Centering discussion on the third patient case, panelists review second-line therapy options for those who relapse with blastic plasmacytoid dendritic cell neoplasm.
Naveen Pemmaraju, MD: Great discussion thus far. Let’s go to our third, and I believe our final, case for this program. This is going to be a little bit more of a real-world situation here. We have a progressive disease situation. This is a 57-year-old man who has confirmed BPDCN [blastic plasmacytoid dendritic cell neoplasm], very good ECOG [Eastern Cooperative Oncology Group] performance status of 1. In this case, [he] received yet another different regiment, an AML [acute myeloid leukemia]-based standard 3 plus 7 regimen, as a frontline approach. Initially, while he did achieve a complete remission, a CR1 [first complete remission], this was found to be only less than 6 months so it was deemed to be an important case of an early-relapsing patient.
This patient presents to you in clinic with good performance status, good discussion, and not a whole long list of standard therapies. You discuss certain options such as tagraxofusp, clinical trials, further chemotherapy, venetoclax, hypomethylating agents, all the things that we talked about. The first question for Dr [Alejandro] Gru is actually an important question that I was looking forward to asking you. Sometimes we notice our patients with BPDCN will respond in one compartment but progress in another. [For example,] a bone marrow response but the skin is coming off, or the skin response but a lymph node is growing, and the biopsy is clearly showing BPDCN.¼ What are your thoughts, what are you thinking about? Are these different sanctuary sites? Is this the same disease? Is it spread out all over the place? How come if it responds in one area, Alejandro, it doesn’t in the other? What are your thoughts there?
Alejandro Gru, MD: This is a very interesting and a very peculiar question that keeps us awake all night trying to understand why this happened. What is interesting is, I think there’s been some molecular data that if you look at different sanctuaries, you’re going to see a somewhat similar base of molecular alterations at the genetic level, looking at copy number changes or looking at mutational profile. When they start on the skin and they progress into the bone marrow subsequently, sometimes you see the acquisition of new copy number changes, new mutations, etc., that were not seen before.
I will say this is very interesting because we had a recent case where the patient had bone marrow disease and had skin involvement, both showing a similar BPDCN-like phenotype. Interestingly, there were some peculiar differences in the molecular landscape. There were some differences in the copy number changes, one has more copy number alterations than the others. So it is critical, and what you say is actually true, that it is very likely that perhaps different compartments might show evolution of different levels and might gain or lose certain alterations that make the tumor more suitable to grow in that environment but not in the other. Perhaps the chemotherapy, or targeted therapy, can actually target well in one area, but not necessarily well in the other. [The disease] might acquire subsequent alterations that make it less responsive to that. I think that’s an area that it’s so difficult to evaluate given the rarity of the disease. It’s so critical to have enough cases where you analyze biopsies at different time points in life, and trying to understand why there is progression in one place and not in the other. But I think that’s a fascinating question, and that is something that is really going to help to direct treatment to these patients.
Naveen Pemmaraju, MD: That’s awesome. It’s exactly the scenario we face. I didn’t put it in the description, but that’s exactly what happened, there was some progression and mixed response. We had a discussion, and the decision was discussed [if it should be] clinical trials, again with the IMGN632, which now known as pivekimab sunirine. The patient opted for standard of care, [and] in that case, there’s only one left, tagraxofusp, which the patient did not yet have in the front line.
Transcript edited for clarity.