The newly approved immunotoxin, moxetumomab pasudotox, fulfills the criteria for magic bullets, a term first coined by Nobel Laureate Paul Ehrlich 100 years ago.1 It contains a portion of monoclonal antibody against CD 22 conjugated with a modified pseudomonas exotoxin (PE38) and thus targets and introduces PE38 into malignant B cells without damaging other cells.2 However, this well-designed drug seems to attack endothelial cells.2
A 74-year-old Caucasian female with a complicated history of malignancies including variant subtype of hairy cell leukemia, squamous cell lung cancer, and ductal carcinoma in the breast. Both lung and breast cancers were in remission after surgeries and chemotherapy or radiation. Her hairy cell leukemia variant has been treated with purine analogs, rituximab, and splenectomy, but she relapsed and failed standard therapy. She was started on moxetumomab pasudomtox (0.04 mg/kg intravenously every other day) and developed severe nausea, vomiting, and weakness 2 days following the third dose. On admission, her blood pressure was 188/100 mm Hg, pulse rate 87/min, and O2 saturation 79% on room air. She had wheezing and crackles bilaterally, and edema in lower extremities. Her platelet counts, hemoglobin, and serum creatinine levels deteriorated rapidly (Figure). Her urinalysis showed 3+ proteinuria, 24 red and 22 white blood cells, and some granular casts. She had schistocytes, lactate dehydrogenase 1,790 u/L, and haptoglobin undetectable, consistent with microangiopathic hemolysis. Her albumin level was 2.9 g/dL, international normalized ratio 1.0, and chest X-ray revealing bilateral infiltrates. Other pertinent results includes a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 level 93%, Complement 3 and 4 level 114 and 13 mg/dL, respectively, and negative blood and urine cultures.
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-Yeong-Hau H. Lien, MD, PhDa,b, Michael Boxer, MD
This article originally appeared in the December 2019 issue of The American Journal of Medicine.
