Meet The Professor: Current and Future Management of Chronic Lymphocytic Leukemia — Part 3 of a 6-Part Series (Webinar Video Proceedings)
Meet The Professor: Current and Future Management of Chronic Lymphocytic Leukemia
— Part 3 of a 6-Part Series (Webinar Video Proceedings) Kerry Rogers, MD Featuring perspectives from Dr Kerry Rogers. Published April 18, 2022.
Introduction DR LOVE: I’m Neil Love from Research To Practice and welcome to Meet The Professor, as today we talk about the current and future management of chronic lymphocytic leukemia with Dr Kerry Rogers from the Ohio State University in Columbus, Ohio. We have a great faculty for this series and later on, we’ll show you the results of a poll we did of the faculty of their usual treatment practices. As always, if you have any questions or cases you’d like to run by Dr Rogers, just type them into the chat room and we’ll talk about as many of these as we have time today. If you’re into audio programs, we know a lot of people end up listening to these webinars on replay, check out our Oncology Today podcast series, including a recent program with Dr Peter Hillmen on CLL. We do webinars all the time. I’m really looking forward to next week. We’re starting our MDS series with Dr Komrokji. We’ll see where venetoclax and HMA maybe is going to start fitting into that situation. The next day, we’ll be meeting with Dr Evens to talk about lymphomas and go back and see what’s going on after the big diffuse large B-cell papers just presented at the ASH meeting, how that’s playing out. And then, we’ll meet with Professor Claire Harrison to talk about myelofibrosis, including the recent approval of pacritinib. Really looking forward to our Year in Review program on prostate cancer after the GU Symposium with those wild PARP papers that we’re going to talk about with Dr Antonarakis. And then, we’ll come back with Dr Brown from Dana-Farber talking about CLL again. We have a huge symposium series at the ONS program starting April 27th. In 3 days, we’re going to do 10 completely different seminars. Not just for nurses, we’re going to put it out online. I hope people attend. We’re going to talk about what investigators say when they talk to their patients about new therapies and clinical trials. But today, we’re here to talk about CLL. It seems like we talk about it all the time and yet every time we talk about it, it seems different, particularly when we start getting into cases in clinical practice. So as always, we have some docs who are out there taking care of patients and are going to present very briefly some cases and questions they have about some of the patients they’re taking care of. Here's where we’re heading here today. We changed the agenda a little bit to match up with your interests, particularly in hairy cell as well as immune cytopenias. We have 2 separate sections. In module 2, we’ll get into some of the more common questions that come up in sequencing of therapy. Hairy Cell Leukemia DR LOVE: But I want to just take a step back. And I know hairy cell — actually, I think hairy cell was discovered at Ohio State. You have a Center of Excellence there. I’m really curious about that and how that works and just getting research done in such a rare cancer. But I want to, maybe you could just like we’re making rounds down the hall and say, hey, can you give us a little update on some of the things you think general medical oncologists ought to know about in terms of hairy cell, including COVID? DR ROGERS: Yeah. So I think there’s a couple things that are really important that have happened in hairy cell leukemia. As I’m sure everyone knows, it’s highly treatable, has a very good survival, and cladribine is the most commonly used agent and can result in decades of remission. The median is usually like 7 to 8 years before next treatment, but some people, of course, can get longer, but there’s still a need to improve on that. And there was a recent randomized study, it was a randomized Phase II, done at the NIH that compared standard cladribine, which is given over a very short period of time, with rituximab if disease was detected later to a novel regimen, which it’s not the standard to give rituximab delayed, but it was part of this trial, and that was compared to a new regimen that was actually concurrent rituximab with cladribine upfront. And this is as an initial treatment. What’s really interesting is just the hairy cell patients do so well that when this was reported with over 7 years of follow-up, there was still no difference in progression free survival, just because everyone did great, but the patients who received concurrent cladribine and rituximab did have less incidence of detectable hairy cells. So we think that over many years that will translate into a better outcome overall. So this is actually added to the NCCN guidelines and should be considered as an initial treatment for hairy cell leukemia. And the reason I’m bringing this up, one is just because I think this is something that should be discussed with patients, but also with the setting of the pandemic, I think there’s some important considerations for use of cladribine or this new combination of cladribine and concurrent rituximab. So there was more severe thrombocytopenia with the combination and I think you really have to think about your patient, their natural lifespan independent of the hairy cell and their fitness if you’re going to consider the combined regimen and kind of where their counts are starting out because we see severe cytopenias with cladribine if people start out with very poor marrow function or transfusion dependent and with the severe thrombocytopenia with the addition of concurrent rituximab, I really think that this combination upfront is best for fitter patients and certainly younger ones where a PFS benefit would be a huge advantage as opposed to people that might need one treatment in the rest of their natural lifespan. The other thing is more drugs always means more side effects, but particularly in the era of COVID-19, rituximab, not necessarily in hairy cell specifically but overall, has been shown to worsen outcomes with COVID-19 infection and also, of course, decreases the ability to respond to things like vaccines. And so if you’re going to add another drug that’s an antibody that has these kind of immunological effects that are disadvantageous during a pandemic, I think you really have to have a good reason to do it. So I think it’s super exciting that there’s this now concurrent rituximab and cladribine option, but I do think that people have to be very careful in selecting which patients that’s most suitable for. DR LOVE: So we’re getting a flurry of questions from the chat room about this, interestingly enough. So Susanna actually has a patient, a man with hairy cell. Got PICC, getting 7-day cladribine infusion now. Was planning to give rituximab 4 to 6 weeks later, should I? DR ROGERS: Yeah. So rituximab given after cladribine or pentostatin has been a standard in the relapsed refractory hairy cell setting for quite some time and so it sort of prolongs the time to next treatment. And so I think that should always be considered. For myself, I do think that is a benefit that you have to discuss with patients whether or not you should do that. And then you just have to take their preferences and their factors into account too. So there is, especially with COVID, a risk to giving anti-CD20. And before this pandemic, I thought about giving rituximab as something with minimal toxicity or impact, but I think now, I have a more detailed discussion about what that might mean for their immune status. And then also, you’ve just got to think like if this is a relapsed refractory patient, what was their prior remission duration? Is there need to extend that? And then, is the patient well enough to undergo the additional treatment? So I do think in fit patients, that’s very reasonable to do rituximab after cladribine, especially if it’s someone that’s been treated before. DR LOVE: She also wants to know whether you need to continue antivirals and antibiotics until the CD4 count rises. DR ROGERS: That is an excellent question that actually the hairy cell leukemia group, both at Ohio State and some of our peers at other institutions that we discuss with, would love a scientific or academic answer to. Presently, there’s no formal data on that. A lot of people have a practice to continue PJP prophylaxis until CD4 count recovers. For myself, I generally continue antiviral prophylaxis for 6 months to a year after treatment depending on which treatment they got, if they got rituximab and if they’ve had shingles before or have risk factors for viral reactivation. I actually don’t use a lot of Bactrim or PJP prophylaxis myself just because the incidence of PJP is low and people tend to get a lot of problems with the Bactrim. But a lot of people do and it’s actually very reasonable to do. And while I have no data about waiting for count recovery, it’s reasonable to either just decide to do it for 6 months or to do it until the CD4 count recovers. I think either of those are an option. And I always think too about just my patient, their other health conditions. Are they a 38-year-old marathon runner who has excellent immune function? Are they someone that’s older that has other impacts on their immune system? DR LOVE: All right. Let me flip out a few more from Dr Kumar. Is it reasonable to give rituximab as a single agent first when they present with sepsis and then add cladribine? He also wants to know what’s up with BRAF therapy? DR ROGERS: Yes. So this is actually an outstanding question and kind of the second thing that I wanted to talk about with hairy cell leukemia is that we all know how effective purine analogues are, cladribine in particular because the treatment course is either 5 or 7 days, is very immunosuppressive and myelosuppressive and should not be given to patients with active infection. Pentostatin, which is less myelosuppressive because it’s given every 2 weeks until response, has some data in infection. And in fact, our institution published the use of lower dose pentostatin to start, so kind of like a half dose until people recovered from infection. However, I do think that there are really good alternatives for infected patients that I would encourage over use of purine analogues, either cladribine or pentostatin. It is absolutely reasonable to do rituximab until people recover from sepsis, but if people have classic hairy cell leukemia and are confirmed to have the BRAF V600E mutation, I actually think use of vemurafenib is an even better idea. So for anyone that doesn’t follow hairy cell really closely, there was an NEJM article a few years ago looking at use of single agent vemurafenib in the relapsed refractory setting and the time to neutrophil count recovery is really short. I think it’s a median of around 4 weeks, but we’ve seen it as quickly as a week. So this is an excellent way to get rapid immune reconstitution in patients with hairy cell presenting with neutropenia and life threatening infections. So I myself have used this strategy to give the BRAF inhibitor, vemurafenib, in people presenting with new diagnosis hairy cell cytopenias and like blastopneumonia, other fungal infections. And then we actually, our institution, has published a case series of 3 patients where we had given them pentostatin and then they developed life threatening infections and we treated them with vemurafenib with good success. And I know others have done this too. So for people with fairy cell presenting with infection and need to improve cytopenias, I actually would suggest vemurafenib. The duration of — or I think it’s actually relapse free survival is what they calculated, but kind of the progression free survival is shorter, so it doesn’t work for like 10 years like cladribine, so you get like 2 years instead of 10. But if you’re going to die of sepsis, none of that is good. So I think it’s a great strategy to give vemurafenib, fix people’s neutrophil counts, get them better, then if they relapse at 2 years, which is sooner than the 10 maybe you’d expect with cladribine, you can go ahead and give them cladribine then when they’re not infected and at risk for like worsening infection, sepsis or death with the purine analogues. Not to complicate things further, but there is now a publication of the use of rituximab with concurrent vemurafenib. It’s a really complex dosing strategy. And that actually extends the relapse free survival with the use of vemurafenib even longer. Again, it hasn’t been compared to purine analogues, but I think that’s a great option too for patients where purine analogues are not advisable. DR LOVE: Susanna says this patient that she asked you about actually is BRAF mutated in this first line situation. Interesting thought there. I’m curious, you don’t hear too much about vemurafenib. And I’m not sure you have sunlight there in Columbus, but I used to hear terrible stories about sunburn. Have you seen any of that? DR ROGERS: I have not because I usually remind people pretty aggressively about the phototoxicity. So because the relapse free survival is shorter and it’s not been studied in a first line setting, I’ve only used it first line for patients with active infection or actually during the pandemic, there was someone that needed treatment that couldn’t avoid COVID exposure, this was earlier in the pandemic before vaccines and Evusheld and other protective measures. So it's really more of a relapsed refractory or infected patient kind of option. Also, the dose that was studied is the melanoma dosing which is 960 BID, but there’s a couple really nice papers by some Europeans showing that half that dose is likely adequate. So I’ve also tended to give the lower dose to people which is much more tolerable for extended use and that might improve the phototoxicity a little bit too. But no, I actually remind people at every appointment to wear sunscreen and never go outside. Plus, I live in Ohio. DR LOVE: K S Kumar wants to know what fraction of patients with hairy cell are BRAF mutated? Like almost all? What fraction? DR ROGERS: So classic hairy cell patients, it’s about 98% are BRAF mutated. Patients with a variant of hairy cell leukemia are not BRAF mutated. But it’s about 98% of classic hairy cell patients at diagnosis are BRAF mutated. DR LOVE: So I knew when I decided to start with the hairy cell thing that I wasn’t going to want to get off the topic, but we will get off it although probably we’ll get more questions. But I have to ask one more thing. Where are we today with moxetumomab which I can never pronounce? When is it used? Have you used it? What do you see when you use it? DR ROGERS: So moxetumomab pasudotox is an antibody drug conjugate that is actually FDA approved for the treatment of hairy cell leukemia after 2 prior treatments including purine analogues. I have definitely used it and it can work very well. So moxetumomab pasudotox kind of fills this space of what do you do for people where purine analogues aren’t getting the job done? So for people who are fit, healthy and can get purine analogues, had a good first remission duration with them, can get them again, really the efficacy is so outstanding, those should be used again either with or without rituximab. There are patients that have very short remission duration, so less than 2 years from purine analogues. And if you’ve done cladribine or pentostatin 3 times in 6 years, it’s really best to pick something else. So moxetumomab pasudotox falls into this group of drugs we now have in hairy cell leukemia that aren’t purine analogues that can be highly effective. So it’s moxetumomab pasudotox, vemurafenib is in this group, of course, not FDA approved for hairy cell leukemia, but very well studied. And then, we’ve led a Phase II study of ibrutinib in hairy cell leukemia in this population and people with a variant and it can be very effective. So hairy cell now has this grouping of drugs that can work very well for patients where purine analogues are unsuitable. And I think we’ve already covered kind of like infection where purine analogues are unsuitable. So these are drugs for where cladribine or pentostatin is not going to get the job done on a disease standpoint, like it’s just not effective enough. So I’ve used it. It’s kind of unique dosing. So it’s given like kind of Monday, Wednesday, Friday, every 4 weeks for up to 6 cycles. Based on the study, there’s not a super good way to talk to people about what the PFS is, but I’ve seen some very good results in the few people I’ve treated and I definitely support that as a very useful drug. It has some unique toxicity. So it can cause both capillary leak syndrome and it’s more of like an atypical hemolytic uremic syndrome like TMA type thing that’s usually self-limited. Both are actually self-limited if they occur for the most part, but you just have to be aware of those unique toxicities if you’re going to prescribe it. DR LOVE: So I don’t know why I just flashed on the first time I did an interview with Hagop Kantarjian and the first thing I said was what’s new in CLL? The next thing I knew, it was 15 minutes later and I was fascinated. So anyhow. Let’s keep it going. Case: A man in his late 50s with newly diagnosed chronic lymphocytic leukemia (CLL) with an IGHV mutation — Jeanne Palmer, MD DR LOVE: Well let’s drop into the more common issues that come up in oncology practice in terms of CLL. And we have 3 cases. As always, no 2 cases of CLL ever seem to be the same. Let’s start out with this patient of Dr Jeanne Palmer, a 57-year-old man, newly diagnosed CLL, IGVH mutant. Of course, that subset of a younger patient, IGVH mutant disease has been interesting to talk about. Here’s Dr Palmer. DR PALMER: 57-year-old gentleman who presents with a white blood cell count of 155,000. So this is just a peripheral blood film for CLL. The letter A points to a smudge cell. And the letter B points to a CLL cell. You’ll see kind of a large nucleus and very little cytoplasm. CT scan showed diffuse lymphadenopathy. There was splenomegaly noted at 20 cm. The patient was initiated on acalabrutinib 100 mg twice daily with obinutuzumab for 6 months. And at 6 months, the patient had complete normalization of blood counts as well as CR based on CT scans. One of the attractive aspects of venetoclax and obinutuzumab together is that it’s actually a limited 12 months of therapy. How do you choose the first line therapy? There’s so many different potential options and they all have sort of different benefits to them. What are things that would make you choose one over the other? DR LOVE: So it seems like a simple question and we certainly have asked it an awful lot in the last couple years and it seems like every time we ask it, it gets more complicated which is choice of first line therapy. Just to point out, this patient got acala and obinutuzumab. And then along the way, maybe the patient started thinking about, hey it’d be great to stop this at some point and so she brings up this question. But maybe you can just kind of comment in general about how you think through first line therapy. Any thoughts about this particular subset? And what about the patient who suddenly hears about limited therapy and wants to switch? DR ROGERS: Yeah. So we could probably spend like the rest of the time for this program talking about just this question because this is very difficult. So the way I think about these are 2 things. One is what are the CLL disease factors and what kind of therapy might be best for the CLL disease? And then also, what are the patient factors or preferences that might help us select one of these? So this patient who is under 65, fit has never had treatment, also has very good risk disease, so they are mutated which is great, and have trisomy 12, so they do not have del(17p). They didn’t say whether or not this person has a TP53 mutation because I don’t know if that was tested. But for the purposes of the discussion, we’ll just assume that they don’t have a TP53 mutation because that goes kind of in with 17p as something that’s high-risk and has to be handled differently. So a couple years ago, the discussion was this is the group of people we can cure with FCR meaning about half the people in this spot that take FCR have no detectable leukemia at 12 years. And so I think that’s worth discussing, but the affinity for anyone to take chemoimmunotherapy now is pretty close to zero, given the side effects. And I’ve had no one even consider that in a very long time. But this is someone that has potential for curative type therapy with FCR. This is also someone that’s going to do very well with whatever you choose to do. So for initial treatment, the IGHV mutated group are the ones that do the best compared to unmutated when you’re looking at the ven/obin fixed duration treatment for a year like CLL14. These patients also do outstanding with BTK inhibitors. So I don’t know that there’s a bad choice disease-wise. And I think as far as what you would offer for CLL efficacy, either the BTK inhibitor or the ven/obin would both be excellent options. I don’t think there’s a bad choice there. So now, we’ve got kind of like, hey this is a lateral for this person’s disease. Then, you kind of go like, what are their comorbidities? So if they have heart failure, renal failure, something that would make venetoclax challenging, then you’d really go with the BTK inhibitor. If they require warfarin for mechanical heart valve, have difficult to control AFib, something that would make the BTK inhibitor less attractive, then you would go the other way. So you kind of say, okay what are the key comorbidities that sway our decision one way or the other? So it’s kind of like, what’s best for their disease? What’s best for their key comorbidities? Because that really can flip what you think. And if all that’s a lateral like with this patient, then you just talk to them about what’s better for them as a person. And I’ve had a lot of people that are like, yeah I want this done in a year, I’m young, I’m healthy, I don’t want to take pills forever, give me the 1 year, that’s what I want. And then, I’ve oddly had some patients that are like, yeah I’m not coming for all those appointments to get obinutuzumab and then start this, I have a fulltime job, I’m not putting up with that, just give me those pills, I want to go back to what I was doing. So I think, you know, they’re like I don’t even care if I take pills every day for the rest of my life, which, again, is probably not really the rest of your life, right? So BTK inhibitors are given indefinitely, but we don’t really know how long people need them for. That’s an ongoing question. And also, if you’re 57, the rest of your life is 3 decades. I’m pretty sure we’ll come up with something in 3 decades that you don’t have to take it that long. But long-term pill therapy, sometimes people choose that because they don’t want the appointments associated with starting venetoclax and getting obin. So those are kind of the patient preference side. So this is really something where you have to sit down with the person and really understand what matters most to them when you’ve got either choice being great for the disease, either choice being great in terms of comorbidities in a fit, younger person. The addition of an anti-CD20 to a BTK inhibitor is a really interesting question. So we know that rituximab doesn’t help when you add it to ibrutinib. The PFS is the same with a hazard ratio of 1 in a randomized Phase III study. I do think that it is worth considering giving obinutuzumab with acalabrutinib because you do see an improvement in PFS in all categories except for those with deletion 17p. So if people are willing to come for the obin and do that, I think it would be a benefit and I would offer that to people. During the pandemic, I have tried not to use as much anti-CD20s and so kind of the way I’ve thought about it at the height of COVID was that the increased COVID risk is not worth the small benefit in PFS. But I do think with hopefully ongoing improvements in the pandemic and certainly, a more safe situation for our patients now than 2 years ago, there is a benefit to doing it with the obin. I don’t know if obinutuzumab adds a lot to ibrutinib or not and I don’t know of any randomized data to really help us there. DR LOVE: Of course, there’s been a lot of discussion over the last couple years about anti-CD20 and COVID and I think people are still concerned about it. Do we have any data comparing obinutuzumab and rituximab in terms of COVID or any theoretical considerations? DR ROGERS: No. None that I’m aware of. They’re both very B-cell depleting and it’s probably depletion of healthy B-cells. And from the noncancer population that patients with rheumatologic disease taking these antibodies also just have like no antibody — or taking these therapeutic anti-CD20 antibodies have like no therapeutic response to vaccines in terms of antibody production. Then when you look at CLL, you’re taking a group of people that have low antibody production in response to vaccines at baseline and then suppressing it further. So I actually don’t know any difference between the 2. That would be interesting to know. I expect in terms of COVID risk, it’s probably similar. Case: A woman in her mid 60s under observation for CLL for 6 years who now presents with worsening symptoms — Alexey V Danilov, MD, PhD DR LOVE: So a question from Baskara in the chat room, how would you manage lymphocytosis of greater than 400,000 with ibrutinib? But before you answer that, I’d like you to look at the next case because that sort of relates to that. So I know you work with Dr Danilov. And this is the first of 2 cases that I’m going to present from him. A 64-year-old woman who he had been observing for some time now presented with worsening symptoms. Here’s Dr Danilov. DR DANILOV: 64-year-old woman who was diagnosed with CLL 6 years ago. And she was followed by watch and wait. And now she presents with worsening fatigue, weight loss, progressive lymphadenopathy. So she starts ibrutinib about 1 month ago and now returns for a follow-up. So the white blood cell count went up from 24,000 to 120,000. So what would the audience do in this case? DR LOVE: The audience says keep going. DR DANILOV: Yes. All right. So she continues ibrutinib and then 1 month later, white blood cell count starts to come down. Now, it’s 100,000. However, the patient develops diffuse rash and bad arthralgias and you try Tylenol, you try some quinine, some magic, nothing seems to work. So what would be the next best step at this point? What would you guys do? DR LOVE: So what’s the follow-up on the patient? DR DANILOV: She actually went on acalabrutinib and is doing fine. DR LOVE: So any thoughts about this case? And also, managing patients whose white counts are going up on BTK? This patient, I think, he said went up to 120. What about when you start to get up to 400? You hear cases of people where it doesn’t come down for a long time. What do you say to the patient? Any other thoughts about this case? DR ROGERS: Yeah. So I definitely have some thoughts about this case because I think BTK inhibitor intolerance is super interesting. But I actually don’t consider lymphocytosis a barrier to using BTK inhibitors. We know from some older studies that were done before the advent of more effective therapies that people can get leukostasis with CLL, but it’s usually up around 600,000 and even in those cases, it’s not all patients. So I usually just press on, even at 400,000, and I don’t do anything to lower the lymphocyte count unless it becomes symptomatic in some way. So if you do have people that you think have symptoms of leukostasis, then I think it is reasonable to think, should we do something to reduce the lymphocyte count? But usually, I just, you know, okay it’s 400,000, that’s fine and use reassurance. It’s always a little unnerving to start a BTK inhibitor when someone’s lymphocyte count is 400,000 because it can go up higher. I actually did that and had someone go up to just over 700,000 and she was feeling completely fine, but I did tell her to stop taking the BTK inhibitor for a couple days. And if they stop that, the lymphocytosis that’s a redistribution lymphocytosis goes away in like 24 to 48 hours. So if you ever do get someone to a level of lymphocyte count that they are symptomatic at or that maybe you’re uncomfortable with, you can always tell them to stop the drug and it’ll decrease very quickly to close to what their baseline was before they started the BTK inhibitor. So I’m actually not worried about 400,000, but if they’re symptomatic or there’s other reasons you want to reduce it, I think adding an anti-CD20 is certainly reasonable, especially they’re approved in combination with BTK inhibitors and that will lower the lymphocyte count really quickly and make everybody happier. And if someone’s getting symptoms with leukostasis, certainly resolve that for them. I don’t usually add an anti-CD20 just for that reason, but I think that’s a really nice option. In terms of — I’m trying to remember what the other thing was I just wanted to say about this and I lost my idea. Oh. I usually — DR LOVE: Maybe it’ll — DR ROGERS: Yeah. It came to me. So I usually counsel people that their lymphocyte count will remain elevated for some time and we know that actually doesn’t decrease the PFS, it might actually improve the progression free survival. So I usually tell people that it’s a good thing, don’t worry about it, it’s that the lymphocytes will remain elevated in their blood for a long time. And I always counsel people before starting a BTK inhibitor to expect the white count to go really high with the hope that some will get disappointed if it only goes from like 100 to like 250 if it doesn’t go up really high. I try to build it up like it’s going to go really high so that the patient doesn’t get alarmed. But usually, it’s just a lot of counseling that this is normal. Unless their count goes down like they respond and then starts going up again like they’re developing resistance, I don’t worry about it. DR LOVE: So Lilly in the chat room wants to know whether lymphocyte doubling time should be a criteria for treatment initiation? She says that it’s not clear to her looking at NCCN, et cetera. Is it clear to you? DR ROGERS: Yeah. So it goes in and out of the guidelines, so I do think that the information out there on that is a little unclear because it was in the iwCLL and then I believe they took it out. However, if you ask most people that treat CLL for a large part of their practice like most of my practice is CLL, most of them do not use lymphocyte doubling time in that. Most actually just won’t consider that. You also have to have an absolute lymphocyte count over 30 to even consider doubling time. So going from like 10 to 20 is not really significant. So it has to be an ALC over 30 in doubling although most people that treat a lot of CLL don’t consider that. I will say though if the lymphocyte count gets really high really fast, that is really a reason. So I had someone go from 20 to 200 in 3 months. That would lead me to do something. So if it does increase very dramatically, the trajectory is not good, but also at that time, people usually have other symptoms. Like that person’s platelet count had fallen, they were having lymphadenopathy and had lost weight. So if you see a dramatic increase in white count, usually you see other things that make you think, hey it’s time to do something about this. But I don’t use doubling time myself. Most people don’t. I do think a rapid increase in lymphocyte count matters. And I will say it is completely confusing because different guidelines either have this or don’t. So there is no clear guideline out there on this one. DR LOVE: So this patient that he just presented had problems with rash and arthralgias. And you’ve done a lot of work and published on noninfectious, noncardiac complications of BTK. He was talking about quinine, magic, et cetera. Any pearls on how to deal with dermatologic issues and arthralgias? DR ROGERS: Yeah. I think if I had a trick for this, I’d be really rich and famous because it’s really impactful for people’s lives, right? And that’s one of those things where unless the rash is like all over or you have that inflammatory arthritis that people get early, the physician is kind of like, yeah, okay, you have a rash or sure, your joints are whatever, like this isn’t limiting. But for people who are experiencing this every day, this can be really important for their everyday life. I’ve had a couple of people with rashes that didn’t look so bad, but was a cosmetic problem for them or arthralgias that they’re just like, gosh, this is a drag, I’ve been taking this 2 and a half years, this is really unpleasant, I’ve tried electrolytes, I’ve tried tonic water, I’ve tried therapeutic massage, I’ve tried, you know. And so even though we might not think of that as a high-grade or substantial toxicity, when you consider these long duration treatments, it can be very important. I think what Dr Danilov was saying is a really good strategy and it’s one that’s been studied prospectively and that’s switching to a different BTK inhibitor. So there are some toxicities that are for the same class, but some of them are actually off-target toxicities. So ibrutinib, the first in class drug, tends to have the most side effects. So switching to either acalabrutinib or off-label zanubrutinib is an option. So zanubrutinib is not currently approved for CLL unless that happened really recently and I missed it, but it’s been studied really well and we expect it will be. And it is in the NCCN guidelines for BTK inhibitor intolerant patients. So I think switching up which BTK inhibitor you’re using can be really helpful. And we have a Phase II study with acalabrutinib showing that patients who discontinued ibrutinib for adverse events, and there was criteria for what they had to be, who started acalabrutinib then, so restarted BTK inhibitor with acalabrutinib, most of them were able to tolerate acalabrutinib and respond to that. And there’s similar data actually with zanubrutinib. So I do think this is a great strategy. I haven’t seen too many patients go the other way and stop acalabrutinib for intolerance and go to ibrutinib although I’d certainly try it if they couldn’t tolerate the other 2. Whenever I talk about this too, it’s really important to note that zanubrutinib, acalabrutinib and ibrutinib have the same mechanism, so they bind BTK at the same site. So do not switch between these drugs for disease progression or resistance to therapy. That’s not going to work. But for intolerance, this is an outstanding strategy. DR LOVE: And here’s a paper. I didn’t know what Haematologica is. Is that, I guess that’s in English, but I haven’t heard of that one. In any event, this is the paper talking about your experience. Case: A man in his mid 70s with multiple regimen-relapsed CLL, complex karyotype — Dr Danilov DR LOVE: I want to get back to another case that we have for Dr Danilov who asked the question of what you would do with this patient. And a lot of times when I hear these cases presented, I’m sure everybody thinks about this every now and then, I go what would I do if it were me? Audience, that’s what I want to ask you and that’s what I want to ask you also, Kerry. Here's this 76-year-old man. DR DANILOV: He was diagnosed with CLL 15 years ago. He was treated with bendamustine and rituximab for 6 cycles. And then, he was treated with ibrutinib, progressed and currently, he is on venetoclax. So now, he again presents with progressive disease, fatigue, progressive lymphadenopathy, white blood cell count of 6,000, hemoglobin is 10.8, so mild anemia. And CT chest, abdomen and pelvis shows diffuse lymphadenopathy, abdominal mass of 16 cm. So what would be the next best step here? In this particular patient, PET CT demonstrates SUV of 5 in the abdominal mass. We do a biopsy anyway and the biopsy confirms CLL. There is no evidence of transformation. FISH reveals complex karyotype. So what is the next best step for this patient? DR LOVE: So what’s your answer? DR ROGERS: Yeah. So most of the times these days in CLL, I spend all this time in my clinic convincing people that they’re not dying, right? So, hey you should get back to your life, you’re on observation, hey oh you need treatment, don’t panic, we have these magic pills. In fact, we have 2 kinds of magic pills. Then those magic pills don’t work, we’ve got the second one because we’ve got both BTK inhibitors and BCL2 inhibitors. This is someone where we’ve run out of magic pills for them and we don’t have a quick, easy standard therapy that’s going to make this better for this person. And this is the group of people that are really still at risk for mortality from CLL itself. I just want to highlight that Dr Danilov said something very important and that’s he did a PET scan and then a biopsy. So in people who progress on these targeted agents, ibrutinib and venetoclax, the SUV usually is to determine whether or not people might have Richter’s. So kind of like 6 and up, you worry they have Richter’s. But actually, in people progressing on BTK inhibitors or venetoclax, the SUV is less predictive of whether or not it’s Richter’s. So it’s good he did that biopsy. But what you’re stuck with here is what we kind of started calling double refractory CLL or CLL that’s refractory to our 2 kind of best classes of agents, so BTK inhibitors and venetoclax. This is the group of person that needs to be referred for a clinical trial to get something novel and ultimately, likely cellular therapy. So there are some drugs that have efficacy and have made an impact in this space. These are drugs that are not yet approved. So the only kind of approved class of drug that this person hasn’t gotten would be PI3 kinase inhibitors. There’s not a lot of data in resistant disease with those and we don’t expect them to work well based on the mechanism. So there are some novel agents that can work well. One is drugs like pirtobrutinib and those are reversible BTK inhibitors that bind at a site other than where the currently approved BTK inhibitors, ibrutinib and acalabrutinib, bind. So those can be effective in double refractory disease and there’s some clinical trial data showing that. The progression free survival is still kind of unknown. But that can be highly effective. There’s also drugs in development like PKC-beta inhibitors. I think maybe cyclin-dependent kinase inhibitors will be useful here. So it really is a situation where you need to find a new class of drug. I do think cellular therapies are very suitable for these patients, particularly things like CAR T-cell therapy. I’m not sure with that lymph node mass, what kind of state you’d need someone in to proceed with that. And, of course, they have to be fit for it and it’s still investigational in CLL, so it would mean participation in a clinical trial. But this is someone who needs to be on a research study and needs to be referred to a center that can do cellular therapies. There are some novel CAR T constructs, I think, coming along that will be nice. We keep getting a little bit better at CAR T in CLL and this is the person that needs that. The last thing I’ll say is if you have someone that you cannot get to some place for a clinical trial, there is some efficacy of starting combination BTK inhibitor/venetoclax in this population. There’s not prospective data here in this population, not even really solid retrospective data. But anecdotally, that combination can work in those who are resistant to both agents as a single agent. So if you really can’t get someone to a novel therapy, that would be an option. DR LOVE: So you were talking about approved options, but there are a lot of times when you start seeing drugs that aren’t approved that look so effective that when I sit down and say, well what would you like to be treated with? Because when I heard that case, the first thing I thought about was I want pirtobrutinib. Do you think we have enough data right now that that would be your preferred, if it were available, you would just do it? DR ROGERS: If I couldn’t put them in a research study, yes. So I work somewhere where we actually have very good investigational options for this population and pirtobrutinib was one of those options although the study we have with it is now closed. But, yes. I think if I could just give this person pirtobrutinib and they were not able to go on a clinical trial, that is what I would do. That is the drug currently with the best efficacy I’ve seen in this space and it’s very tolerable. And I have patients receiving pirtobrutinib on study after just this situation that are doing very well. I do think too a major issue here just in treating these patients is a change in mindset. Because their whole experience has been like don’t worry about it, you don’t need to do anything, then okay take this BTK inhibitor, things are good, okay take venetoclax, things are good. And some of them are like hold up, I need to go somewhere and be in a research study? Or like I have to come for a trial with monthly visits? So preparing patients who are on a second line targeted agent that the next one might not be as fun and easy as the last 2, I think is really important as well. DR LOVE: So I promised the audience last night on our lung cancer webinar when I said we were doing this today that I was going to ask you to explain the difference between covalent and noncovalent BTK and does that have something to do with why you see responses to pirtobrutinib after the other BTKs? Want to tackle that one? DR ROGERS: Yeah. I can. So covalent or noncovalent is actually just the type of binding the drug has to the protein. In limiting this to BTK inhibitors, the covalent ones irreversibly bind at the same site. So ibrutinib, acalabrutinib and zanubrutinib are all the covalent ones and they all irreversibly bind at the same site. The noncovalent ones bind reversibly, meaning they bind and unbind the protein continually. So that limits toxicity a little bit because it doesn’t permanently inhibit anything. But I think while we’re talking about resistance, so there’s a bunch of theoretical stuff about why resistance, is one better than the other overall for resistance? But I think the major reason that the noncovalent ones work after the covalent ones is that they bind at a different site. So the covalent ones bind at the C481 residue, the noncovalent ones bind at different sites on BTK. So that’s why they work after, I’m just going to say ibrutinib referring to those 3 for simplicity’s sake. So that’s why like pirtobrutinib would work after ibrutinib. It’s not that it’s covalent or noncovalent. So the actual type of binding isn’t what makes the difference there, it’s the place they bind. It’s just the way they were developed, the noncovalent ones bind in different areas. The other thing that I just want to mention briefly is that there was an article that came out looking at resistance to pirtobrutinib. And resistance to pirtobrutinib actually would predict that drugs like ibrutinib wouldn’t work after it. So that kind of matters when we’re looking at how we want to develop sequencing of these drugs in the future. So if you give someone pirtobrutinib as a first treatment and they become resistant to it, theoretically, it’s pretty unlikely that they’ll be able to take ibrutinib later. But the opposite, if you take ibrutinib until you’re resistant, a good number of those people will respond to pirtobrutinib. So there are some mutations that confer resistance to ibrutinib, you develop on ibrutinib that mean pirto won’t work, but I think if you develop resistance to pirto, it’s much less likely ibrutinib will work. DR LOVE: So I want to move on and ask you about another of your interests which is immune cytopenias, particularly with CLL. Before we get into a couple of cases, we actually have a question in the chat room about people with autoimmune cytopenias who don’t respond to IVIg and high-dose prednisone despite good control of the CLL. What do you do in that situation? Multi-day course of IVIg? Four days of high-dose dex? If you do the latter, do you taper after the 4 days? Any thoughts about this scenario? And how often do you see it? DR ROGERS: Yeah. So very common. So just talking about ITP and AIHA and not really talking about pure red cell aplasia, it occurs in somewhere between 5 and 25% of people with CLL. The lowest reported incidence is just under 5%. The highest report is just over 25%. And it depends on who your cohort is. So like untreated, closer to diagnosis is less common than people extensively treated with higher risk features. So this is actually very common in our CLL population and is treated as an independent disorder. So you don’t have to treat the CLL just because you have ITP or AIHA. AIHA is more common than ITP in CLL patients, or more frequent I should say. But if it does not respond to standard therapies for AIHA or ITP, then you do think about treating the CLL. And this has actually gotten kind of interesting. So steroids are still the first line because in a lot of cases, you can like resolve it, meaning it will never happen again and their hemolysis or thrombocytopenia goes away. IVIg is great because it works fast. So you’ll see like a rapid improvement in counts. But I actually do not ever expect long-term improvement with IVIg because it mostly just blocks clearance of antibody coded cells. So you see it wear off after about 4 weeks. So unless you fix the immune response, you just have to keep redosing IVIg at high doses. So it’s about 1 gram per kilo 2 days in a row or same, but spread out over 5 days. So it’s a lot of IVIg compared to the replacement for hypogammaglobulinemia. I do actually use a lot of anti-CD20 monoclonal antibodies in CLL patients with autoimmune cytopenia. And there’s actually a study reported even with like obin can be effective there, rituximab is very commonly used there. Then there’s, of course, the other drugs just for like primary ITP that you can use like eltrombopag or romiplostim are both effective in CLL associated ITP if you don’t actually need CLL therapy. So you obviously have to have good bone marrow function. You wouldn’t do that for someone with heavy bone marrow infiltration that has cytopenia for that reason as well. So those are useful. But I think the most interesting thing is actually so this patient that the person was asking about doesn’t need CLL treatment. It sounds like their CLL is well controlled. So I would really crack into that primary ITP toolbox with the thrombopoietin receptor agonist, maybe an anti-CD20. You can even use things like mycophenolate or cyclosporine in these cases for immunosuppression. But if people have a reasonable CLL disease burden, B-cell receptor signaling antagonists can work in autoimmune cytopenias. So both BTK inhibitors and actually there is cohort study data with idelalisib that that’s helpful. And that’s probably because inhibiting B-cell receptor signaling and the kind of bystander normal B-cells that generate these antibody responses in CLL associated ITP and AIHA, that is actually minimized by blocking B-cell receptor signaling. So my guess would be that’s why it works. But we did a study here, and many other people have too, showing a very low incidence of AIHA and ITP during BTK inhibitor treatment. And, I think it was Vitale, published a very nice cohort study showing that the incidence with venetoclax is much higher. So BTK inhibitors likely have a beneficial effect. And actually, Dr Danilov and I are conducting a study looking at acalabrutinib prospectively and specifically for CLL associated AIHA. So he’s the lead investigator on that. So I do think that we will hope to have prospective interventional data on BTK inhibitors. And that’s for patients who didn’t respond to first line steroids. DR LOVE: So I want to have you look at a couple of cases from practice. But before we do, any myths or misperceptions out there in the community oncology setting about autoimmune cytopenias, things you see people doing that you wouldn’t do? DR ROGERS: That’s a great question. I think a couple things I see that get done a lot which I can understand, but one is people tend to shorten the duration of steroids. So dex for 4 days is a regimen, but if you do prednisone 1 mg per kilo, you really have to, I try to get it down to like 40 mg or less quickly if they respond, but you really have to taper it over 4 to 6 months. So I see a lot of people that taper it over 4 to 6 weeks and then the autoimmune cytopenia comes back. I also think, it’s not like a myth or misperception, but for people that don’t need CLL treatment, we used to just do like the whole gamut of primary AIHA or ITP therapies to avoid doing chemotherapy for CLL, but I very much think in this new era of targeted agents, people should be faster to just go ahead and give actually BTK inhibitors probably based on mechanism, but venetoclax too if appropriate. People should be faster to use those things sooner than you’ve given people 6 months of immunosuppressants. DR LOVE: So before we go on to the next case, one other question I’ve been meaning to ask you. We saw at ASH one of the cases the patient preferred ibrutinib because it was once a day. There was some data presented at ASH on once a day acala preparation. Do you think that’s going to end up in practice in the near future? Do you know anything about that? DR ROGERS: I haven’t heard it was once a day. I did hear there was one that doesn’t require — DR LOVE: Well, yeah. No, I’m sorry. I meant to say that you could take a PPI with it. DR ROGERS: Oh. Okay. Yeah. Because zanubrutinib has a once a day too. DR LOVE: Right. Yeah. Yeah. DR ROGERS: So I think that’s going to matter. Yeah. DR LOVE: It was the PPIs. DR ROGERS: The PPI one. Yeah. So I do think this will make a difference because I live in Ohio and the incidence of GERD here is very high and I’ve had some patients that really needed acalabrutinib and were just miserable, especially I had someone with ibrutinib intolerance, very early into treatment, had to switch them to acalabrutinib, they had to switch to an H2 blocker, you have to take it 2 hours after you take the acalabrutinib. And they’re like, but that’s in the middle of my golf. I’m like I know, I’m so sorry. Like you have to bring it with you to the golf course. It’s inconvenient to take it 2 hours delayed. And then they’re like it’s not working and my heartburn is back. And I’m like I know, I’m really sorry. So I actually do think that’s good. And I’ve had a couple people taking acalabrutinib that couldn’t live without PPIs that were taking them together and I always just like worry that this might negatively impact their outcome with acalabrutinib. And then, just going back to the dosing scheme, oddly, there are some people, you know, taking drugs more than twice a day is hardly, but oddly, I have some people where it’s like once a day. So I do think that’s an advantage too to ibrutinib or zanubrutinib as a daily. Case: A man in his late 70s with newly diagnosed CLL and significant neutropenia — Amany R Keruakous, MD, MS DR LOVE: All right. Well let’s go through a couple of cases. First, by Dr Keruakous, a 78-year-old man with newly diagnosed CLL and neutropenia. DR KERUAKOUS: 78-year-old man. He had a history of monoclonal B cell lymphocytosis for 8 years. Didn’t have any B symptoms or cytopenias to require treatment. He was referred to me in clinic to evaluate new onset neutropenia. He did not have any recent infections or hospitalizations. He didn’t have any B symptoms. No lymph nodes or hepatosplenomegaly on physical exam. And on history, he did not have any new medications started that would explain this neutropenia. His lab work showed WBCs of 1.3 with absolute neutrophil count of 100. Otherwise, normal. Nutritional workup was all unremarkable. And virology also negative. So we did a peripheral flow on him. He had an aberrant mature B cell population that was positive for CD5 and CD23 markers for CLL. He had a negative cyclin D1. Bone marrow eval for this patient proved involvement of B cell lymphoproliferative process. He had negative p53, cyclin D1 and he had an IGH loss. He had a good performance status and otherwise, no other medical history. What would you do for a patient with only 1 single line cytopenia, only neutropenia? DR LOVE: So any thoughts about this case? What’s going on? What would you do? DR ROGERS: Yeah. This is an excellent case with multiple points for discussion. One is I might have like missed it. I thought she said the total white blood cell count was 1.3 like 1,300. And if that’s true, then they would not meet criteria for CLL. We have to have a clonal lymphocyte count of 5,000. So it’d probably be more like SLL which is completely fine. But that was kind of an interesting feature of this. And then also, the marrow, I would love to know what percent involvement there was with the CLL clone because in the most recent, this is not a really important point, but in the most recent revision to the iwCLL criteria in 2018, bone marrow infiltration causing cytopenias actually also qualifies as CLL. So isolated neutropenia due to bone marrow infiltration in CLL is extremely rare. So it’s not commonly encountered at all in practice. In fact, and I see a lot of CLL, I’ve only seen this once in a previously untreated patient where they had neutropenia due to bone marrow infiltration. Autoimmune neutropenia certainly occurs and I’ve probably seen more of that than the bone marrow infiltration neutropenia in CLL. And then, of course, we know drugs like venetoclax and ibrutinib cause neutropenia and the risk for neutropenic infections is actually lower with these than with chemotherapies. So I think there’s multiple causes for neutropenia in CLL patients that are interesting to consider. I do think that even if you’ve only got 1 cell line affected, if it’s due to bone marrow infiltration, that is absolutely a reason to treat CLL. And while neutropenia that’s isolated with a normal hemoglobin and platelet count is really uncommon. If this is bone marrow infiltration, I absolutely would treat the CLL. And actually, if it’s autoimmune, you could try standard immunosuppressive type therapies for autoimmune neutropenia. But I think you could also consider treating the CLL on that basis. So I would love to look at the bone marrow and see kind of which of those it was pointing to. That’s a super interesting case. DR LOVE: So actually, this patient was treated with ibrutinib. This was the patient who preferred it because he only wanted to take a pill once a day. I wonder if he’s happy about that. But in any event, just got started, responding, neutrophil count is now up to 1,200. So that was the route this patient took. Case: A woman in her mid 60s with relapsed CLL who experiences severe headaches on acalabrutinib — Bhavana (Tina) Bhatnagar, DO DR LOVE: I’d like to hear about one more case. This is actually your former colleague at Ohio State that went out into practice there, Dr Tina Bhatnagar, who has a 64-year-old lady who was diagnosed in 2007 at the age of 49. Observed until 2011, got FCR at that point, good disease control. 2021, she goes back, white count goes up to 123,000, anemia of 9, platelets normal, haptoglobin less than 8, thought to have autoimmune hematolytic anemia, treated with prednisone, still had anemia persistent. Follow-up bone marrow, hypercellular marrow, CLL 90% of cells, FISH del(17p). This patient was started on acalabrutinib, but as you’re going to hear, had problems with the acalabrutinib. Here’s Dr Bhatnagar. DR BHATNAGAR: She developed symptomatic lymphadenopathy and was treated with FCR chemotherapy and achieved good disease control. She was monitored until January of 2021, when her white blood cell counts that had previously been normal had jumped to 123k, and she started developing worsening anemia as well. Her serum haptoglobin was less than 8. She was believed to have an autoimmune hemolytic anemia and was treated with prednisone. She had some improvement of her anemia but not full improvement. She was started on acalabrutinib, and she was only on it for about a week before she started developing really severe headaches that were affecting her quality of life. And my first question is whether or not someone could comment on the frequency of BTK inhibitor-associated headaches and how do they typically manage them? And how long does that toxicity tend to last before it dissipates? Nowadays, is acalabrutinib the first line? Is it zanubrutinib? DR LOVE: I was reminded, I always love showing cases from her because, I saw you were looking down, her kids were like running past the window behind her. I always love talking to people in their home. I don’t know if you knew her kids when she was at Ohio State. DR ROGERS: Yeah. I’ve met both her kids. They’re adorable. And you’re lucky you’re not at my home because I have guinea pigs and they are very loud. DR LOVE: Wow. Guinea pigs. Wow. That’s different. Okay. Anyhow. What about this case? DR ROGERS: Okay so this has multiple interesting points. I think she made the point we were discussing earlier about autoimmune hemolytic anemia very well as this person had kind of nonresolution of AIHA and then got acalabrutinib and my guess would be that’s going to work really well for both the CLL that needed control with the heavy marrow infiltration and the residual autoimmune hemolytic anemia. So it kind of goes to the earlier point. I think the bigger issue here is the headaches for this individual. So headaches actually do seem to be fairly specific to acalabrutinib and really aren’t as frequent with the other BTK inhibitors, so it might be something that’s more of an acalabrutinib side effect than the other ones. They do tend to get better the longer you’ve been on it. So mostly by 4 to 6 months, they go away. And the vast majority of people will describe them as like a sudden onset headache that’s not that severe and then you ask them if they took something for it and they’re like, oh well, I was watching TV and by the next commercial it was gone anyway so I didn’t bother taking anything. So they’re like transient, not severe. However, there are people that really do get severe problematic headaches. And so caffeine containing preparations can really help, so like some of the non-aspirin containing Excedrin products can help. So like analgesics like that can help. And I think those are — staying hydrated and drinking caffeine can be beneficial, especially if you coach people to do that and then it gets better at a couple months with this. I know you’re going to be on the pill long-term, the headaches aren’t really forever. But you do really have some people that need to switch due to the headaches and I think this is a perfect opportunity to switch to a different BTK inhibitor. So she had mentioned there’s ibrutinib, acalabrutinib and then zanubrutinib and until zanubrutinib is FDA approved for CLL first line, I probably wouldn’t consider that as an option over the 2 approved ones. But if you’re switching for toxicity, I do think either ibrutinib or zanubrutinib would be an excellent choice for someone who needs to discontinue acalabrutinib for headaches. DR LOVE: So my apologies to the person in the chat room that wanted to ask you about transformation which we wanted to cover, but we’re not going to get to it today. But I do want to ask you one thing just in the interest of fair balance to our audience who sometimes watches all our stuff and that’s this question that we asked in the programs with Dr Wierda and Dr Hillmen, but I want to give you a chance. When you ask a question and you see 3 different answers among 6 people, you always know you’re in the right place. But audience, you tell me. What are you thinking about with a younger patient, we said age 60, unmutated IGHV, no del(17p) or TP53, what are you thinking about? And the thing, of course, that was stunning here is that 3 of these faculty people said venetoclax/ibrutinib. Others say venetoclax/obinutuzumab. You say either one. So would you like to kind of comment on this scenario? DR ROGERS: Yeah. So there were some Phase III studies that are now reported including the GLOW study in older patients comparing venetoclax/ibrutinib to obinutuzumab/chlorambucil that the approval of venetoclax and ibrutinib for a fixed duration is expected shortly. So this will become something we can offer our patients. I think a lot of work has to be done still to kind of see which patients might best benefit from that. So if you look at just the overall response rate and MRD kind of undetectable rates, it doesn’t look like it’s markedly better than venetoclax and obinutuzumab for a lot of patients. So I think we’re just going to have to think about in follow-up, which subgroups would benefit from this fixed duration BTK inhibitor/venetoclax combination where that might be better for them than venetoclax/obinutuzumab would be. So would patients with del(17p) do better with like a ven/ibrutinib fixed duration compared to like a ven/obin fixed duration? So I think understanding which disease types of CLL would most benefit from that combination is going to be really important in the coming years of follow-up. And then also, you’ve got to think about your patient comorbidities too. And remember that combination is kind of the worst of both worlds because you have both the venetoclax start up and side effects and the BTK inhibitor bleeding and cardiovascular side effects which granted are less because it’s only for a year, but those still matter. So it is all oral so you might have some patients that will not come for infusions, but you still have to come for ven escalation. So I think on the patient preference side and comorbidity side, it can be kind of worst of both worlds. So it’ll be really neat to see how that plays out. I think that is a very valid option to add to the other ones and with that approval coming, I look forward to seeing both the follow-up and how that plays out in practice. DR LOVE: So in terms of, one final question in terms of patient preference. It seems like when you present a case scenario of a younger patient, people think more about time-limited therapy. But I’m curious, do you think that younger people are more interested in time-limited therapy than older or do you think everybody is? DR ROGERS: I think everybody is. I know a lot of older patients actually are more concerned about drug cost because Medicare Part D has some of the greatest patient cost sharing responsibility compared to younger people with commercial insurance and I find that’s a big driver for time-limited therapy in older patients. I also have some younger patients that right now the biggest barrier to time-limited therapy is it requires venetoclax which has this escalation and I’ve got some younger patients that find out that they have to take that many days off work to come for the ven ramp up and won’t do it. So I’ve got some younger patients that just want to take pills and go back to their busy jobs, lives, managing their household. So I think that cuts both ways. And I do think that all ages are interested in fixed duration treatment. DR LOVE: So thank you so much for working with us today, Kerry. It was such a pleasure to work with you and hear how you take care of patients and all the excitement going on in clinical research in this disease. Audience, thank you for attending. Have a great weekend. Come on back on Tuesday. We’ll see what Dr Komrokji has to say about HMA/venetoclax in high-risk MDS and a whole bunch of other stuff. Be safe, stay well and have a great weekend. Thanks, Kerry. DR ROGERS: Thank you. It’s always fun. |