Targeted Therapy for BPDCN Provides Path to Allogeneic Transplant

Patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) have limited treatment options but can have good outcomes if they can achieve a remission and receive allogeneic hematopoietic cell transplant (HCT). As moderator for a Case-Based Roundtable event in Dallas, Texas, Taha Al-Juhaishi, MD, associate director of the Hematopoietic Stem Cell Transplantation and Cell Therapy Program at OU Health Stephenson Cancer Center in Oklahoma City, discussed the regimens that present the best opportunity to reach complete remission, including established chemotherapy regimens and the targeted therapy tagraxofusp (Elzonris). Al-Juhaishi shared his own experience getting patients to allogeneic HCT, using CD123-targeted therapy, and managing the early toxicity associated with this treatment.

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What therapies can be used to treat BPDCN?

Taha Al-Juhaishi, MD: The NCCN has guidelines for how to treat this disease.¹ I can start by saying there's no standardized treatment for this disease, so different people will do different things. But there are 3 things to remember. No. 1 is starting with a targeted therapy for CD123, despite some capillary leak and some other risks initially that you can run into. At least my experience with it, it’s a very effective, very easy-to-handle therapy for older people, if you can get them through the capillary leak risk in the beginning. Most places would start with that or some combination that includes that.

The other option that has been historically effective is acute lymphoblastic leukemia–type of therapies. I wouldn't say hyper-CVAD [cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride (Adriamycin), methotrexate, and cytarabine], because most [patients] will not be candidates for hyper-CVAD, but some mini-CVD, or some form of that is also an effective option. The last thing I'm going to say is venetoclax [Venclexta] is a very active drug in this disease. In fact, my last 2 transplants with this disease…both got into remission enough to do a transplant with a venetoclax-based regimen. These are the 3 things I would highlight about the treatment.

How should you proceed in patients whose disease responds to treatment?

Once you get some disease control, it's a very easy decision, at least here in the United States. If it's a complete response, and they're fit enough to do an allogeneic HCT, you should do an allogeneic HCT. If not, the systemic therapies can probably at least extend the survival by up to 2 years with all the sequencing of these regimens.

There are some data for autologous HCT. It's not very well established, at least here in the US. We've never done that. I don't know if any center in the US would do an autologous HCT. In Europe, they might. My patient is now 1 year out from an allogeneic HCT. It took 3 lines of therapy to get into an allogeneic HCT between relapses and no donor. He's doing phenomenally. I have another one at 6 months or so, and then 2 or 3 other [patients] treated who [died]; unfortunately, they were also older patients.

It is a very aggressive disease. Once it's not controlled, it will move very fast. You can irradiate the skin. I have irradiated those patients in some spots that were persistent before the transplant. Radiation works very well, but most of the time they have extensive skin involvement [you cannot] irradiate.

What data supports the use of targeted therapy for BPDCN?

This is the targeted therapy, and it's a very interesting drug, tagraxofusp. It's a diphtheria toxin bound to the targeted therapy to CD123, which is an IL-3, essentially. The drug is given intravenously daily for 5 days in a row every 21 days. It's been approved since 2018, so it’s been available for 5 to 6 years. If you look at the totality of evidence, you have a response rate above 50% including complete response of 50% just by itself, without having anything else along with it.² I remember a patient where I treated this big lesion after 1 or 2 doses while still in the hospital for the first cycle; it was shrinking by the time he left the hospital; by day 5, it was most of it is gone. It’s like a true targeted therapy that kicks in right away.

What is the tolerability challenge with tagraxofusp?

The issue with it, there are some eligibility criteria about albumin and things like that, because of capillary leak syndrome that has been seen with this drug. It’s started in the hospital, because patients are older and we worry in the first cycle, most of the significant capillary leak happens within the first cycle or 2. Especially if you haven't used the drug a lot, to keep it on the safe side for everyone involved, we've done it always in the hospital to begin with.

We always get a push back from the hospital. In our hospital, we have the cancer center, and then we have the hospital people, but we're all under the university, and there is a lot of back and forth, and then someone will figure out a way to get the drug from the cancer center, where it is an outpatient drug, to be given in the inpatient unit.

My total exposure is 7 or 8 patients, but if you look at the trials there are [patients] who have died in the studies from capillary leak. The risk of capillary leak is less than 20% and the risk of grade 3 or 4 is less than 10%.² It's 5% to 7% so if you're very proactive, you're monitoring your albumin, you're giving them steroids, holding the drug, [use diuretic], I think you'll be OK. Our last 2 patients had zero capillary leak and responded.

I usually take them to an allogeneic HCT if I can after 3 or 4 cycles, usually how long it takes to find a donor and get everything ready too. But if you're not taking them to an allogeneic HCT, you should continue to progression, and the majority will eventually progress on this too.

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DISCLOSURES: There were no known relevant disclosures.

REFERENCES:

1. NCCN. Clinical Practice Guidelines in Oncology. Acute myeloid leukemia, version 2.2025. Accessed August 26, 2025. https://www.nccn.org/professionals/physician_gls/pdf/aml.pdf

2. Pemmaraju N, Sweet KL, Stein AS, et al. Long-term benefits of tagraxofusp for patients with blastic plasmacytoid dendritic cell neoplasm. J Clin Oncol. 2022;40(26):3032-3036. doi:10.1200/JCO.22.00034