Relapse of tagraxofusp treated blastic plasmacytoid dendritic cell neoplasm with loss of CD123 expression

Rohit Gulati,Tareq Salous,Mehdi Nassiri,Asma Abu-Salah

doi:10.1007/s12308-021-00479-z

Abstract

Tagraxofusp, a CD123-based-targeted immunotherapy, was recently approved to treat blastic plasmacytoid dendritic cell neoplasm (BPDCN) with excellent response. Also, a subset of BPDCN shows resistance to tagraxofusp. These resistant cases continue to express CD123, which forms the basis of the continued utility of tagraxofusp in newer combination chemotherapies to overcome resistance in BPDCN. Herein, we report a case of an elderly male with BPDCN that achieved complete remission on initial primary treatment with tagraxofusp. However, BPDCN relapsed after 1.5 years while on treatment, with loss of CD123 expression. At relapse, the neoplasm was comprehensively immunophenotyped by flow cytometry (performed on both peripheral blood and bone marrow specimen) and by immunohistochemical evaluation of the bone marrow clot section. The neoplasm at relapse was diagnostic of BPDCN with a lack of CD123 expression. This case highlights a potential limitation of current and upcoming tagraxofusp-based multidrug therapies, at least in a subset of refractory BPDCN. We believe our report will serve as a sentinel to incite future investigations involving alternate resistance mechanisms in BDPCN.

Highlights

Targeted therapy has found a new success story through the growing utility of tagraxofusp, a CD123-directed antineoplastic drug
Immunohistochemistry (IHC) on the bone marrow clot section (Fig. 2C–E) showed expression of TCL1 and confirmed the expression of CD56 and absence of CD123, CD303 (BDCA-2), cytokeratin, CD138, and CD68, MPO, CD3, and PAX-5 with adequately working controls. Karyotype at this time showed 45,XY,add(12)(p10),−20,+mar[1 2]/46,XY[8]. These immunomorphological findings confirmed a relapse of Blastic plasmacytoid dendritic cell neoplasm (BPDCN) without expression of CD123
We report a relapse of BPDCN while on treatment with single-agent tagraxofusp (12uL/kg), with no identifiable expression of CD123 as evaluated by two different methods (IHC and flow cytometry) and two different antibody clones

Summary

Introduction

Targeted therapy has found a new success story through the growing utility of tagraxofusp, a CD123-directed antineoplastic drug. Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive neoplasm derived from the precursor plasmacytoid dendritic cells characterized by the expression of CD303, CD123, CD56 CD4, and TCL1, [3,4,5] This ubiquitous expression of CD123 makes BPDCN a prime target for treatment with tagraxofusp, as described in a pilot study by Frankel et al [6]. The FDA approved tagraxofusp for the management of BPDCN in December 2018 The utility of this promising new drug extends potentially to other neoplasms strongly expressing CD123, including acute myeloid leukemia (AML) [8], hairy cell leukemia [9], and B-lymphoblastic leukemia [10]. The effectiveness of this drug has been tested in tyrosine kinase-resistant CML [11]

Methods

Discussion

Conclusion