Long-Term BPDCN Data Show Potential for Durable CRs and Transplant

Greater recognition of the unique disease characteristics of blastic plasmacytoid dendritic cell neoplasm (BPDCN) has led to the development of targeted therapy and greater understanding of the treatment goals for patients who achieve remission. 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 long-term data and patient selection for tagraxofusp (Elzonris). Al-Juhaishi also discussed the application of chemotherapy including venetoclax (Venclexta)-based regimens. He emphasized the importance of preparing eligible patients for the eventual goal of allogeneic stem cell transplant (SCT) as the only curative treatment.

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This article is part 2 of a 2-part series from a Case-Based Roundtable event.

CASE SUMMARY

• A 62-year-old man was referred to an oncologist from a dermatologist​.
• He was referred initially to the dermatologist by primary care physician for progressive, persistent, cutaneous nodules that patient first noticed 3 weeks prior​.
• Symptoms: fatigue, unexplained weight loss (~11 lbs) in last couple months
• History: type 2 diabetes mellitus controlled with diet and metformin.​
• Physical examination: notable for multiple purpuric nodules (measuring up to 5 cm on arms, legs, torso). No palpable adenopathy, hepatosplenomegaly.​
• ECOG performance status: 0, but worsening due to symptoms​
• Laboratory results:
  • White blood cells: 14,000/uL
  • Hemoglobin: 8.9 g/dL
  • Platelets: 54,000/uL
  • Differential revealed 18% blasts,16% monocytes, absolute neutrophil count 1300/uL, 40% lymphocytes​
• Cutaneous lesions showed BPDCN; multiple cutaneous nodules and papules were observed over the chest and around the armpits. ​
• High-resolution CT images showed multiple pulmonary and mediastinal nodules and enlarged intraabdominal lymph nodes.​
• Peripheral blood smear: blastic cells with large and round or slightly irregular nuclei​
• Bone marrow biopsy: 40% blasts by morphology; 80% cellular marrow with interstitial infiltrate.​
• Immunohistochemistry: CD123, CD4, CD56, TCL1 positive
• Flow cytometry: CD4, CD56, CD123 positive; CD34, MPO, T- and B-cell lineage-specific markers negative
• Cytogenetics: 46 XY
• PET-CT did not demonstrate enlarged lymph nodes, spleen, or liver. Lumbar puncture did not indicate central nervous system involvement.
• The patient was ultimately diagnosed with BPDCN based on clinical and histopathological findings​.
• He received tagraxofusp 12 mg/kg as per package label (days 1-5 of a 21-day cycle) for frontline therapy and achieved complete response (CR) after 1 cycle of therapy​.

Targeted Oncology: What is the expected response to tagraxofusp in BPDCN skin lesions?

Taha Al-Juhaishi, MD: It can kick in right away, and it works very effectively.… [Multiple bruise-like] lesions and tumors are very typical. Typical treated lesions [result in residual skin abnormality not indicative of active disease]; at least in the patients I’ve treated, it almost never goes away. Some of the data [show] you can get as high a CR rate as 72%. That's in the untreated patients; if you use it in the relapsed setting, you'll get a lower rate, 40% or so.¹

What did long-term follow-up show in terms of tagraxofusp’s safety profile?

Some of the toxicity beyond the capillary leak syndrome [CLS] in the beginning [was reported]. Probably the biggest thing I would highlight is that some [blood cell] count issues can happen, mostly thrombocytopenia [in 43%], but nothing else of significance.¹

[CLS leads to]a lot of [edema, pleural effusions], declining albumin, hypotension, respiratory distress, and things like that. Two fatal events were seen with CLS with this drug. In the hospital, if you have them, just remind your staff to get the daily weights and to monitor their urine output and things like that.² We give interleukin [IL]-2 for tumor-infiltrating lymphocytes and [other therapies], and IL-2 is riskier than this. If someone comes in with volume overload from heart disease or something, they might need to be optimized.

What other regimens could be used and how does tagraxofusp compare with them?

Venetoclax with mini-CVD [cyclophosphamide, vincristine, and dexamethasone] or azacitidine/venetoclax to start with will get you far too; they are very active regimens.² [They have not been compared] to my knowledge. There are indirect comparisons. There is a study open in Houston [NCT03113643] looking at triplet therapy with azacitidine and venetoclax [plus SL-401] as frontline therapy. I think that probably will be practice changing. It's good to have a quick response, especially if you can get to an allogeneic transplant fast so you don't have to extend progression and things like that, especially if they're older.

Alternate treatment scenario​

• The patient received the hyper-CVAD regimen (cyclophosphamide, vincristine, doxorubicin, and dexamethasone).

What are your thoughts on this approach?

In this alternate treatment scenario, the patient receives the hyper-CVAD regimen. If you asked me, would I give hyper-CVAD or mini-CVD with venetoclax, I would say mini-CVD with venetoclax. Giving anthracyclines here is probably not very wise, unless you really have to. But acute lymphoblastic leukemia (ALL)–type regimens seem to be maybe more effective than acute myelogenous leukemia–type regimens.

Which patients might benefit from starting with chemotherapy?​

I think if they come into my clinic with lots of edema and I need to optimize them, I might use something else for the first cycle and then get them on tagraxofusp. [With poor cardiac function], if you want to get some more time to see how they handle fluids and optimize them more, maybe you can start and then switch.

CASE UPDATE

• In the alternate scenario, the patient achieved a CR​.
• ECOG performance status: 0​
• His family inquired about additional options for maintaining remission and patient was ultimately referred for allogeneic SCT.

What is the long-term outlook for these patients who go on to receive transplant?

There are long-term survivals with this disease that have been recorded. We have 2 big reports from Center for International Blood and Marrow Transplant Research and from the European Society for Blood and Marrow Transplantation. There is maybe around 50% curative potential with an allogeneic transplant.^3,4 We favor myeloablative conditioning, if you can get that, a total body irradiation–based regimen, like what we do with ALL, but most patients will be older. I have done 2 transplants so far. Both were reduced intensity, and they've done OK.

How do you decide to use SCT when BPCDN presents in the skin?

It can start off with the skin, and it will progress from there. Dendritic cells are still blood cells. If you’re asking “would you transplant someone with skin-limited disease,” I would argue yes because it will spread. If someone comes in with a skin-limited disease, you put them on tagraxofusp, and they respond, leaving them on tagraxofusp is a slippery slope, because once they [experience] progression [they cannot receive transplant]. I would say, if you feel like the transplant will be more morbid for that person, I would at least get a donor ready so once they start to progress, you move forward.

If they've seen both tagraxofusp and venetoclax, and are in CR, I will just take them, because then once they have progression, it’s likely nothing is going to get them into remission. I think anyone with BPDCN should receive a transplant. Anyone can get it, even if it's low disease volume.

I don't know if there has ever been a case where there's only 1 skin lesion, but just local therapies are not recommended, at least at the consensus level, so we'll still treat it systemically. You can irradiate that spot if it's bothering you, but we'll still get them on tagraxofusp, or azacitidine/venetoclax or some other thing with the goal of transplant.

[Looking at] outcomes for patients who have transplant, they do really well.^1,4 We see with extended follow-up, the durability of the response for some of the patients who don't go to transplant.

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_{DISCLOSURES: There were no known relevant disclosures.}

_References:

_{1. 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}

_{2. NCCN. Clinical Practice Guidelines in Oncology. Acute myeloid leukemia, version 2.2025. Accessed September 18, 2025. https://www.nccn.org/professionals/physician_gls/pdf/aml.pdf}

_{3. Murthy HS, Zhang MJ, Chen K, et al. Allogeneic hematopoietic cell transplantation for blastic plasmacytoid dendritic cell neoplasm: a CIBMTR analysis. Blood Adv. 2023;7(22):7007-7016. doi:10.1182/bloodadvances.2023011308}

_{4. Angelucci E, Deconinck E, Manteigas D, et al. Durable outcomes with manageable safety leading to prolonged survival with tagraxofusp for treatment-naive patients with blastic plasmacytoid dendritic cell neoplasm: updated results from a European Named Patient Program. Blood. 2023;142(suppl 1):547. doi:10.1182/blood-2023-178734}