Abstract Background Blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive hematologic neoplasm that expresses CD123, is often observed in the bone marrow (BM), as well as skin, blood, and viscera. Tagraxofusp, a first‐in‐class CD123‐targeted therapy, is the only drug approved to treat BPDCN. Methods The authors conducted a post hoc analysis of the pivotal phase 2 trial to evaluate hematopoietic and BM effects of first‐line tagraxofusp treatment (12 µg/kg per day on days 1–5 of a 21‐day cycle) over time. This trial was registered at www.clinicaltrials.gov (ClinicalTrials.gov identifier NCT02113982). Results Of 66 treatment‐naive patients in this analysis, 32 had baseline BM disease, and 34 had no BM disease. Over the course of tagraxofusp monotherapy treatment, neutrophil levels restored to normal, mirrored by a decreasing incidence of neutropenia and granulocyte‐colony–stimulating factor administration from baseline with each cycle of treatment. Similarly, platelet counts recovered during treatment, whereas thrombocytopenia incidence and requirement for platelet transfusions decreased from baseline. Hemoglobin levels improved during tagraxofusp treatment, correlating with a decrease in the incidence of anemia and the number of transfusions from baseline. By cycle 2, all patients had peripheral blast clearance regardless of BM status. Patients with BM disease who did or did not achieve a complete response/clinical complete response during treatment experienced similar restoration of hematopoiesis, including peripheral blast eradication. Conclusions These findings demonstrate the on‐target effect and unique BM‐sparing profile of tagraxofusp, which are paramount when treating myelosuppressive, CD123‐positive hematologic diseases. The results support single‐agent tagraxofusp as standard‐of‐care, nonmyelosuppressive first‐line treatment for BPDCN and as a potential combination partner for other CD123‐positive hematologic malignancies.
Konopleva et al. (Thu,) studied this question.