Dr. Daver on the Use of ADCs in BPDCN

Naval Daver, MD, associate professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the use of antibody-drug conjugates (ADC) in the treatment of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN).

The only therapy currently approved by the FDA for the treatment of BPDCN is tagraxofusp-erzs (SL-401; Elzonris), a first-in-class, CD123-targeted ADC. Findings from a phase 1/2 trial (NCT02113982), which supported the FDA approval of tagraxofusp in December 2018, showed that 29 patients treated in the confirmatory phase of the trial experienced a complete response (CR), CR with a skin abnormality not indicative of active disease (CRc), and CR with incomplete hematologic recovery (CRi) rate of 72%.

Despite its approval, Daver notes that patients with BPDCN who are treated with tagraxofusp must still be monitored carefully for adverse effects (AEs). AEs associated with tagraxofusp include capillary leak syndrome and significant edema, which both can have sudden onset, Daver explains. However, with careful monitoring and appropriate dose interruptions, tagraxofusp can be a tolerable drug, Daver continues.

Although venetoclax (Venclexta) has shown promise in BPDCN, and the standard-of-care approach of intensive chemotherapy remains a treatment option for patients with BPDCN, another ADC is currently under investigation for this patient population.

Pivekimab sunirine (IMGN632) is another CD123-targeted ADC; however, this agent utilizes an indolinobenzodiazepine cytotoxic alkylating payload. Thus far, investigators have observed limited edema and capillary leak syndrome with this ADC, making it a potentially safer option compared with tagraxofusp, Daver says. Data from a first-in-human phase 1/2b trial (NCT03386513) showed that 2 of 9 patients with BPDCN treated with pivekimab sunirine achieved a CR/CRi, and 1 patient had a partial response, leading to a breakthrough therapy designation from the FDA in October 2020.

Pivekimab sunirine represents another potential treatment option for patients with BPDCN, and it is also being studied in combination regimens for patients with acute myeloid leukemia, Daver concludes.