Gary Schiller, MD: What is your current standard of care treatment for blastic plasmacytoid dendritic cell neoplasm?
Salman Fazal, MD: Historically, for BPDCN [blastic plasmacytoid dendritic cell neoplasm], chemotherapy has been the backbone of most of the treatments. We have used both AML [acute myeloid leukemia]– and ALL [acute lymphoblastic leukemia]–like regimens in treatment of BPDCN. However, those AML- or ALL-like regimens cannot be used for the majority of patients. When I am assessing a patient with BPDCN, I’m assessing whether patients are fit or frail. Usually, my treatment algorithm follows that assessment initially. I assess if the patients are fit. I consider 2 options. One is using tagraxofusp, which is the new drug therapy approved by the FDA for treatment of BPDCN. The other is intensive chemotherapy, which ALL-like regimens have been using in the past with success. However, although those do lead to a good response rate, the responses tend to be transient, and one has to follow those regimens with allogeneic stem cell transplantation. The treatment has been changed by the approval of tagraxofusp. I would assess looking at the eligibility criteria for the patients enrolled in the clinical trial. One of the major factors that played in terms of enrolling these patients was the serum albumin. If the patient’s serum albumin is less than 3.2 g/dL, I would not consider using tagraxofusp for those patients.
The second factor that excluded patients for the treatment of tagraxofusp was CNS [central nervous system] involvement. Patients who have CNS involvement may not consider using tagraxofusp unless someone wants to add CNS therapy along with the tagraxofusp, which has not been studied for that combination.
For the failed patients, it’s more challenging because the median age of the disease is in the late 60s. Unfortunately, that could be a significant proportion of our patients who get evaluated, and for those patients we may consider enrolling them on a clinical trial. For some patients who are very frail, we may consider just local therapy, and in that sense radiation could be a useful modality just for cutaneous involvement. We may consider using radiation or steroids for those failed patients who are not candidates for tagraxofusp or not candidates for even any intensive chemotherapy. What do you think about the second-line therapy?
Gary Schiller, MD: I view tagraxofusp as the first-line therapy. I’m certainly old enough to remember when we used ALL-like regimens, and we also occasionally used cytarabine and daunorubicin, an AML regimen, and our response rates were not particularly good. You’re right the way that you framed it, looking at eligibility criteria for the clinical trial, and those who fall outside the eligibility criteria are, in some ways, upon them is conferred a need for another therapy, and you have no choice but to go back to something older.
On the other hand, patients who have had an initial response to tagraxofusp, either alone or after allogeneic transplant, who sustain relapse, again are potential candidates for an ALL-like regimen. But response rates are not particularly good, and survival is not particularly long. Your best chance is when you’re treating patients initially. If they’ve never been exposed to the monoclonal antibody and have achieved a remission through a vincristine-based regimen followed by allotransplant, then of course you would use tagraxofusp in the second-line setting. But in the first-line setting, it would be better to go with the novel agent. It has a specific indication, and the alternatives are not particularly desirable.
Transcript Edited for Clarity