An Overview on Blastic Plasmacytoid Dendritic Cell Neoplasm and Tagraxofusp Therapy


Expert hematologist-oncologists share their perspective on the broad diagnosis and management of blastic plasmacytoid dendritic cell neoplasm (BPDCN).


Thomas Leblanc, MD: Welcome to this CancerNetwork® Between the Lines program. Today’s featured article is, “Long-Term Benefits of Tagraxofusp for Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm [BPDCN].” That’s always quite a mouthful. I’m Dr Thomas Leblanc from the Duke Cancer Institute’s acute leukemia program [Durham, North Carolina], and I’m happy to be here to discuss this publication with my colleague, Dr Patel, and I’ll let her introduce herself briefly.

Bhumika Patel, MD: Hi. My name is Dr Bhumika Patel. I’m from Prisma Health Cancer Institute in Greenville, South Carolina, and I look forward to having a great discussion with Dr Leblanc about the long-term benefits of tagraxofusp in BPDCN.

Thomas Leblanc, MD: Wonderful. Why don’t we get started by talking a bit about what BPDCN is. Tell me how you make this diagnosis.

Bhumika Patel, MD: I think what’s interesting about BPDCN is due to its rarity there is the challenge of diagnosis. One of the primary diagnostic features of BPDCN is a skin manifestation. We have a lot of skin manifestations in a dendritic cell-derived myeloid neoplasm that we do worry about in patients. That is one of the main manifestations of this disease, but you may have patients with marrow involvement, lymph node, and extramedullary disease. I think getting a good biopsy, and working with your hematopathologist and dermatology would be imperative to get a diagnosis of BPDCN.

Thomas Leblanc, MD: It’s been really interesting to see this diagnostic category evolve over the years; 10 or 15 years ago there wasn’t such a thing. There were some different names and terms for this disease, but we have come to learn now that it can present in diverse ways too. I sometimes see patients who have only skin involvement, and these lesions can just look like bruises, these kind of purplish or black colored looking spots, and often these patients go undiagnosed for a while, especially if they don’t have marrow or peripheral blood involvement. As you just pointed out, some of them don’t have any involvement other than the skin, so you have to think about it and suspect it. Then, [the biomarker] CD123 becomes important because that’s a critical piece of what has to be present to clinch this diagnosis, and that will lead us into some discussion later about tagraxofusp because it targets that particular epitope. What’s your sense, Dr Patel, for prognosis with this rare disease?

Bhumika Patel, MD: The prognosis for BPDCN, it’s a rare entity, as we know it makes up less than 1% of the myeloid disorders that we have, but I think the prognosis for this based on the meta-analysis and data that have been published—it’s less than 2 years overall survival. I think that’s where we need better therapy, such as tagraxofusp and other therapies we have in our arsenal, and clinical trials to better address these patients with BPDCN and take care of them on a multilevel approach, so we can take good care of them and improve their overall survival.

Thomas Leblanc, MD: Absolutely.

Bhumika Patel, MD: Dr Leblanc, according to the National Comprehensive Cancer Network[NCCN] guidelines, when you have a newly diagnosed patient with BPDCN, after appropriate diagnostics have been completed, what are some of the treatment options you would give? What do you consider when you consider intensive therapy versus nonintensive therapy based on clinical presentation?

Thomas Leblanc, MD: This is an area where thankfully things have changed positively in this disease in just the last couple of years with the approval of tagraxofusp. Historically, we haven’t had a great sense of how we should be treating this disease, and if you look at the literature there’s a whole range of therapies and classes of therapies that have been used. What I mean by that is a number of studies used AML [acute myeloid leukemia]-type induction therapy, like an intensive induction type of chemotherapy, the 7 plus 3 type of regimen. But then there’s also literature suggesting that more of an ALL [acute lymphocytic leukemia] type therapy can be effective or maybe more effective in this disease. That would be something like the hyperCVAD [cyclophosphamide, vincristine, doxorubicin, dexamethasone] regimen. There also even is some evidence about using lymphoma-type induction regimens like the CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone] regimen that we use commonly for DLBCL [diffuse large B-cell lymphoma] and even some T-cell non-Hodgkin lymphomas.

So it’s been all over the map, but now with tagraxofusp, this is clearly the preferred, recommended therapy per the NCCN guidelines. When we get into talking about this article in a few moments it becomes clearer why around the efficacy rates here. The other piece though that’s important to underscore and to remind everyone about, if they don’t already know, is that there is a significant risk of CNS [central nervous disease] disease with BPDCN. Patients should be screened for CNS disease up front, and they should receive intrathecal chemotherapy as prophylaxis just like we would do with an acute lymphoblastic leukemia kind of regimen. That’s particularly important to help optimize the outcomes of these patients. Dr Patel, what about relapsed or refractory kinds of patients? What have you seen or used in that setting?

Bhumika Patel, MD: I think in the relapsed/refractory setting in BPDCN, we know the median age of diagnosis for these patients is around 65 to 70. When they’re relapsed/refractory, always look at their performance status to decide what treatment options may be available. But I always look at clinical trials as a first option because there are a lot of great studies coming down the pipeline that are being evaluated, like looking at targeted therapies such as venetoclax-based regimens and even looking at CAR [chimeric antigen receptor] T-cell therapy targeting CD123. I would definitely recommend my patient go to an academic center, coming from a community setting. If I have a relapsed or refractory patient, I would discuss it with colleagues such as yourself, and ask, "Do you guys have any trials for BPDCN?” And if the patient is fit enough to go through that, then consider piggybacking once in complete remission from that therapy, in the second line I would recommend to try to get them to an allogeneic bone marrow transplant to improve their overall survival.

Thomas Leblanc, MD: Yes, absolutely. Transplant is critically important in this disease to optimize long-term outcomes if it’s at all possible for any particular patient. Unfortunately, sometimes patients aren’t transplant candidates, or despite our best efforts things happen and they don’t end up being able to get there, but that needs to be the goal for many or most patients with this disease. The other thing to mention about relapsed or refractory disease is now the NCCN guidelines include a recommendation to consider venetoclax-based therapy, in part because there have been some recent data suggesting that that can be an effective salvage kind of a therapy option for patients with BPDCN, but it’s not something that’s generally recommended for upfront therapy at this point. The recommended therapy is tagraxofusp up front. Can you talk about how this drug works and what the rationale is for using this in BPDCN and what the FDA indication looks like?

Bhumika Patel, MD: Tagraxofusp is approved in the front line for patients with BPDCN that’s diagnostic, and it is targeted therapy for CD123. I think this is one of a kind in its arena because it’s a targeted therapy. We are trying to make sure that these rare entities get more targeted therapy because it’s expressed in the BPDCN cells. It is a targeted therapy for CD123. In the United States it’s approved up front after age 2, and it’s approved in the European Union for adults with BPDCN. It’s a targeted therapy, which makes it really exciting, I would say, in this arena because we don’t have targeted agents for this. And as you mentioned, venetoclax is being studied in the relapsed/refractory setting, so I think that will tell because we know BCL2 is highly expressed in patients with BPDCN also. Targeted therapies are the new way to go because we know the overall outcomes for these patients outside of targeted therapies are not as optimal as we would like them to be.

Thomas Leblanc, MD: Yes, that was very well said. One of the unusual things about this therapy is that it includes basically diphtheria toxin attached to the monoclonal antibodies, so it brings this toxic substance that you couldn’t give in a meaningful amount in a person’s peripheral blood. But it delivers it in a small amount as basically a toxic payload just to these CD123-expressing BPDCN cells, and that seems to be part of the magic of why this therapy is so much more effective than what we would have done historically. But it also leads to some significant toxicities, with capillary leak syndrome from the diphtheria toxin, and we will talk about that in a few moments too.

Transcript edited for clarity.

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