Venetoclax to treat relapsed blastic plasmacytoid dendritic cell neoplasm: A case-report and review of literature

Beziat, Guillaume; Ysebaert, Loïc; Gaudin, C.; Steinmeyer, Zara; Balardy, L.

doi:10.1016/j.leukres.2019.106199

Cited by 9 publications

(8 citation statements)

References 7 publications

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“…BPDCN cells collected from PDX or directly from patient skin and bone marrow showed higher BCL-2 dependency compared with randomly selected AML cases (86). In vivo experiments confirmed these findings and, to date, several reports have been published about relapsed BPDCN patients successfully treated with single-agent venetoclax (87,88). Such therapeutic approach is currently being investigated in a phase I clinical trial (NCT03485547).…”

Section: Blastic Plasmacytoid Dendritic Cell Neoplasmsupporting

confidence: 55%

“… 86 In vivo experiments confirmed these findings and, to date, several reports have been published about patients with relapsed blastic plasmacytoid dendritic cell neoplasm successfully treated with single-agent venetoclax. 87 , 88 Such a therapeutic approach is currently being investigated in a phase I clinical trial (NCT03485547).…”

Section: The Anti-apoptotic Map Of Hematologic Malignanciesmentioning

confidence: 99%

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The mitochondrial anti-apoptotic dependencies of hematologic malignancies: from disease biology to advances in precision medicine

2022

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Mitochondria are critical organelles in the regulation of intrinsic apoptosis. As a general feature of blood cancers, different anti-apoptotic members of the BCL-2 protein family localize at the outer mitochondrial membrane to sequester variable amounts of pro-apoptotic activators, and hence protect cancer cells from death induction. However, the impact of distinct anti-apoptotic members on apoptosis prevention, a concept termed anti-apoptotic dependence, remarkably differs across disease entities. Over the last two decades, several genetic and functional methodologies have been established to uncover the anti-apoptotic dependencies of the majority of blood cancers, inspiring the development of a new class of small molecules called BH3 mimetics. In this review, we highlight the rationale of targeting mitochondrial apoptosis in hematology, and provide a comprehensive map of the antiapoptotic dependencies that are currently guiding novel therapeutic strategies. Cell-extrinsic and intrinsic mechanisms conferring resistance to BH3 mimetics are also examined, with insights on potential strategies to overcome them. We finally discuss how the field of mitochondrial apoptosis might be complemented with other dimensions of precision medicine for more successfully treating ‘highly complex’ hematological malignancies.

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Section: Blastic Plasmacytoid Dendritic Cell Neoplasmsupporting

confidence: 55%

Section: The Anti-apoptotic Map Of Hematologic Malignanciesmentioning

confidence: 99%

The mitochondrial anti-apoptotic dependencies of hematologic malignancies: from disease biology to advances in precision medicine

2022

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“…At the time of writing this paper, more results of venetoclax use are available. In another case report by Beziat et al , the patient did not exhibit a very good response, as some cutaneous lesions remained stable while others responded [ 11 ]. Then, two other papers in combination therapy with hypometilating agents report pretty good results, with rapid and durable responses [ 12 , 13 ].…”

Section: Discussionmentioning

confidence: 99%

Venetoclax in relapsed/refractory blastic plasmacytoid dendritic cell neoplasm with central nervous system involvement: a case report and review of the literature

et al. 2021

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Background We describe a patient with blastic plasmacytoid dendritic cell neoplasm with central nervous system involvement and the outcome of venetoclax use in this setting. Case presentation A 54-year-old Caucasian male was referred to the Haematology Unit with an enlarged inguinal lymph node which was diagnostic of a blastic plasmacytoid dendritic cell neoplasm. The staging revealed disseminated disease (skin, visceral, lymph nodes, and bone marrow). He received chemotherapy with an acute myeloid leukaemia-like regime. Afterwards, he underwent allogeneic haematopoietic stem cell transplantation, though it was not successful, showing a relapse 14 months later with hepatic and central nervous system dissemination. Intrathecal chemotherapy was administered, and venetoclax (anti-bcl2 agent) was started in an off-label indication based on most recent literature. The disease halted its course for 3 months. In the end, the patient’s disease progressed and so he succumbed due to infectious complications. Conclusions Venetoclax monotherapy seems not enough to control the disease progression under CNS involvement and other treatments should be investigated.

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“…31 It appears that venetoclax monotherapy achieves clinical remission predominantly in cutaneouslimited disease; however, there are case reports of nearcomplete resolution of lymphadenopathy on positron emission tomography-computed tomography and 50% reduction in BPDCN blast count. 39,40 Venetoclax is undergoing clinical trials to be used in relapsed/refractory BPDCN (NCT03485547). Evidence in support of this treatment approach is described in 1 case report in which a patient achieved major cutaneous response after 5 cycles of treatment with venetoclax, tagraxofusp, and azacitidine.…”

Section: Bcl2 Inhibitorsmentioning

confidence: 99%

Blastic plasmacytoid dendritic cell neoplasm (BPDCN): A promising future in the era of targeted therapeutics

Adimora

Wilson

Pemmaraju

2022

Cancer

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Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy arising from precursor dendritic cells. BPDCN cells characteristically express several markers on their cell surfaces including CD123, CD4, and CD56. Because of its rarity and challenging clinical presentation, there was no standard of care in managing BPDCN for decades and its prognosis overall was poor. However, as understanding of this rare neoplasm has increased, so have treatment options. The conventional cytotoxic chemotherapy regimens once used in the treatment of BPDCN were modest in their impact on disease relapse until paired with hematopoietic stem cell transplant. Although recent data suggest that there still remains a role for chemotherapeutic agents, targeted modalities have expanded the overall BPDCN treatment landscape. The CD123-targeted agent, tagraxofusp, was the first Food and Drug Administration-approved monotherapy in the treatment of BPDCN. Since its inception, several CD123-targeted and other cell-surface agents have been investigated, with many agents still in the preclinical stages. Although relapsed/refractory disease and central nervous system disease both remain formidable areas of research, there are several promising therapeutic approaches that could have a significant impact on the trajectory of treatment. This review will provide detailed insight on the novel drugs currently in use and those being explored in the management of BPDCN.

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Venetoclax to treat relapsed blastic plasmacytoid dendritic cell neoplasm: A case-report and review of literature

Cited by 9 publications

References 7 publications

The mitochondrial anti-apoptotic dependencies of hematologic malignancies: from disease biology to advances in precision medicine

The mitochondrial anti-apoptotic dependencies of hematologic malignancies: from disease biology to advances in precision medicine

Venetoclax in relapsed/refractory blastic plasmacytoid dendritic cell neoplasm with central nervous system involvement: a case report and review of the literature

Blastic plasmacytoid dendritic cell neoplasm (BPDCN): A promising future in the era of targeted therapeutics

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