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Venetoclax monotherapy for cutaneous BPDCN

Publication
Article
Dermatology TimesDermatology Times, December 2020 (Vol. 41, No. 12)
Volume 41
Issue 12

B-cell lymphoma-2 inhibitor venetoclax has shown in clinical studies to improve symptoms with minimal toxicity in patients with cutaneous blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive hematologic cancer that can be rapidly fatal without treatment.

The B-cell lymphoma- (BCL-) 2 inhibitor venetoclax may have a role in rapidly treating predominately cutaneous blastic plasmacytoid dendritic cell neoplasm (BPDCN) with minimal systemic toxicity, according to a letter to the editor published September 23 in Annals of Hematology.

An aggressive hematologic cancer that can be rapidly fatal without treatment, BPDCN most commonly presents with cutaneous lesions. Many BPDCN patients also have lymphadenopathy, splenomegaly and cytopenia.

Clinicians might treat BPDCN with multi-agent chemotherapy, and while some patients experience remission on these regimens, remission is likely transient. Many believe BPDCN is incurable without allogeneic hematopoietic cell transplant.

The U.S. Food and Drug Administration (FDA) recently approved the CD123-directed cytotoxin tagraxofusp for treatment of BPDCN, based on trials that yielded a 72% complete response and 90% overall response in newly diagnosed patients. BPDCN arises from precursors of plasmacytoid dendritic cells, with immunohistochemical staining generally positive for CD4, CD56, CD123 and TCL-1, the authors wrote.

“However, tagraxofusp is associated with significant toxicities, including a potentially fatal capillary leak syndrome,” they wrote.

Venetoclax could be another treatment option, as recent in vitro studies have shown BPDCN depends on the BCL-2 protein to prevent apoptosis. There is in vivo research on BPDCN suggesting animals treated with oral venetoclax had improved survival. And authors of recent reports describe using venetoclax alone or in combination to treat newly diagnosed and relapsed/refractory BPDCN, according to the paper.

Authors of a research brief published February 2017 in Cancer Discovery used primary tumor cell functional profiling to predict BCL2 antagonist sensitivity as a common feature of BPDCN. They found in vivo clinical activity of venetoclax in patient-derived xenografts and in two patients with relapsed chemotherapy-refractory disease.

The authors of the Annals of Hematology paper add to the literature with a case of an 88-year-old man, presenting to his dermatologist with a 10-month history of what they described as progressive, non-ulcerated, violaceous cutaneous plaques. The non-pruritic and painless plaques appeared at first on his right lower leg, but later involved his left leg, chest, scalp and back. Topical steroids did not help, according to the patient.

Punch biopsies of the plaque showed dense, nodular and sheet-like, monomorphous infiltrate extending into the subcutis. And immunohistochemical studies revealed the cells were positive for CD4, CD56, CD123, TCL-1 and BCL-2, which is consistent with BPDCN.

“On our initial exam, the patient had indurated, well demarcated, and violaceous plaques over the bilateral legs, chest, and back, with overlying scale on the plaques of the lower legs. The right lower extremity had tense edema. He was otherwise asymptomatic and strongly preferred to avoid hospitalization and potential treatment-related toxicities,” they wrote. “After discussing all therapeutic options, we proceeded with venetoclax 400 mg daily.”

The patient’s plaques markedly improved after four weeks. His right lower extremity plaque had minimal residual macular hyperpigmentation and no associated edema after eight weeks on venetoclax. The other lesions resolved completely, they wrote.

The patient experienced transient neutropenia at week 8 of treatment, but that was the only adverse effect from the drug.

“For patients deemed unfit for tagraxofusp, BCL-2 inhibition is a promising alternative and is currently being investigated in a phase I trial (NCT03485547),” they wrote.

Disclosure: Two of the study’s authors have research, consulting or advisory roles with Glycomimetics, Gilead, Jazz Pharmaceuticals, Abbvie, Agios, BMS, Genentech and Pfizer.

Reference:

Schwede M, Tan IT, Atibalentja DF, Dickman MM, Rieger KE, Mannis GN. Venetoclax monotherapy for cutaneous blastic plasmacytoid dendritic cell neoplasm. Ann Hematol. 2020 Sep 23. doi: 10.1007/s00277-020-04276-z. Epub ahead of print. PMID: 32968828.

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