Advances in the Diagnosis and Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) - Episode 6

Factors in Selecting Optimal First-Line Therapy for BPDCN

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Closing out their discussion on the first patient case of BPDCN, panelists consider which factors best inform the optimal selection of frontline therapy.


Naveen Pemmaraju, MD: From the clinical standpoint, and I’ll answer this for us, what do you do about the capillary leak syndrome? How do you determine what to do? Dr McCloskey was giving us a really nice overview, and is exactly right. You look at the performance status [PS] or the fitness. With the tagraxofusp agent, the baseline albumin does matter, and there is guidance for the numbers. It’s what we used in the clinical trials. You want to look at the cardiopulmonary status, the ECOG PS, and the albumin. If you have availability of tagraxofusp, as you can see, it’s an FDA-approved agent. But a lot of patients are older, unfit, or you don’t have availability, cost, or access.

So [our group] and other groups, have used ALL [acute lymphocytic leukemia]-based regimens such as the hyper-CVAD [cyclophosphamide, vincristine, doxorubicin, and dexamethasone]…regimen, and add venetoclax if you have it. Older, unfit [patients will get a] hypomethylator plus venetoclax, so azacitidine or decitabine. Other groups around the world have used lymphoma regimens, or AML [acute myeloid leukemia] regimens. There have been some varied approaches. In the pediatric setting, which I’m starting to have more experience with because we’re getting calls from all over the world, it does appear to be a slightly different disease in some of these children than the adults. As usual, they seem to be a bit more chemotherapy-sensitive. So again, you can use the tagraxofusp agent, which is approved in that setting, hyper-CVAD, ALL-based regimens, and then as James nicely mentioned, allotransplant in CR1 [first complete remission] if your patient is fit. That is just to put it out there, that there are other strategies. Then there are lumbar punctures for central nervous system disease, and maybe a consideration of maintenance after.

I think we’ve talked about this already, but I want to get your take. One question to ask on the tagraxofusp, SL-401, or Elzonris, James I’ll ask you, what are your impressions 3 or 4 years later? We have this drug, we have a feel now, and we have discussions like this. What do you think, what’s the future for BPDCN [blastic plasmacytoid dendritic cell neoplasm] and this drug?

James McCloskey, MD: I think this is an exciting new agent in this field. More than anything, having a drug that’s specifically approved for this disease, the only drug approved in this disease, has raised awareness. I think that’s one of the reasons a lot of people are highlighting it and talking about it, because we treat it differently now. Not everyone gets induction therapy with multiagent chemotherapy.

In this older patient population we saw in this study, which really represents your day-to-day patient with BPDCN, these are impressive CR rates, and they appear durable for some patients. Most of these patients are going to relapse, but they do appear to be CR rates that look superior to what we’ve seen historically with chemotherapy in older patients. Again, particularly in these elderly patients, it can be hard for those patients to tolerate full-dose hyper-CVAD. So I think there are a lot of other exciting therapies in development. As we start to borrow from drugs approved in AML that might have even more favorable toxicity profiles for elderly patients, that will be an exciting option. Figuring out how to maintain these patients in a remission once we get it is key.

Naveen Pemmaraju, MD: That’s great. The final question for this case, I’ll address for us, which is are there other adverse events? We mentioned the capillary leak syndrome: potentially fatal, black box warning, 18% to 20%, you need to know about that. The second and third issue are usually all restricted to cycle 1. On the study and in the real world, we do see thrombocytopenia in about half the cases, and increased in LFTs [liver function test] levels, AST [aspartate transaminase] and ALT [alanine transaminase] in particular. Usually its restricted to cycle 1, the first 3 to 5 doses, and then very rarely after that do you see any of these toxicities. Interestingly, we do not see very much neutropenia or neutropenic fevers, so it’s not a cytotoxic agent with hair falling out, or a lot of nausea and vomiting. That’s important.

I usually do admit patients. I admit them for the first cycle for sure, you have to do that. Watch out for the capillary leak, albumin. I also usually end up admitting most patients for subsequent cycles. Of course, you can do this as an outpatient treatment. Watch that albumin. Then you don’t have to do all 5 doses, days 1 through 5, in a row. It’s built in that you can take a break. Look to see if there’s too much weight, then you can do diuresis. I think these are important. I’m proud to tell you that what’s on the package label insert is basically what we did on the trial, so maybe have a pharmacist and a health care team following the patient with you.

Transcript edited for clarity.