Advances in the Diagnosis and Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) - Episode 7

Patient Case 2: A 22-Year-Old Woman With BPDCN

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Expert panelists review the case of a 22-year-old woman diagnosed with BPDCN and consider the role of first-line chemotherapy in this setting.


Naveen Pemmaraju, MD: Gentlemen, let’s move into case number 2. Very exciting discussion so far, I’m actually learning quite a bit from both of you. This is a 22-year-old female. She presents with bulky lymphadenopathy and some skin lesions. They’re maculopapular in nature, across the face and trunk. Initially, it was thought to be that maybe she was going to have ALL [acute lymphocytic leukemia] or lymphoma, but then bone marrow shows 48% blasts. CD123-positive 456, and one of the new markers, TCL1, and TCF4 all positive. I can tell you this patient had classic newly diagnosed BPDCN [blastic plasmacytoid dendritic cell neoplasm]. Interestingly, because it was a young female, BPDCN was not on the radar, thinking that it should be an older male disease. As both of you mentioned, awareness is the key.

So young female, BPDCN diagnosis. I wanted to turn it to Dr [Alejandro] Gru again. I really think this is important, what you both said, about the awareness model and algorithms. Dr Gru, you get so many cases. How is somebody supposed to think about a rare disease when it’s not even the right demographic? What are your thoughts on that? How do we train our fellows and our staff to recognize this?

Alejandro Gru, MD: I think those are excellent questions, and you’ve made some excellent points. In a young patient that has perhaps multiple skin lesions, multiple skin nodules, the first thing that is going to come to mind¼if I’m thinking about someone who has blasts in the bone marrow, it’s going to be a lymphoblastic leukemia. That is usually going to be the most common diagnosis we’re going to find. Just a few weeks ago I had a child where the skin biopsy was the first time that he was diagnosed with the B cell-ALL, and then we immediately have to send the patient to the ER [emergency room] to have him further evaluated. So understanding that this disease is not restricted to adults: There are 2 main peaks. There is a peak that happens between the age of 70 and 80 years of age, but there is also a peak that happens in younger patients. Sometimes you can even see patients who are less than 10 years of age. So that’s number 1.

Number 2, it is important to understand that some of the immature markers that you see in lymphoblastic leukemia, that sometimes present on the skin, can also be seen in BPDCN. For example, TdT, which is a prototypic marker seen in lymphoblastic leukemia—either B- or T-cell lineage—is seen in a proportion of cases of BPDCN. About 30% to 40% of cases. It’s interesting, if you look at the literature, perhaps those might even be cases that do better prognostically than conventional BPDCN cases. So it is important to have that in mind.

Another thing that is also interesting is that some cases of BPDCN do not have that classic blastic morphology that you see with more common acute myeloid leukemias [AML] or acute lymphoblastic leukemias, where we would have blasts that are intermediate size and have fine chromatin, but actually they will have an immunoblastic appearance. And this is a variant that is rarely seen here in the United States, but it was actually described by the Japanese team. They have this immunoblastic morphology resembling a diffused large B-cell lymphoma, and these cases have a MYC translocation similar to what you see in other entities, similar to if you saw B-cell lymphoma or Burkitt lymphoma. So I think it is critical when you have a young patient with multiple skin lesions, something that look like blasts, that you go over your differential, thinking about the most common things, which is the lymphoblastic leukemia lymphoma, but also still keep this rare disease in your differential to make sure you do an accurate immunophenotypic evaluation in the biopsy.

Naveen Pemmaraju, MD: Wonderful. So building on those nice comments you laid out for us, the diagnosis was confirmed as BPDCN. Now, turning to James, the team was unable to acquire the CD123 agent for various reasons. The patient was dutifully treated with hyper-CVAD-based chemotherapy and got her LPs [lumbar punctures] done. She also achieved complete remission after the part A and part B. Just to remind people, methotrexate–Ara-C (cytarabine) is the part B, as you and I are well aware. Now the question for you is shown here. We’ve had 2 nice cases, an older fit person, a younger fit person. Two pretty different programs, both achieving CR [complete remission]. Here’s the million-dollar question for you and me, James. How do you choose between an older and a newer regimen? There’s not going to be any randomized control data in these small groups. What are you doing in your practice? Is it basically individual situations, tumor bulk, age, are you trying to get to a transplant? What are your thoughts on that?

James McCloskey, MD: It truly is incredibly challenging. I think we’re all fortunate for the work that you’ve done, because some of your retrospective data looking at the outcomes of patients have been helpful. First and foremost, we should point out that this is a young woman who, honestly, was not well represented by the patients who enrolled on to the clinical data we have with Elzonris (tagraxofusp). The median age there was around 72 in the first 3 cohorts. The youngest patient was really in their 40s. So she’s a challenging patient. We don’t have a lot of concrete data to go upon. But some of the retrospective data out of [The University of Texas] MD Anderson [Cancer Center] have really shown that these younger patients, as you alluded to earlier, do seem to be more chemotherapy-sensitive. Additionally, these are patients who typically tolerate multi-agent chemotherapy at the full dose.

For us, I think, this is a lady who has bulky lymphadenopathy. Certainly, there is an appeal, in my opinion, in getting drugs that really penetrate the CNS [central nervous system] as well. Especially if we think of this as a reservoir for possible relapse. So these young patients, while there is still some gray area in terms of the best treatment, are folks whom we might look at as more suitable for multi-agent chemotherapy as a bridge to transplant.

Naveen Pemmaraju, MD: Wonderful. This brings us to that question about toxicities, as you nicely mentioned. That’s certainly a part of what we think about. You may have a patient with some mild or major cardiopulmonary abnormalities or albumin issues. That may steer you away from the CD123 therapy. Bulky lymphadenopathy may be a concept of you wanting immediate tumor debulking in an emergent situation. Proliferative white count, maybe that steers you towards cytotoxic. I really love that.¼[And] just to remind people, I am admitting patients for hyper-CVAD-based chemotherapy for induction and really for the subsequent cycles. As you would do in a high-risk ALL. Watch out for tumor lysis syndrome, watch out for infections and sepsis, watch out for myelosuppression. So here it was cytotoxic effects. Also, what’s the performance status [PS] going to be, James, heading into the stem cell transplant? One of the advantages with the tagraxofusp has been people maintaining their PS. Have a good team, follow those labs, inpatient and outpatient, closely. Any fever, go to the emergency room. Good ALL, AML management in that setting is important.

Transcript edited for clarity.