Sequencing Therapy in BPDCN in the Second Line and Beyond


Comprehensive insight on the sequencing of agents in BPDCN management, followed by considerations for use of stem cell transplant in this setting.


Naveen Pemmaraju, MD: I guess the question for us is this: we have a field and clinical trials going, but I still think the problem a lot of times is travel, cost—these kinds of barriers. You and I have spoken about this many times. You passionately care about this. I find you to be a great advocate for patients. James, do we need a national dedication to a rare disease like this? What’s the solution?

James McCloskey, MD: It’s a real challenge. In our institution [Hackensack University Medical Center]—we probably all feel this—we’re pushed to open trials we can accrue to, especially in the current environment, because we have limited staffing. As someone leading a division, it’s hard to say I’m going to open a trial with 2 people and that we’ll be happy about it if we’re participating with multiple other sites. First, the important thing is communication. The last person I had met with you in Texas. She went to Harvard [Medical School] and met the folks there. At the end of the day, everyone had a slightly different take. She ended up getting standard care with us. It was a lot for her because this is a challenging conversation. Inpatients can often feel overwhelmed. Not everyone can make it to Texas. In their 70s, a lot of patients don’t want to spend their time traveling. They want to be close to home.

The most important thing is communication. We’re lucky in this field because we have a lot of people who pick up the phone and answer emails. When there are questions, we’re all available to answer them. Sometimes that communication might connect that patient with a trial, or it might be thinking outside the box and talking about something that’s off-label but might fit better with that patient’s goals for their quality of life and their objectives in terms of their own personal care.

Naveen Pemmaraju, MD: What you say flows nicely into this next question, which we’ll ask Dr Gru to lead us on. You’ve both emphasized this multidisciplinary approach, and I think we all hold the pathology team above dermatology and hematology. General pathology is the highest and most important member of this team. Without a diagnosis, you can’t start anything, you can’t have a treatment, and you can’t have awareness. Alejandro, you built a nice program at your institution [University of Virginia School of Medicine]. I want you to comment on this. How does it work with dermatopathology? Talking to the dermatologist and the clinician, how do you coordinate things in these complex cases?

Alejandro Gru, MD: This is critical. Communication is the most important thing for these cases. When I work with my fellows, we get a case of possible leukemia cutis or 1 of these entities, someone might come in healthy, without any other symptoms. I had a patient who had just 1 little lesion on the face that looked like a basal cell carcinoma. You explain to your colleagues, you call the team and the clinician, “Listen, this patient has the equivalent of a new diagnosis of leukemia.” This patient needs to be seen right away, needs to go to a hospital right away, or needs to be seen by hematologists right away. While you’re working on your biopsy, you need to make sure you have all the right markers. Some of these markers aren’t available in all community dermatopathology labs. Some markers might be more esoteric. If you ever think about this, either consider doing these markers or sending to another referral center that might have the extra tools that you want to work with.

This disease is going to require aggressive treatment, and many times chemotherapy. Share this case with the hematopathologist who has the expertise from leukemia, who has expertise in AML [acute myeloid leukemia] and lymphoblastic leukemias. You want to make sure you have a strong interaction, you work as a team, you interact thoughts, and you have a rapid diagnosis so you can direct a patient correctly.

Once I had a case where a biopsy was sent to me with a patient who had an isolated lesion of reactive plasmacytoid infiltrate. Somebody thought they had reactive plasma cells on the skin or evidence of myeloma on the skin. Myeloma isn’t necessarily an extreme urgency like this is. With these patients, most are going to have leukemic involvement by the time that diagnosis is made. It’s critical that you communicate, especially when you’re talking about clinicians, dermatologists, or family practitioners who often do biopsies. You need to emphasize the rush need to have this patient seen by a hematologist, by an expert physician who has experience, to make sure the right work-up is done and that this is done in a timely basis.

If you remember the literature on some presentations, there was a significant delay between the first time the patient presents to the clinic and the time when a final diagnosis is made, of sometimes 4 months. These patients don’t have the luxury of having months. In a lot of these patients, if they don’t get referred promptly, they’re going to die from the disease. It’s critical that communication is the key word, in terms of the management of these patients.

Naveen Pemmaraju, MD: This is awesome. It flows nicely into the next topic, which is that the other key members of our multidisciplinary group and are the stem cell transplant folks. James, we know transplant is a curative modality in many aggressive malignancies, such as BPDCN [blastic plasmacytoid dendritic cell neoplasm]. I regularly transplant patients, but a lot of our patients are old or frail. This is 1 example of our own data set. The median age was 39 or 40 years old. We’re transplanting patients in their 70s routinely. You and I are advocates of stem cell transplant when we believe it’s curative, but there are barriers. How are you thinking about transplant in BPDCN these days, James?

James McCloskey, MD: It’s a goal for all our patients. It’s important to keep that in mind because it affects what we’re doing at the beginning. As someone who doesn’t do transplant, I always like drive this home to my transplanter. I think, “Give them the CR [complete remission], and we’ll take it from there.” But that’s not the answer. Not all CRs are created the same. We want a good-quality CR. We want to take a person through that and get them into CR in a shape so they can go to the transplant to tolerate that well.

That’s part of our job: to start working on that promptly, looking at our options for transplant and preserving their performance status. As we arrive at the door of transplant, we’re reassessing where we are. Just as we’ve seen in many other diseases, the quality of the remission is important as we start to plan transplant and the likelihood that it translates to help our patients. It ends up becoming a personal decision for many of our older patients. What’s the benefit of the transplant? What’s the trade-off in terms of toxicity? What might they sacrifice for that small benefit in some patient populations?

Transcript edited for clarity.

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