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Tagraxofusp treatment for BPDCN continues to evolve


A recent paper details the different ways scientists are investigating tagraxofusp to treat blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare hematologic malignancy that often presents with skin manifestations.

Nearly two years after the FDA approved tagraxofusp (Elzonris, Stemline) as the first targeted therapy indicated for BPDCN, scientists are starting to look at different ways to treat BPDCN with tagraxofusp to improve outcomes, according to a paper published August 25 in Blood Advances.

Even defining this rare hematologic malignancy, which often presents with skin manifestations, has changed notably in recent years. The World Health Organization (WHO) gave BPDCN its name and categorized it under acute myeloid leukemia and related neoplasms in 2008. But in 2016, WHO made a separate category for BPDCN under myeloid neoplasms.

RELATED: Tagraxofusp comparable to other chemo regimens as first-line therapy

BPDCN accounts for less than 1% of all hematologic malignancies and less than 1% of cutaneous lymphoma/lymphoma-like entities, according to U.S. Surveillance, Epidemiology, and End Result (SEER) data.

A male-predominant cancer, BPDCN has a history of dismal outcomes. Researchers reporting on survival in BPDCN patients receiving intensive chemotherapy regimens prior to the targeted era of treatment found patients’ median overall survival was less than two years.

“With its varied clinical presentation and challenging management features, the treatment approach to BPDCN has historically centered around multiagent chemotherapy regimens repurposed from acute leukemias and lymphomas, with notably suboptimal rates, including high early death rates and complete remissions (CRs) of [about] 40% to 60% in most larger series,” the authors wrote.

Doctors have used autologous and allogeneic stem cell transplants for some BPDCN patients after chemotherapy treatment to improve survival. But many older patients with BPDCN are not stem cell transplant candidates.

BPDCN research and ultimately treatment took an important step forward when scientists confirmed BPDCN is a CD123-high–expressing tumor. Published studies revealed a consistent and reproducible immunophenotypic BPDCN profile.

“The triad of positivity for CD123, CD4, and CD56 (or, as we have put forward as a helpful memory device, ‘Think 123456’) has yielded a high level of sensitivity for this elusive diagnosis,” the authors wrote. “Furthermore, additional markers, including TCL-1, CD303, and TCF4, have all added specificity in securing a diagnosis of BPDCN, particularly in the context of differentiating from mimicking diseases such as [acute myeloid leukemia] with leukemia cutis.”

RELATED: What dermatologists should know about blastic plasmacytoid dendritic cell neoplasm

Researchers also began studies looking at the potential BPDCN treatment tagraxofusp, a targeted therapy directed to CD123 (IL-3R).A pilot study and subsequent larger phase 1/2 multicenter clinical trial looking at treating BPDCN with tagraxofusp found 90% overall response rate with median overall survival at 24 months at 52% in frontline and 67% overall response rate with median overall survival reported at 8.5 months in the relapsed/refractory setting.

“Remarkably, 45% of these frontline-treated patients were able to be bridged successfully to [stem cell transplant],” according to the authors.

Tagraxofusp, however, does have novel toxicities and carries a black box warning for capillary leak syndrome. Researchers evaluated 94 patients with hematologic malignancies for safety in tagraxofusp clinical trials and found capillary leak syndrome occurred in 55%, or 52 of 94 patients, at all grades. The authors recommend an individualized approach to manage capillary leak syndrome, using a three-pronged approach, including recognition and education, close follow-up, and aggressive team-based early intervention.

Future therapy directions in BPDCN and acute myeloid leukemia fields including using tagraxofusp as a single agent or in combination treatments. Among the regimens being studied, a novel triplet treatment combining tagraxofusp with venetoclax and HCVAD chemotherapy. Researchers have also launched a single-center post-stem cell transplant maintenance study for patients with BPDCN treated with tagraxofusp, according to the paper.

“Now, 1.5 years after [tagraxofusp] as a monotherapy agent has been approved, it will be of high interest to continue investigation of this CD123-directed therapy in rational combinations with other targeted agents, hypomethylating agents, and cytotoxic chemotherapy in patients with BPDCN and other hematologic malignancies that overexpress CD123,” the authors wrote.

MORE ON BPDCN: FDA-approved treatment puts rare cancer with skin manifestations on the map

Disclosures: MD Anderson Cancer Center and the SagerStrong Foundation funded the work. The authors have industry ties including Stemline.

Pemmaraju N, Konopleva M. Approval of tagraxofusp-erzs for blastic plasmacytoid dendritic cell neoplasm. Blood Adv. 2020;4(16):4020-4027. doi:10.1182/bloodadvances.2019000173

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