Advances in the Diagnosis and Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) - Episode 4

A Role for Tagraxofusp in First-Line Setting in BPDCN

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Expert perspectives on the first-line use of tagraxofusp, a CD123-directed therapy, in patients with blastic plasmacytoid dendritic cell neoplasm.


Naveen Pemmaraju, MD: This brings us to treatment. I’ll just remind you; we have a 71-year-old patient, fairly healthy, fairly extensive presentation of BPDCN [blastic plasmacytoid dendritic cell neoplasm] up front. What are your thoughts on treatment? We can divide it up into standard of care, whatever that means in BPDCN, and clinical trials. James, what are your thoughts, and then I’ll reveal to you how the patient was treated.

James McCloskey, MD: Looking over this patient, I think we’d do a PET [positron emission tomography] scan and a LP [lumbar puncture]. I know we’re going to talk about that, but a lumbar puncture is crucial at baseline to get a sense that he doesn’t have CNS [central nervous system] involvement. We have an older patient here, really fit, and he seems to be otherwise healthy, so at our center this would be a patient we’d be looking at to treat with targeted therapy probably. He fits really well into the data that we have available for Elzonris, or tagraxofusp, so that would probably be our go-to for this patient with intact organ function, with robust looking albumin at the start of treatment. At this time while we’re starting treatment, we’d also be looking at his options for an allogeneic stem cell transplant.

Naveen Pemmaraju, MD: Beautiful, I totally agree, and here’s what happened in the case. This patient was indeed, as Dr McCloskey beautifully outlined, put forward for the targeted agent tagraxofusp at the FDA-labeled 12 μg/kg. This is frontline therapy, and the patient did achieve a CR [complete remission] after 1 cycle of therapy. As we think about tagraxofusp, I was honored to be a part of leading this agent. As Dr McCloskey mentioned, this is a first-in-class, CD123-targeted agent. We were able to get this to FDA approval in December of 2018, published in the New England Journal of Medicine in April of 2019. Remarkably, the majority of patients who came to the study were frontline-treated patients. There was frontline, relapsed, and refractory. In the frontline setting, there was a 90% overall response rate, with a 72% CR or CRc [clinical complete response].

It’s generally a well-tolerated drug, but the only important issue to bring up is that it did have a very toxic adverse effect known as capillary leak syndrome. The capillary leak syndrome appropriately has an FDA black box warning because it’s something that can be educated [about], mitigated, prevented, and even treated. In addition to this, the FDA approval in the United States was for ages 2 and older, so it can be used in the pediatric population. Then in 2021, the agent tagraxofusp was approved by the EMA/EU, [European Medicines Agency/European Union], restricted to adults in the frontline setting.

Now, in terms of long-term benefit of tagraxofusp, our group recently published the median follow-up at approximately 3 years. That’s in the JCO [Journal of Clinical Oncology] this year. Again, with this tagraxofusp monotherapy approach, we were able to add more patients than were originally added in the New England Journal of Medicine [data report]. There are now 65 frontline patients. Out of those 65 patients with a median follow-up of approximately 3 years, there was a 75% overall response rate, with a 57% CR/CRc.

What’s probably even more important to many of the folks out there is the overall survival is shown here. Median overall survival is interesting, James. There is a tail to the curve at the data cutoff, but the median overall survival is still less than 2 years. So I guess the question for you and for the whole field is, yes, we’ve improved on the historical survival, but what are the next steps in treatment for this patient and for the field? James, what do you think about that?

James McCloskey, MD: I think that as we finish induction, we obviously want to take time to appropriately restage this person, especially as we’re wrapping up induction, to make sure we have a good quality remission. As I mentioned, this patient is in his 70s, young 70s and fit, so ideally we’re going to start looking for a donor for allogeneic stem cell transplant, which is still the goal for most of our patients. For patients who are still in that transplant process, consolidating with tagraxofusp while we’re working on that is still standard. Then we need to evaluate patients again. For some of our patients, if they have minimal residual disease or low-level disease, we might consider transitioning to another line of therapy. And off of a clinical trial, we will be watching those patients closely for early evidence of disease relapse because most of these people will relapse without an allogeneic stem cell transplant.

Transcript edited for clarity.