Combination of Tagraxofusp and Azacitidine Is an Effective Option for Relapsed Blastic Plasmacytoid Dendritic Cell Neoplasm After Allogeneic Hematopoietic Stem-Cell Transplantation

Wang, Song‐Yau; Thomassen, Katrin; Kurch, Lars; Opitz, Sabine; Franke, Georg-Nikolaus; Bach, Enrica; Platzbecker, Uwe; Käyser, Sabine

doi:10.1016/j.clml.2021.02.008

Cited by 10 publications

(6 citation statements)

References 17 publications

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“…Secondly, tagraxofusp resistance in both AML and BPDCN was associated with increased overall apoptotic priming and showed increased dependence on BCL-2 and or BCL-XL [15]. Such results have led to multiple trials evaluating combinations of tagraxofusp, azacitidine, and venetoclax (BCL-2 inhibitor) in BPDCN {NCT03113643, NCT03485547, and NCT04216524} Along similar lines, success stories of combination tagraxofusp and azacitidine in the management of relapsed BPDCN [22] highlight bright scope for specific multidrug management in BPDCN.…”

Section: Discussionmentioning

confidence: 97%

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

Gulati

Abu-Salah

Salous³

et al. 2021

J Hematopathol

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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.

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Section: Discussionmentioning

confidence: 97%

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

Gulati

Abu-Salah

Salous³

et al. 2021

J Hematopathol

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“…Given the reduction in white blood cell count and hemoglobin following Ven/Aza therapy in our patient, he will need regular monitoring with weekly cycles of chemotherapy. Trials investigating the effects of venetoclax either as a single agent (NCT03485547) or in combination with tagraxofusp (NCT03113643) are ongoing [ 15 - 16 ].…”

Section: Discussionmentioning

confidence: 99%

Venetoclax and Azacitidine in the Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm Refractory to Conventional Therapy

Azad¹,

Zhang²,

Miranda³

et al. 2022

Cureus

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Blastic plasmacytoid dendritic cell neoplasm is a rare and aggressive hematological malignancy associated with poor prognosis and limited treatment options. No guideline-directed therapy existed until the approval of tagraxofusp in 2018 by the Food and Drug Administration. Multiple clinical trials are undergoing as treatment options continue to evolve. We report a case refractory to tagraxofusp and pivekimab sunirine with subsequent remission achieved on venetoclax and azacitidine therapy.

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Section: Togami Et Al Elegantly Describe the Persistent Expression Of Cd123 During And After Treatment In Bpdcnmentioning

confidence: 99%

Tagraxofusp Refractory Blastic Plasmacytoid Dendritic Cell Neoplasm With Loss of CD123 Expression: Case and Review of Literature

Gulati

Abu-Salah

Salous

et al. 2021

Preprint

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Background: 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 showed 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. Case presentation: Herein we report a case of an elderly male with BPDCN that initially achieved complete remission on primary treatment with tagraxofusp. However, BPDCN relapsed after 1.5 years while on treatment with loss of CD123 expression. Conclusions: This case highlights a potential limitation of current and upcoming tagraxofusp based 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.

show abstract

Combination of Tagraxofusp and Azacitidine Is an Effective Option for Relapsed Blastic Plasmacytoid Dendritic Cell Neoplasm After Allogeneic Hematopoietic Stem-Cell Transplantation

Cited by 10 publications

References 17 publications

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

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

Venetoclax and Azacitidine in the Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm Refractory to Conventional Therapy

Tagraxofusp Refractory Blastic Plasmacytoid Dendritic Cell Neoplasm With Loss of CD123 Expression: Case and Review of Literature

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