December 30, 2018 – Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive and rare disease of the bone marrow and blood that can affect multiple organs, including the lymph nodes and the skin and often presents as or evolves into acute leukemia. The disease is more common in men than women and in patients 60 years and older. Until now, the standard of care for BPDCN has been intensive chemotherapy followed by bone marrow transplantation. However, many patients with BPDCN were unable to tolerate this intensive therapy, and therefore an urgent need for alternative treatment options for this rare condition existed for quite some time already.
Capillary leak syndrome; life-threading and potentially fatal.
This may change now. On December 21, 2018, the American Food and Drug Administration (FDA) just approved Tagraxofusp-erzs (Elzonris) for the targeted treatment of BPDCN in adults and in pediatric patients, two years of age and older. Tagraxofusp-erzs is a interleukin-3 receptor (CD123) directed cytotoxin composed of recombinant human interleukin-3 (IL-3) and truncated diphtheria toxin (DT) fusion protein that inhibits protein synthesis and causes cell death in CD123- expressing cells.
The efficacy of Tagraxofusp-erzs (Elzonris) was studied in two cohorts of patients in a single-arm clinical trial. The first trial cohort enrolled 13 patients with untreated BPDCN, and seven patients (54%) achieved complete remission (CR) or CR with a skin abnormality not indicative of active disease (CRc). The second cohort included 15 patients with relapsed or refractory BPDCN. One patient achieved CR and one patient achieved CRc.
Common side effects reported by patients in clinical trials were capillary leak syndrome (fluid and proteins leaking out of tiny blood vessels into surrounding tissues), nausea, fatigue, swelling of legs and hands (peripheral edema), fever (pyrexia), chills and weight increase. Most common laboratory abnormalities were decreases in lymphocytes, albumin, platelets, hemoglobin and calcium, and increases in glucose and liver enzymes (ALT and AST). Health care providers are advised to monitor liver enzyme levels and for signs of intolerance to the infusion. Women who are pregnant or breastfeeding should not take Tagraxofusp-erzs (Elzonris) because it may cause harm to a developing fetus or newborn baby. The labeling for Tagraxofusp-erzs (Elzonris) contains a Black boxed Warning to alert health care professionals and patients about the increased risk of capillary leak syndrome which may be life-threatening or fatal to patients in treatment.
In terms of patient safety, both physicians and patients need to exert extreme caution. Tagraxofusp-erzs (Elzonris) was approved based on clinical data obtained from a very minimal number of patients (28 patients from two cohorts only) and yet, the impressive collection of adverse effects, as indicate above, have been noted. And, most troublesome, one of the effects, namely capillary leak syndrome, can truly be life-threatening and fatal for affected patients.
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About the Author
Ph.D.; Professor in Pharmacology and Toxicology.
Senior expert in theragenomic and personalized medicine and individualized drug safety.
Senior expert in pharmaco- and toxicogenetics.
Senior expert in human safety of drugs, chemicals, environmental pollutants, and dietary ingredients.
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