Abstract Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an extremely rare hematologic malignancy with an aggressive course and poor prognosis. Treatment remains challenging particularly in patients who are ineligible for stem cell transplantation due to resistance to conventional chemotherapy. The introduction of tagraxofusp, a CD123-directed cytotoxin, has significantly expanded therapeutic options and improved outcomes for patients with BPDCN. However, its use can be accompanied by notable adverse events, especially capillary leak syndrome, underscoring the need for careful patient selection and monitoring. Up to date, no data is available regarding the safety of tagraxofusp in patients with chronic kidney failure and cardiovascular co-morbidities. We present the case of a 79-year-old male who developed a solitary, rapidly progressing skin lesion on his lower back. The lesion represented the first manifestation of BPDCN with bone marrow infiltration and concomitant myelodysplastic syndrome (MDS). Molecular analysis identified mutations in CBL, TET2, ZRSR2 and KRAS. Non-eligible for stem cell transplantation, the patient was admitted to treatment with tagraxofusp in a dose-reduced protocol due to concomitant chronic kidney disease (CKD). After three doses of the first cycle, treatment needed to be stopped due to acute-on-chronic renal failure. After treatment disruption, kidney failure was completely restituted to pre-treatment levels. Notably, skin and bone marrow biopsies demonstrated a dermatologic complete response and partial remission of bone marrow infiltration. A watch and wait concept was followed, and prolonged therapy response was obtained for 8 months before relapse. To our knowledge, this is the first reported case demonstrating the use of tagraxofusp in a patient with BPDCN and advanced chronic kidney disease, showing that even a minimum of tolerated treatment dose can induce a sustained response. Despite the risk of adverse events, tagraxofusp should be considered a viable treatment option for elderly patients with poor performance status and significant comorbidities who are ineligible for intensive chemotherapy or stem cell transplantation, as even limited exposure may achieve meaningful clinical responses.
Brummer et al. (Thu,) studied this question.