A Case of Cutaneous Blastic Plasmacytoid Dendritic Cell Neoplasm Treated With a Bcl-2 Inhibitor

May 2021 | Volume 20 | Issue 5 | Case Reports | 550 | Copyright © May 2021


Published online April 13, 2021

Andjela Egger BSa, Diana Coello MDb, Robert S. Kirsner MD PhDa, Julia Escandon Brehm MD PhDa

aDr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL
bHospital General Docente de Calderon, Quito, Ecuador

Abstract
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive primary cutaneous lymphoma characterized by transformed plasmacytoid dendritic cells that overexpress interleukin-3 receptor subunit alpha (IL3RA) also known as CD123. In addition to several therapies currently undergoing clinical trials, Tagraxofusp-erzs (Stemline Therapeutics, Inc., NY) is a single FDA-approved option available for treatment of adults and children over 2 years of age suffering from BPDCN. It was designed to target CD123 overexpression in BPDCN as a CD123-directed cytotoxin consisting of a recombinant human interleukin-3 fused to a truncated diphtheria toxin. We discuss a case of a male patient in his late 70s’ who presented with an asymptomatic rash involving the back and the right knee that initially developed as pink patches, progressed into plaques, and subsequently rapidly evolved into a tumor involving the right knee that was confirmed as BPDCN on skin biopsy and was accompanied by bone marrow involvement. Upon initiation of first line tagraxofusp-erzs therapy, the patient did not achieve improvement. However, off-label use of venetoclax (AbbVie Inc, IL and Genentech-USA, CA), a Bcl2 inhibitor currently in a Phase I clinical trial, resulted in a satisfactory clinical outcome, nearly complete resolution of a right knee tumor lesion, and deferment of bone marrow transplant. We believe that our case exemplifies the complexity of BPDCN, briefly reviews current treatment and management options that are only in their infancy and raises awareness towards success with alternative off-label therapies such as venetoclax when treating BPDCN.

J Drugs Dermatol. 20(5):550-551. doi:10.36849/JDD.5373

INTRODUCTION

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive malignancy caused by transformed plasmacytoid dendritic cells that overexpress interleukin-3 receptor subunit alpha (IL3RA) also known as CD123.1 Tagraxofusp-erzs (Stemline Therapeutics, Inc. NY) is a CD123-directed cytotoxin consisting of a recombinant human interleukin-3 fused to a truncated diphtheria toxin2 that was FDA-approved for BPDCN in 2018 for adults and children over 2 years of age.1 Here, we report a case of BPDCN recalcitrant to tagraxofusp-erzs, that responded successfully to off-label venetoclax (AbbVie Inc, IL and Genentech-USA, CA).

CASE PRESENTATION

A man in his late 70’s otherwise in good health developed an asymptomatic rash involving the back and the right knee. The rash began as pink patches that evolved into plaques and subsequently, the plaque on the right knee evolved into a tumor in the span of 3 months. Skin biopsy showed blastic plasmacytoid dendritic cell neoplasm (BPDCN). Bone marrow biopsy showed 22% blasts positive for CD123, CD56 and TCL1. Further workup was negative for systemic involvement.

The patient received 6 cycles of tagraxofusp-erzs but the skin lesions persisted. He was then started on chemotherapy regimen consisting of decitabine (antimetabolite analogue) and venetoclax (inhibitor of Bcl-2) and underwent three cycles. Skin lesions resolved and a follow up bone marrow biopsy showed normocelluar bone marrow with less than 1% of CD34 positive immature cells. Markers were negative for CD123, CD56 and TCL1 with no evidence of blastic plasmacytoid dendritic cells.

Venetoclax treatment conferred a favorable clinical response, disappearance of skin lesions and nearly complete resolution of the right knee tumor (Figure 1). Given the success of the treatment, the patient deferred bone marrow transplantation typically offered to patients with treatment-resistant BPDCN and he continues surveillance with oncology.