, night sweats, peripheral edema, pancytopenia, and disseminated lymphadenopathy. The diagnosis depends on the unique histologic appearance after bone marrow biopsy is performed. Patients with Castleman disease often require hospitalization given rapid progression of symptoms due to massive cytokine release. MCD is a rare clinical entity, and to date, only one randomized controlled trial has been published to date (involving siltuximab). Therapeutic options: Unicentric Castleman disease Effectively treated with surgical excision of enlarged lymph node. Multicentric Castleman disease Rituximab (anti-CD20 monoclonal antibody) Has been used off-label as first-line treatment in HIV-positive/HHV-8-positive MCD, alone or in combination with conventional chemotherapeutics. Siltuximab (anti-IL-6 monoclonal antibody) Currently the only approved treatment of idiopathic MCD in the United States. Tocilizumab (humanized IL-6 receptor antagonist) Approved for treatment of idiopathic MCD in Japan. Sirolimus (mTOR pathway inhibition) Under investigation at the University of Pennsylvania for treatment of patients who have been refractory to IL-6 blockade. Bortezomib (selective proteasome inhibitor) and Anakinra (IL-1 receptor antagonist) A small number of case reports suggest these may be used in MCD.   Dr. Fajgenbaum can be reached at davidfa@pennmedicine.upenn.edu. More information about Castleman disease can be found at www.cdcn.org.  Dr. Fajgenbaum’s memoir is Chasing My Cure: A Doctor’s Race to Turn Hope into Action Show notes by Sugandha Landy, MD, resident in the department of internal medicine, University of Pennsylvania, Philadelphia.   For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc Ilana Yurkiewicz on Twitter: @ilanayurkiewicz    

Multiple Myeloma Update — Part 1: Our interview with Dr Rajkumar highlights the following topics as well as cases from his practice: Updated risk-stratification model for smoldering multiple myeloma (MM) incorporating the revised International Myeloma Working Group diagnostic criteria; therapeutic approach for standard- versus high-risk smoldering MM (00:00) Subcutaneous versus intravenous daratumumab administration for MM (05:28) Efficacy and tolerability of the recently FDA-approved regimen of daratumumab in combination with lenalidomide and dexamethasone for patients with previously untreated MM not eligible for autologous stem cell transplantation (ASCT) (06:52) Activity, tolerability and ongoing trials of carfilzomib- and bortezomib-based triplet regimens for newly diagnosed MM (08:55) Results of the Phase III CASSIOPEIA study: Bortezomib/thalidomide/dexamethasone with or without daratumumab for patients with newly diagnosed MM eligible for ASCT (12:39) Case: A man in his early 80s with MM initially treated with lenalidomide/bortezomib/dexamethasone and maintenance lenalidomide experiences relapse 2 years later (15:02) Benefits and risks of the Bcl-2 inhibitor venetoclax in combination with bortezomib/dexamethasone for relapsed/refractory (R/R) MM with and without the t(11;14) translocation on the Phase III BELLINI trial (16:43) Proposed mechanism of venetoclax-associated mortality in MM (19:35) Understanding the clinical role and limitations of surrogate endpoints for overall survival (24:29) Perspective on the possible design flaws in the BELLINI trial (28:08) CME information and select publications  

This week we cover three papers -- "Postpublication Metrics of Randomized Clinical Trials With and Without Null Findings" by Murray et al. in JAMA, "Association of Primary Care Clinic Appointment Time With Clinician Ordering and Patient Completion of Breast and Colorectal Cancer Screening" by Hsiang et al. in JAMA Network Open, and "Exceptional responders with invasive mucinous adenocarcinomas: a phase 2 trial of bortezomib in patients with KRAS G12D-mutant lung cancers" by Drilon et al. in Molecular Case Studies. We end with an interview with Dr. Christopher Booth of Queens University in Kingston, Ontario, conducted in the Plenary Session Mobile Command Unit. Postpublication Metrics: doi.org/10.1001/jama.2019.2994 PCP Appointment Time: doi.org/10.1001/jamanetworkopen.2019.3403 Exceptional Responders: doi.org/10.1101/mcs.a003665 Back us on Patreon! www.patreon.com/plenarysession

Onderzoek naar heat shock factor 1 (HSF1)-expressie bij kinderen met acute myeloïde leukemie (AML) liet zien dat de patiëntengroep met lage HSF1-expressie meer baat hebben bij behandeling met bortezomib. Fieke Hoff, MD, UMC Groningen licht de resultaten in deze video toe. Referentie1. Hoff FW, et al. ASH 2018; abstr 293.

Dr. Jacob Laubach discusses bortezomib as an alternate strategy to lenalidomide for maintenance therapy in patients with multiple myeloma.

Listen as Dr. Carol Ann Huff discusses how to dose daratumumab, bortezomib and dexamethasone in the combination regimen.

Dr Lentzsch speaks with ecancer at the 16th International Myeloma Workshop about the CASTOR trial. The CASTOR trial is a phase III randomised controlled study of daratumumab, bortezomib, and dexamethasone (DVd) versus bortezomib and dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma.

Dr Weisel speaks with ecancer at EHA 2017 about the trial of daratumumab in triplet combinations against standard of care for relapsed/refractory multiple myeloma. After an extended followup, Dr Weisel report s a mPFS of 16.7 months compared to 7.1 months. Patients with only 1 prior treatment were among the best responders, and Dr Weisel notes the recent EMA approval of this combination as a possible course of care for any suitable patients.

The use of novel agents bortezomib, lenalidomide and thalidomide in Asian patients is discussed. Bortezomib is used as induction therapy and lenalidomide and thalidomide are reserved for relapsed or refractory patients in Japan. Rare reports of complications with these agents have been reported, However these are not believed to be treatment related. The increased incidence of cancer in survivors of the atomic bomb during World War II has been addressed at IMW. Results from the Life Span Study investigating radiation effects on leukaemia, lymphoma and MM incidence in atomic bomb survivors were presented at this year's IMW meeting. This study found that the radiation exposure associated with this may be a possible predisposing factor for MGUS. However, the incidence of multiple myeloma appears to be the same as Western populations. Overall, the incidence of MM appears to be lower in the Asian population, but higher rates have been noted in Vietnamese patients. A number of clinical studies are ongoing covering the use of novel therapies, autologous stem cell transplant and maintenance therapy.

Consolidation therapy is short term and intended to further enhance the frequency and quality of response obtained with the previous treatment phases. In the era of novel agents, consolidation therapy is needed to increase the rate of complete response (CR), even in the transplant setting. Maintenance therapy is a developing concept and is one that is considered to be important in the management of minimal residual disease. A recent meta-analysis of data from the MRC Myeloma IX Study has shown that there was an improvement in progression free survival (PFS) with thalidomide maintenance. The downside to thalidomide therapy was the impaired quality of life associated with this treatment, which resulted in discontinuation at around 7 months in most patients. Lenalidomide is a viable alternative option for maintenance due to the fact that it is an oral drug and is well tolerated. Current dosage regimens in clinical trials in Italy are 3 weeks on and 1 week off, rather than continuous therapy long term. It is well tolerated in the elderly population. It has also been investigated in younger patients following high dose treatment. In these patients it has been associated with benefits in PFS across many patient subgroups. It has also been associated with overall survival (OS). Bortezomib maintenance following autologous stem cell transplant (ASCT) has also been investigated. However, this data was limited in terms of establishing its place as a maintenance option. It has been shown to be beneficial in high risk patients, but more data is needed. In the future it is likely that consolidation and maintenance are likely to be complimentary therapy protocols in the management of multiple myeloma.

In this podcast, Attar and colleagues explore whether patients aged 60-75 who enter remission with bortezomib added to standard anthracycline plus cytarabine chemotherapy during induction can be safely treated with intermediate dose cytarabine along with dose escalating bortezomib during consolidation. This regimen was tolerated at the highest dose of bortezomib tested, 1.3 mg/m2, and further randomized studies of this regimen will be planned.

Das Mantelzell-Lymphom ist ein aggressives B-NHL, das durch die Expression des Zell-zyklus-regulierenden Proteins Cyclin D1 charakterisiert ist. Diese Expression wird in den meisten Fällen durch eine chromosomale Translokation t(11;14)(q13;q32) ausgelöst. Klinisch weist das MCL mit einem medianen Überleben von nur drei bis vier Jahren eine der schlechtesten Langzeitprognosen aller Lymphomsubtypen auf. In fortgeschrittenen Stadien kommt es zu frühzeitigen Rezidiven nach der Behandlung mit konventionellen Chemotherapeutika. Es besteht daher ein dringender Bedarf an neuen, effektiveren, mo-lekular ausgerichteten Therapieformen, die zu einer Verbesserung der Prognose und der Lebensqualität der Patienten führen. In dieser Arbeit wurde hierfür das Proliferationsverhalten und die Viabilität von sechs humanen MCL-Zelllinien nach der Behandlung mit dem mTOR-Inhibitor RAD001 und dem Purin-Nukleosid-Phosphorylase-Inhibitor Forodesin in Gegenwart von 2'-Desoxyguanosin (dGuo) untersucht. Im Vordergrund stand zum einen die Charakterisierung der Wirkung von RAD001 und Forodesin+dGuo als Monosubstanzen. Zum anderen war es auch Ziel, die Antitumorwirkung zytotoxischer Kombinationen mit etablierten Substanzen der Chemotherapie, dem Proteasom-Inhibitor Bortezomib sowie dem PKCß-Inhibitor Enzastaurin bezüglich Wachstumshemmung, Zelltod und Apoptose zu untersuchen und diese Kombinationen auf antagonistische, additive oder synergistische Interaktionen hin zu analysieren. Die behandelten Zellen wurden hierzu einem Viabilitäts-Trypanblau-Test unterzogen, der hier als Screeningverfahren diente, um die Empfindlichkeit der Zellen auf unterschiedliche Dosen in Einzel- und Kombinationstherapien zu quantifizieren. Im Anschluss wurden die Resultate mit Hilfe der Zellzyklusanalyse durch Propidiumiodid-Färbung und Apoptose-Assays verifiziert und der Wirkmechanismus der Kombinationen differenziert. Als Ergebnis dieser Arbeit erzielte der mTOR-Inhibitor RAD001 als Monosubstanz bereits in subtoxischen Konzentrationen vor allem nach 48- und 72-stündiger Expositionsdauer eine antiproliferative Wirkung auf die MCL-Zelllinien. Außerdem zeigte RAD001 bei allen in dieser Arbeit untersuchten Zelllinien eine potente Inhibition des Zellzyklus, mit einer Zunahme der G0/G1- und einer Abnahme der S-Phase. Nach 48-stündiger Behandlung mit RAD001 in Kombination mit Fludarabin, Cytarabin, Bendamustin sowie Enzastaurin und Bortezomib zeigte sich bei einer Zelllinie ein Syner-gismus, die im Viabilitäts-Trypanblau-Test besonders empfindlich auf RAD001 war. Additive Effekte konnten bei vier von fünf untersuchten MCL-Zelllinien durch die Kombination von RAD001 und Bendamustin nachgewiesen werden. Bei zwei von fünf Zelllinien konnten diese Effekte auch mit Fludarabin erzielt werden. Vier von fünf MCL-Zelllinien zeigten nach 48-stündiger Behandlung bei der Kombination von RAD001 plus Cytarabin eine antagonistische Wirkung. Die Behandlung mit der Kombination von RAD001 plus Bortezomib oder Enzastaurin führte in einigen MCL-Zelllinien ebenso zu additiven Effekten. Die Kombinationen RAD001 plus Forodesine+dGuo und RAD001 plus Bortezomib wiesen in drei von fünf MCL-Zelllinien dagegen eine antagonistische Wirkung auf. Nach der Behandlung mit Forodesin unter Beigabe von dGuo konnte ebenfalls eine anti-proliferative Wirkung in allen untersuchten MCL-Zelllinien induziert werden. Die weiteren Untersuchungen mithilfe von Zellzyklus- und Apoptose-Analysen zeigten jedoch keine wesentlichen Veränderungen im Vergleich zu der jeweiligen unbehandelten Kontrolle. Ganz anders stellte sich die Zellzyklus-Analyse der T-ALL-Kontrollzelllinie Jurkat dar. Hier zeigte sich eine deutliche T-Zelllinien-spezifische Wirkung des PNP-Inhibitors Forodesin unter Zugabe von 2'-Desoxyguanosin. Die Kombination von Forodesin+dGuo und Bendamustin wies bei vier von fünf MCL-Zelllinien nach 72 Stunden Expositionszeit ebenso eine additive Wirkung auf. Ein synergistischer Effekt war nach 48 Stunden dagegen lediglich bei einer MCL-Zelllinie zu erkennen. Die Kombination von Forodesin und Fludarabin zeigte schließlich nach 72 Stunden Expositionszeit bei vier MCL-Zelllinien und der T-ALL-Zelllinie Jurkat eine antagonistische Wirkung, was letztendlich auf das Konkurrieren der Phosphorylierung von dGuo und Fludarabin zurückzuführen ist. Bei vier von fünf untersuchten MCL-Zelllinien wies die Kombination von Forodesin+dGuo und Bortezomib ebenfalls eine antagonistische Wirkung auf, da die beiden Kombinationspartner um DNA-Bindungsstellen konkurrieren. Eine additive Wirkung ließ sich am Ende auch bei drei von fünf MCL-Zelllinien mit der Kombination von Forodesin+dGuo plus Enzastaurin nachweisen. Zusammenfassend wäre somit ein Einsatz des mTOR-Inhibitors RAD001 und des Purin-Nukleosid-Phosphorylase-Hemmstoffs Forodesin in Gegenwart von 2’-Desoxyguanosin additiv zu anderen Chemotherapeutika im Rahmen der Mantelzell-Lymphom-Therapie durchaus vielversprechend. Allerdings sind bei der Entwicklung dieser und weiterer, in-novativer Kombinationen die zugrundeliegenden molekularen Mechanismen zu beachten, um mögliche antagonistische Wirkungen zu vermeiden.

This podcast will provide a critical evaluation of the combination of bortezomib, thalidomide, and dexamethasone in relapsed multiple myeloma

Thu, 1 Mar 2012 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/14232/ https://edoc.ub.uni-muenchen.de/14232/1/Lorenz_Monika.pdf Lorenz, Monika ddc:610, ddc:600, Medizinische Fakultät

Das Mantelzelllymphom (MCL) ist eine neoplastische Erkrankung des blutbildenden Systems, die durch die ektopische Expression des Zellzyklus-regulierenden Proteins Cyclin D1 charakterisiert ist und im Regelfall durch eine chromosomale Translokation t(11;14)(q13;q32) ausgelöst wird. Trotz stetiger Verbesserungen der Behandlungsmethoden, insbesondere der Optimierung der Kombinationstherapie und dem Einsatz der Anti-CD20-Antikörpertherapie- konnte bislang jedoch keine wesentliche Verbesserung des Gesamtüberlebens erzielt werden. Die Untersuchung der Wirksamkeit und der Wirkmechanismen neuer, molekular ausgerichteter Therapieformen hat daher bei dieser Erkrankung besonders große Bedeutung. Zu diesem Zweck wurde ein 2D-PAGE-basiertes Verfahren zur Analyse der zellulären Proteinspiegel etabliert und durch die Charakterisierung der Unterschiede zwischen zwei Non-Hodgkin-Lymphom (NHL)-Subtypen (MCL und FL) auf Proteomebene validiert. Im Verlauf dieser Tests wurde darüber hinaus die Aussagekraft der 2D-PAGE-Analyse durch die Verwendung von „Proben-Pools“ verbessert, wodurch die Detektion zufallsbedingter molekularer „Bystander“-Aberrationen unterdrückt und ein repräsentativer molekularer Phänotyp charakterisiert werden konnte. Die Zahl solcher unspezifischen Proteinpunkte, die nur in einzelnen Zelllinien des Probenkollektivs nachgewiesen wurden, konnten in den „Proben-Pools“ um >66% gesenkt werden. Im Vergleich der zellulären Proteinspiegel der beiden NHL-Subtypen wiesen 175 von insgesamt 1350 Punkte auf den 2D-PAGE-Gelen Subtyp-spezifisch unterschiedliche Proteinspiegel auf, von denen 38 Punkte durch Massenspektrometrie (MS) identifiziert wurden. Die identifizierten Kandidatenproteine können grob 7 funktionellen Gruppen (Apoptose / Zelltod, Reparaturmechanismen, Zellzyklus und Proliferation, Regulation der Transkription, grundlegende zelluläre Funktionen, Tumor-Antigene, unbekannte Proteinfunktion / hypothetische Proteine)zugeordnet werden und interagieren vorwiegend in einem Netzwerk um den Tumorsuppressor p53. Das Verfahren der 2D-PAGE-Analyse mit massenspektrometrischer (MS) Proteinidentifizierung wurde anschließend benutzt, um die molekulare Wirkung des Proteasomen-Inhibitors Bortezomib auf MCL (Zelllinien und primäre Patientenzellen) zu analysieren. Dazu wurden 5 MCL-Zelllinien (Granta519, HBL-2, Jeko-1, NCEB-1 und Rec-1) einer Bortezomib-Konzentration von 25nM ausgesetzt und die Veränderungen der zellulären Proteinspiegel nach 1h und 4h mit denen von unbehandelten Zellen verglichen. In dieser Analyse waren die Proteinspiegel von 148 der insgesamt 1013 in allen MCL-Zelllinien nachweisbaren Proteinpunkten nach Bortezomib signifikant verändert. Durch MS konnten 38 der 41 reproduzierbar nachweisbaren Proteinpunkte identifiziert werden, wobei 20 ausschließlich in Bortezomib-sensitiven Zelllinien veränderte Spiegel aufwiesen. Eine Western Blot-Analyse von 17 der 38 identifizierten Proteine bestätigte in 76% die in 2D-PAGE-Gelen beobachteten Veränderungen der Proteinspiegel. Alle Zelllinien zeigten veränderte Spiegel von verschiedenen Hitzeschockproteinen (HSPA9, HSP7C, HSPA5, HSPD1), während Zelllinien die auf eine Behandlung mit Bortezomib ansprachen, auch veränderte Proteinspiegel bei Parametern des Energiestoff-wechsels (ATP5B, AK5, TPI1, ENO2, ENO3, ALDOC, GAPDH), der RNA- und Transkriptionsregulation (HNRPL, SFRS12) und der Zellteilung (NEBL, ACTB, SMC1A, C20orf23) sowie der Tumorsuppressoren ENO-1 und FH aufwiesen. Diese Proteine konnten in einem engen Interaktionsnetzwerk um das wichtige zelluläre „Checkpoint“-Molekül p53 gruppiert werden. Entsprechend konnten diese Ergebnisse in primären MCL-Patientenproben bestätigt werden, was die Rolle dieser Proteine im Rahmen der Proteasomeninhibition beim MCL unterstreicht.

Audio Journal of Oncology, February 26th, 2008 "Total Therapy" Possible Cure For Multiple Myeloma? BART BARLOGIE, University of Arkansas, Little Rock REFERENCE: 4th European Congress on Hematologic Malignancies, Paris 22-24 February, 2008 A treatment known as "total therapy" could cure many patients with multiple myeloma, conference-goers have just heard. The targeted drugs thalidomide and bortezomib, coupled with tandem autologous transplants, are used by Arkansas-based Bart Barlogie. In Paris he told Peter Goodwin about their success.

Audio Journal of Medicine, September 18th, 2007 Reporting from: 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), Chicago, 2007 Bortezomib for Multiple Myeloma Can Cause Reactivation of Viruses GEORG HÄRTER, University Hospital, Ulm REFERENCE: Interscience Conference on Antimicrobial Agents and Chemotherapy, 17 – 20 September 2007, Chicago For patients with multiple myeloma being treated with the proteasome inhibitor bortezomib, doctor’s should be wary of viral reactivation – and they should give antiviral prophylaxis in all cases. This finding was unveiled at ICAAC by Georg Härter from the University Hospital in Ulm, and he shared his data with Derek Thorne.