Clinical Research Updates for Treating Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

An expert weighs in on the latest updates in clinical research about this rare blood cancer that often manifests with cutaneous lesions.

Naveen Pemmaraju, MD, inaugural director of the BPDCN program and associate professor in the department of leukemia, division of cancer medicine at the University of Texas MD Anderson Cancer Center in Houston spoke with Dermatology Times® on the latest treatments for BPDCN.

The field of BPDCN is experiencing great changes when it comes to treatments, Pemmaraju noted. “Historically, groups around the world, including ours, borrowed from other cancer types and used what we would consider traditional, cytotoxic chemotherapy regimen. These are either acute lymphoblastic leukemia (ALL) based, acute myeloid leukemia based (AML), or lymphoma-based regimens. BPDCN is a hybrid disease that has elements of all of these in addition to a skin cancer component,” he said. While these regimens for other cancers may be temporarily effective for BPDCN and cause the disease to go into remission, Pemmaraju said they would often result in relapse. Researchers wanted to look for the next set of therapies – which include targeted therapies.

“The breakthrough was the discovery of CD-123 being 100% expressed or overexpressed on the BPDCN cells. This led to CD-123 surface target agents. There was no CD-123c agent available or approved so this was a brand-new area of research,” Pemmaraju said. He noted three of the major treatment therapies.

First, he mentioned CD-123 target therapies. “We were able to lead the first and only approved drug, tagraxofusp SL-401, which was approved by the FDA in December of 2018 for ages 2 and older,” he said. He noted that there are other CD-123 drugs actively in clinical trials such as IMGN632 which are actively enrolling in the US and Europe.

The next therapy he described was venetoclax, an oral drug BCL-2 inhibitor already approved in ALL and chronic lymphocytic leukemia. “We have shown demonstrated activity of that agent, and we are excited to combine that with some of the other drugs,” Pemmaraju said.

Finally, Pemmaraju said central nervous system (CNS) directed therapies play a role. “Cytotoxic chemotherapy that can prevent the development of BPDCN in the central nervous system or treat it if it’s already there,” he said.

These are the active and current therapies: either single agent or, more exciting, combining modalities into a total therapy approach, Pemmaraju said.

“With my group here in MD Anderson, across the country and across the world we have a formal network now of resources and clinical trials. Everything I mentioned is either available off the shelf, is commercially available as agents we can combine, or is in active clinical trials,” he explained. Pemmaraju said that 10 years ago, or even more recently, there were no active trials to examine drugs for BPDCN. “Doublet and triplet agents in combination are now being explored,” he said.

Even if patients only show cutaneous disease, BPDCN can rapidly become a deadly systemic disease, Pemmaraju said. “This is a bone marrow, blood cancer. Skin lesions have the same BPDCN tumor properties as the bone marrow. Patients can have these lesions in the absence of bone marrow or lymph node disease, and then it can rapidly progress.” It’s important to biopsy these patients before during and after therapy not just for formal clinical trials but also in standard care to see if the treatment is working or not, he explained.

Because BPDCN is so rare and historically very difficult to consider for diagnosis outside of academic centers, many patients are misdiagnosed with more common skin findings such as noncancerous skin lesions, infections, or other skin cancers such as basal cell carcinoma or an infection, Pemmaraju cautioned. But awareness is growing across medical specialties.

“Dermatologists are often the first to recognize this disease, but sometimes it’s the other way around, with dermatologists receiving referrals from other providers. The disease crosses many fields and the medical team needs to work together. We have now created this field: we have clinical trials, and we have drugs that are active and effective. We have established a world resource and referral center here at AMD Anderson. We are making progress, but there is still so much more work to be done for this rare disease,” Pemmaraju said.