Tagraxofusp in BPDCN: Optimizing the Management of Adverse Events


Comprehensive discussion on the management of adverse events associated with tagraxofusp and how BPDCN care can be optimized in the setting of academic centers.


Thomas Leblanc, MD: Why don’t we talk a bit more about the patient experience of tagraxofusp and some of the important safety data that have come from this trial and the experiences overall with using this therapy. Tell me, Dr Patel, about your interpretation of these aspects and the results from this paper.

Bhumika Patel, MD: It was interesting. One of the things you’ve highlighted already is that about 20% of patients had capillary leak syndrome. About 7% of patients discontinued. So it shows that only a small percentage discontinued, but most of the AEs [adverse effects] were manageable. The cytopenias and capillary leak syndrome were manageable. I think as you’ve mentioned, in cycle 1 you would admit these patients to the hospital. So you are closely monitoring them for cytopenias and supporting them with transfusions and monitoring for capillary leak syndrome, so you can make sure they’re monitored closely in the intensive unit if needed, making sure they’re breathing OK and being diuresed appropriately. And if they need additional support with albumin infusions and stuff, they can receive them. Overall, from what I saw, the mortality rate was on the lower side because of close management. These patients could be treated appropriately in a clinical setting.

Thomas Leblanc, MD: This is really interesting to see. You’re absolutely right that there are very few instances of having to permanently discontinue tagraxofusp because of an adverse event. Yet there’s a pretty decent rate of capillary leak syndrome like you said, about 20% or so. So the tolerability profile does look pretty good overall compared to cytotoxic therapies. It’s just an unusual treatment around how much monitoring is needed up front and what kind of monitoring. I would point our listeners to the National Comprehensive Cancer Network[NCCN] guidelines about this. There’s a great page called Principles of Supportive Care for BPDCN [blastic plasmacytoid dendritic cell neoplasm], and it’s all about tagraxofusp, what you do about toxicity management and when to hold doses. It’s very clear and says patients have to have a baseline serum albumin of 3.2 [g/dL] or higher to be eligible to even start this therapy, and that if their albumin is under 3.5 [g/dL, it’s recommended to replete that, or to do so if there’s a reduction in at least 0.5 or more g/dL from their baseline value. I find it’s relatively common to have to give these patients albumin.

The other thing is you need to watch closely for changes in their body weight when they’re getting the treatment. It’s a daily therapy, days 1 through 5 of a 21-day cycle, but you can give those 5 doses ultimately over a 10-day period if you have to do dose delays or interruptions. That means you’ve got to be weighing those patients, which doesn’t always happen in the hospital depending on what type of unit the patient’s on and what the practice is there locally. We’re really good about doing this on a cardiology unit, but not as much so maybe on an oncology unit. So you’ve got to look at those weights, make sure they’re reliable, trend them, look at the blood pressure, temperature and heart rate, transaminases, creatinine clearance, and consider before every single dose whether that patient should get it.

What we tend to do is have the dose scheduled to be given so that it’s after the patient has been seen on rounds. It’ll be maybe early afternoon, so that we would see the patient in the morning. We’ll have their laboratory test results; we’ll have their weight. We’ll talk to them, assess how they’ve been doing. And only then does the pharmacy release and prepare the dose if we’ve said yes, the albumin looks good, they’re not having toxicities, go ahead and give that next dose. Because sometimes you do end up having to hold doses during that, especially the initial hospital stay, when you give those 5 doses. You also need to monitor these patients for a good 24 hours after that last dose before you rush them out of the hospital because sometimes things happen after they’ve gotten the last dose of this treatment. It’s very unusual and requires more care and concern and careful monitoring because it is an odd type of toxicity. But generally, you can get patients through it quite well, and most of the time you can give the second or third or later cycles in the outpatient setting without too much trouble. You don’t just want to order this, put it on autopilot, and then not see the patient. That’s when somebody could really get into trouble.

Bhumika Patel, MD: That brings up a good point, you definitely want to work with, the NCCN said you want to work with an academic center that has a lot of experience to make sure these patients are in good care when administering tagraxofusp because cycle 1 is a big determinant on dose interruptions, discontinuations, monitoring for capillary leak, and so that’s where it stresses the importance. Once the diagnosis is made or if there’s a question in the diagnosis, you want to make sure you’re working closely with an academic center that has been treating these patients more than in the community setting. Would you agree with that, Dr Leblanc?

Thomas Leblanc, MD: Yes, absolutely. I think that’s a really important and great idea. This is a very rare disease, so even for somebody like me who’s only seeing and treating patients with acute leukemias and myeloid diseases, and BPDCN fits in there because it’s such a close relative of AML [acute myeloid leukemia]. I see very few of these people on an annual basis even. So we have some experience giving this therapy. But if you’re in a community setting and seeing patients with all different kinds of diseases, even something like AML may be quite a bit less common and less familiar. This is far more rare than AML. We don’t even really know the true incidence of BPDCN, but it may be just 1000 or 2000 patients per year in the United States, or maybe even in the world. Whereas AML for example, there are probably about 21,000 or so cases per year in the United States, and even that is a relatively rare disease in a community practice.

I’m always happy to partner with my colleagues in the community to help figure out how to best care for these people in whatever way works well for these patients and families, with where they live, with what they want to do and go through, with whether they’re a transplant candidate or not, with whether that local treating clinician and center can give this therapy, if they’re comfortable with it. It’s important to have those partnerships with an academic center and community doctors to optimize the quality of care we provide to these patients.

Bhumika Patel, MD: To add to that, from clinical practice, biopsies are critical, skin biopsies and making sure you get a good specimen. This is a dermal invasion with BPDCN, which is one of the primary manifestations, along with other marrow and lymph node involvement. But I think getting a good biopsy is critical because I do know that due to the rarity of it, if you’re in the community setting, they may not be able to identify BPDCN if they’re not used to seeing it, and making sure they’re testing the markers CD123, CD4, and CD56. These are critical markers that we want to be sure about. There are a lot of times I send a request out to other institutions like Duke [Cancer Institute] for a second referral when I’m concerned that due to the rarity, are you sure this is the diagnosis? Whether it’s a cutaneous lymphoma of any sort. I think it’s great to partner up, and I think that’s stressed very eloquently in the NCCN guidelines, this multidisciplinary approach. Don’t take it on yourself, make sure to work with other experts in the field.

Thomas Leblanc, MD: That is a fantastic and important point, Dr Patel. If you have clinical suspicion for this disease, it’s really important and helpful to tell your pathologist about that because they may not have seen a case of this with how rare it is. They may not necessarily be running some of those markers. It may not be on their radar if this is a routine skin biopsy for a rash. It is very frequent that we see this disease get misdiagnosed or where there is a significant delay in the diagnosis because it’s so uncommon and unusual that if you don’t think about it, you can very easily miss it. So to highlight what you mentioned, CD123 staining and looking for CD123 by other methods such as flow cytometry if you’re able to send a flow sample, that’s really important.

What [Naveen] Pemmaraju, [MD,] has taught about this, the lead author of the article we’re talking about today, is to remember 1-2-3-4-5-6. So it’s CD123, CD4, and CD56. That is the typical phenotype of these cells, and it’s an unusual, rather unique phenotype. And it allows us to have this CD123-targeted therapy because every patient with BPDCN expresses that CD123 basically by definition. But just make sure that you tell your pathologists that you are thinking about or are worried about this possibility. I love the idea of sending it out for another set of eyes. With something this rare, that does sometimes change the diagnosis. And it’s a great practice for something challenging like this.

Transcript edited for clarity.

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