Moxetumomab pasudotox-tdfk (Lumoxiti), is a CD22-directed cytotoxin, to treat hairy cell leukemia, consisting of the Fv portion of the anti-CD22 monoclonal antibody which is coupled to a large fragment of the Pseudomonas exotoxin A.
Binds to CD22 proteins on the surface of the leukemia cells and delivers a toxin that triggers apoptic cell death.
The therapy is directed to Cells overexpressing sialic acid-binding transmembrane proteins CD22.
Once the immunotoxin finds the CD22 receptor, the complex is then internalized via endocytosis and after internalization the toxin is released from the complex, ultimately leading to initiation of the apoptic cascade.
Approved to treat adults with relapsed or refractory HCL who have received at least two prior systemic therapies, including treatment with a purine nucleoside analog.
It poses risks of capillary leak syndrome and hemolytic uremic syndrome, risk of decreased renal function, infusion-related reactions, and electrolyte abnormalities.
Approval based on results from a phase 3 trial.
Moxetumomab pasudotox-tdfk (Lumoxti) a CD22-directed cytotoxin, is now approved for the treatment of adult patients with relapsed or refractory HCL who have received at least 2 prior systemic therapies, including treatment with a purine nucleoside analog.
This approval is based on a single-arm, open-label clinical trial of 80 patients that measured durable complete response (CR), defined as maintenance of hematologic remission for more than 180 days after achievement of CR.
Results of the trial showed that 30% of patients achieved durable CR; the overall response rate was 75%.
Common adverse events associated with moxetumomab pasudotox-tdfk include infusion-related reactions, swelling caused by excess fluid in body tissue, nausea, fatigue, headache, fever, constipation, anemia, and diarrhea.
Patients with relapsed or refractory HCL who had received at least two prior lines of therapy had a median of 16.7 months of follow-up, the objective response rate was 75%, the complete response (CR) rate was 41%, and the durable CR rate was 30%.
82% patients with a CR achieved minimal residual disease negativity.
The median duration of response was not reached, nor was the median progression-free survival.
The most common treatment-related adverse events: nausea, peripheral edema, headache, and pyrexia, infections and neutropenia.
Reasons for discontinuation included capillary leak syndrome, hemolytic uremic syndrome, and increased blood creatinine.