North American Blastic Plasmacytoid Dendritic Cell Neoplasm Consortium (NABC) Publishes Position Statement for BPDCN

To address the current state of BPDCN treatment and identify areas for future research, a group of hematologists, oncologists, stem cell transplant physicians, pathologists, dermatologists, and pediatric oncologists formed the North American BPDCN Consortium (NABC) in October 2021. The NABC has released a 44-page position statement from its inaugural meeting that includes standards of care and areas of need for BPDCN. Naveen Pemmaraju, MD, associate professor in the department of leukemia, division of cancer medicine at the University of Texas MD Anderson Cancer Center in Houston, and 58 pediatric and adult experts from a variety of fields participated in authoring the statement.

The NABC said the 2 main goals of the document were, “to describe the US/North American standards of care for diagnosis, management, treatment options and approaches for patients with BPDCN [and] to identify urgent areas of unmet medical need representing touchstone points for future directions in research, drug development, and innovations in the BPDCN field.”¹

The Consortium identified 10 standards of care in newly diagnosed patients. First, they addressed uniform diagnostic approaches. They emphasized a “multi-disciplinary approach with incorporation of upfront consultations with leukemia or hematology-oncology, HSCT, dermatology, and close collaboration with expert pathology (dermatopathology and hematopathology when accessible).”¹ They included a 12-step list of initial workup protocol. They then described the importance of differentiating BPDCN from other diseases, such as varieties of acute myeloid leukemia, that mimic BPDCN or look similar. Researchers noted that BPDCN is “its own unique clinical entity.”¹

Next, the authors addresst reatment. They emphasized systemic therapy as a first approach and the important role of CD-123 targeted agents. They explored the use of venetoclax (BCL2-antagonists) and cytotoxic chemotherapy multi-agent regimens. They also suggest using central nervous system (CNS) prophylaxis as a new care standard, and they discuss the role of hematopoietic stem cell transplantation (HSCT) in first complete remission (CR). NABC then described the current approach to frontline treatment, followed by the importance of clinical trials.

The next section explored areas of need for BPDCN, First, the authors highlighted the need to broaden education and awareness of BPDCN. “We recommend the continued inclusion of BPDCN in all World Health Organization (WHO) editions, all malignant hematology panels/guidelines, hematology board reviews/exams, hematology/oncology fellowship curricula, along with increased efforts to publish BPDCN research in journals worldwide,” they said.

Other needs include making measurable residual disease (MRD) standard in BPDCN, which authors said was one of the highest priority issues that are not yet met. Another need is to remove HSCT for BPDCN due to most patients being older, having multiple comorbidities, and not being fit for that treatment. Instead, NABC recommended more focus on increased MRD testing and combination therapies. The authors said the development and standardization of combination therapies is another area that needs attention. BPDCN’s “underlying/unifying disease pathobiology/pathway” also need to be identified, the authors said.¹

Pediatric BPDCN needs more research both to distinguish it from adult BPDCN and to increase safe and effective therapies for children. Authors noted “the lack of pediatric-focused BPDCN clinical trials and barriers to inclusion of pediatric patients in trials.”¹ Patient quality of life outcomes also need more attention.¹ NABC also said prognostic markers and risk stratification need to be developed for the disease. They recommended that all BPDCN patients be offered places in clinical trials. Finally, they noted the importance of compiling sources of funding for BPDCN research, such as philanthropy, grants, and foundations. They noted the difficulty of fundraising for rare diseases, and that costs for targeted therapies may prevent their use.

“We call for greater emphasis on rare diseases and rare blood cancers in general, and advocate for specific grant opportunities to support research for BPDCN. The NABC concluded with a reminder that discoveries in the rarest disease states, oftentimes rare blood cancers, have subsequently led to breakthroughs in other, more common entities, thereby ultimately helping even more patients over time,” the NABC concluded.¹

Reference

1. Pemmaraju N, Kantarjian HM, Sweet KL, et al. North American Blastic Plasmacytoid Dendritic Cell Neoplasm Consortium: position on standards of care and areas of need [published online ahead of print, 2022 Nov 18]. Blood. 2022;blood.2022017865. doi:10.1182/blood.2022017865