What dermatologists should know about blastic plasmacytoid dendritic cell neoplasm

Expert who has devoted a career to research shares insights

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare acute leukemia sub-type that often first presents with skin manifestations. In fact, dermatologists are among the doctors most likely to see these patients before they’ve been diagnosed, according to Naveen Pemmaraju, M.D., a hematologist-oncologist and associate professor in the department of leukemia at The University of Texas MD Anderson Cancer Center, Houston.

Dr. Pemmaraju led the definitive study published in April 2019 in the New England Journal of Medicine1 that ultimately helped to lead to the U.S. Food and Drug Administration’s (FDA) approval of tagraxofusp (Elzonris, Stemline), the first targeted therapy specifically indicated for patients with BPDCN.

The FDA approved tagraxofusp in December 2018 for the treatment of BPDCN in adults and children ages 2 years and older. BPDCN highly expresses interleukin-3 receptor alpha unit (CD123), and the drug tagraxofusp directly targets CD123 (IL-3R), according to the Leukemia and Lymphoma Society’s BPDCN factsheet.2

“In 29 first-line patients who received the optimal dose of [tagraxofusp] in the pivotal trial (12 mcg/kg/day), the overall response rate was 90%, with a 72% rate of complete response (CR) plus complete response with minimal residual skin abnormality (CRc). Of these patients, 45% were successfully bridged to [stem cell transplant] SCT,” according to the Society’s fact sheet.

Researchers have found that BPDCN is a complex disease that can involve three major compartments including bone marrow disease, lymph node disease and skin disease, and is a leukemia of plasmacytoid dendritic (pDC) cells, according to Dr. Pemmaraju.

“That discovery led to the understanding that whether there are skin lesions or not, this is a systemic disease that generally requires systemic chemotherapy or immunotherapy approaches, not just localized approaches. And then if you’re young and fit, a bone marrow transplant ideally in first remission appears to be indicated for those patients in which this is feasible,” he says.

Dr. Pemmaraju, who is part of a small worldwide group of dedicated scientists and clinicians that are trying to build BPDCN awareness among dermatologists, primary care and emergency physicians, pediatricians and others recently sat down with Dermatology Times to discuss what dermatologists need to know about BPDCN.

DT: What should dermatologists look for and what should they do when they suspect BPDCN?

Dr. Pemmaraju: The vast majority of patients, two-thirds or more, present with skin manifestations. That means a cutaneous lesion is oftentimes the sole manifestation or it develops over time. The problem is that when only skin-directed or localized therapies have been used, outcomes have been abysmal in the majority of patients.

Skin lesions of BPDCN appear to have a characteristic presentation. They’re usually dark purplish type lesions. They can be maculopapular but usually dark purple is one of the key presentations in the clinic. I would say clinically there is a somewhat distinct look, although I would add the caveat that these lesions act heterogeneously. One must involve their dermatologists and dermatopathologists early on in the workup to start thinking about diagnosing and confirming BPDCN. It is a true multi-disciplinary approach that is best.

The only way dermatologists and others on the frontlines are they’re going to know whether it’s BPDCN is with a biopsy. ‘Tissue is the issue’ as they say. If something looks irregular, abnormal and if it’s clinically indicated, a biopsy is really what you need to do. A lot of these patients get mistaken for other diseases, infections, other cancers. I think that’s important.

Next, you really need expert review. What we found is these cases have a certain profile. Think 1,2,3,4,5,6. That’s CD123, CD4, CD56 as sort of the golden triad. Now we know there are other markers, TCL1, TCF4, CD303 and others. When you put together these three to six markers, it helps you distinguish BPDCN.

Anytime you have a rare disease there is an expectation that these diseases are so rare that there are no treatments for them. Now we have this first FDA-approved therapy, and there are now multiple clinical trials in development. If you look on ClinicalTrials.gov, you’ll see that my group and several other groups have several other ongoing clinical trials for this disease.

The dermatologist and dermatopathologist roles are so important. As we educate our fellow hematologists/oncologists, we must continue to educate dermatologists many of whom are going to see this disease for the very first time in the clinic before anybody else. I believe it will start to appear on dermatology and derm-path board exams soon.

Dermatologists are partners to me. If you look on the New England Journal paper, Madeleine Duvic, M.D. was a coauthor. She’s a dermato-oncologist here at MD Anderson Cancer Center. On these new clinical trials, we try to collaborate with our dermatologists and dermatopathologists on the clinical diagnosis but also to pioneer research.

BPDCN is a unique disease in the leukemia/hematology oncology space because the differential for conditions involved with the bone marrow and skin is actually quite a small list. But BPDCN should be prominently listed there. Now it’s on the World Health Organization (WHO) 2016 re-classification for pathological bone marrow diseases as its own category under myeloid neoplasms, and it should be considered for inclusion in dermatology society guideline considerations for diagnostic workup.

Disclosures:

Dr. Pemmaraju has ties, including consulting, research, honoraria, grants or travel reimbursement with Pacylex Pharmaceuticals, Affymetrix, Inctye, Novartis, LFB Biotechnologies, Stemline Therapeutics, Celgene, AbbVie, MustangBio, Roche Diagnostics, Blueprint Medicine, DAVA Oncology, Samus Therapeutics, Cellectis, Daiichi Sankyo and Plexxikon.

References:

1 Pemmaraju N, Lane AA, Sweet KL, et al. Tagraxofusp in Blastic Plasmacytoid Dendritic-Cell Neoplasm. N Engl J Med. 2019;380(17):1628-1637.

2 Facts about blastic plasmacytoid dendritic-cell neoplasm (BPDCN). Leukemia & Lymphoma Society website. https://www.lls.org/sites/default/files/National/USA/Pdf/Publications/FSHP2_BPDCN_FINAL_2019.pdf. Updated July 2019. Accessed August 2020.