How to Recognize, Diagnose, and Treat Patients With BPDCN

Lancet Reviews the Key Treatment Options for BPDCN

During a Targeted Oncology case-based roundtable event, Jeffrey E. Lancet, MD, discussed the data behind tagraxofusp in patients with blastic plasmacytoid dendritic cell neoplasm. This is the second of 2 articles based on this event.

What is the background for the use of tagraxofusp-erzs (Elzonris) for blastic plasmacytoid dendritic cell neoplasm (BPDCN)?

Historically, because nobody knew what…category of disease BPDCN fell under for a long time, the treatments were relatively nonspecific. They could be treatments that were typically geared towards AML [acute myeloid leukemia], ALL [acute lymphoblastic leukemia], or lymphoma. All of them had a modest degree of efficacy, as many of them contain the same types of drugs. But the regimens that we typically use for these diseases have high toxicity rates, high rates of relapse because they don’t work very well for very long, and early death with less effective therapies.

Tagraxofusp then came into the picture, previously known as SL-401, and it’s considered a first-in-class CD123-targeted therapy. And it is a fully humanized interleukin-3 [IL-3]. It’s fused to a truncated form of the diphtheria toxin. As such, because the alpha chain of the CD123 molecule was the IL-3 receptor, this particular drug targets CD123 and delivers its payload into the cell once it binds with its receptor. It’s the only FDA- and EMA-approved treatment for BPDCN.1,2

We think about treatment options based upon how intensively you think you can treat your patients because most effective therapies for BPDCN are unfortunately also the most toxic, and this includes tagraxofusp. It is given as a 15-minute infusion daily for 5 days in a row every 3 weeks, and the other options may include chemotherapy like [the regimens used for] AML, ALL, or lymphoma. Tagraxofusp has emerged as the preferred therapy because of its high rates of efficacy and durability.

For the patients who are not candidates for intensive therapy or who are not thought to be healthy enough to go through treatment that may induce a fair amount of inflammation and toxicity, you can think about doing other things such as surgical excision if you have primarily isolated lesions that don’t have significant systemic involvement. Radiation therapy can be considered, but these are difficult undertakings because it’s hard to radiate systemic disease or surgically excise systemic disease, which is the case in most patients. Systemic [therapies] that we’re thinking about that are less intensive include venetoclax [Venclexta], which is a BCL2 inhibitor that has some level of single-agent activity.3 This can be used on occasion if the patient can’t get through more conventional therapy. Steroids can be used, and then supportive care is always a mainstay of any type of treatment. We think about these patients having poor performance status, very hypoalbuminemic, because [some] patients would get very sick from any treatment that might induce a high inflammatory response.

What clinical data supports the use of tagraxofusp for BPDCN?

[The data come from] a very intensive multicenter study [NCT02113982] that involved several centers who saw [relatively] high volumes of patients with BPDCN, recognizing that you can’t do a very good study with limited numbers of institutions with a rare disease.4 The study was designed as a 4-stage, single-arm study that started in a phase 1, stage 1 dose-finding scenario with 2 different doses—7 μg and then 12 μg. Stage 2 was dose expansion at the 12 μg level. Both of these stages included frontline therapy and relapsed/refractory disease. Stage 3 of the study, which was the pivotal stage, involved only frontline therapy for previously untreated patients, and stage 4 was more of an expanded-access stage that allowed us to gain more experience and understand the true efficacy of the disease with larger numbers of patients. Tagraxofusp was administered 5 days in a row every 21 days. The treatment could continue indefinitely until progression or [unacceptable] toxicity.

The key eligibility criteria were focused around performance status, organ function, and most importantly, a serum albumin that was 3.2 g/dL because of the concern of capillary leak syndrome that would be much exacerbated with hypoalbuminemia. The primary end point was the combined rate of complete response [CR] and clinical complete response [CRc], which is defined as disappearance of all lesions except for some residual skin lesions that represent the previous skin findings, whereas the CR meant absolute complete resolution of any visible evidence of skin disease. So the composite end points were CR plus CRc. The secondary end point was duration of response.

What was the efficacy seen in this study for patients with BPDCN?

The efficacy of tagraxofusp in patients with previously untreated BPDCN, which was the primary end point, was quite impressive with an overall response rate of 90% that included partial responses and stable disease. The CR plus CRc rate was 72%. These were the most clinically meaningful responses with clearance of the bone marrow, blood, and skin. [Tagraxofusp showed] a high rate of response, much higher than we would typically see with standard chemotherapy.

Based on the results of this study, tagraxofusp was approved about almost 4 years ago as the only drug indicated for BPDCN in both adult and pediatric patients.1 Although the trial did not include pediatric patients, the label does include age 2 and older.5 This is approved for both untreated and relapsed/refractory disease based on the results of the study.


1. FDA approves first treatment for rare blood disease. FDA. December 21, 2018. Accessed November 3, 2022.

2. Approval of the marketing authorisation for Elzonris (tagraxofusp). European Medicines Agency. November 13, 2020. Accessed November 3, 2022.

3. DiNardo CD, Rausch CR, Benton C, et al. Clinical experience with the BCL2-inhibitor venetoclax in combination therapy for relapsed and refractory acute myeloid leukemia and related myeloid malignancies. Am J Hematol. 2018;93(3):401-407. doi:10.1002/ajh.25000

4. Pemmaraju N, Lane AA, Sweet KL, et al. Tagraxofusp in blastic plasmacytoid dendritic-cell neoplasm. N Engl J Med. 2019; 380(17):1628-1637. doi:10.1056/NEJMoa1815105

5. Elzonris. Prescribing information. Stemline Therapeutics, Inc; 2018. Accessed November 3, 2022.