The FDA approved moxetumomab pasudotox-tdfk (Lumoxiti, AstraZeneca/MedImmune) injection for intravenous use to treat adults with relapsed or refractory hairy cell leukemia (HCL) who have received at least two prior systemic therapies, including treatment with a purine nucleoside analog. 

Moxetumomab pasudotox-tdfk is a CD22-directed cytotoxin and is the first of this type of treatment for patients with HCL.

“While many patients with hairy cell leukemia experience a remission with current treatments, 30% to 40% will relapse five to 10 years after their first treatment,” said Robert J. Kreitman, MD, a senior investigator and the head of the Clinical Immunotherapy Section in the National Cancer Institute's Center for Cancer Research. “With subsequent treatments, durations of response diminish and toxicities accumulate, and few approved treatment options exist. Moxetumomab pasudotox represents a promising non-chemotherapeutic agent for HCL, addressing an unmet medical need for physicians and their patients,” said Dr. Kreitnman, who was also the principal investigator of the phase 3 clinical trial, that the FDA considered for the approval.

The efficacy of moxetumomab pasudotox-tdfk was studied in a single-arm, open-label clinical trial of 80 patients with histologically confirmed HCL or HCL variant requiring treatment based on the presence of cytopenias or splenomegaly, and who had received prior treatment with at least two systemic therapies, including one purine nucleoside analog. Eligible patients had a serum creatinine of 1.5 mg/dL or less or a creatinine clearance of 60 mL per minute or higher, as estimated by the Cockcroft-Gault equation. Of the enrolled patients, 77 had classic HCL and three had HCL variant. Patients received a 0.04 mg/kg IV infusion of moxetumomab pasudotox-tdfk over 30 minutes on days 1, 3 and 5 of each 28-day cycle, for a maximum of six cycles or until documentation of complete response (CR), disease progression or unacceptable toxicity. 

 
Efficacy in HCL was evaluated by a blinded independent review committee (IRC)-assessed rate of durable CR confirmed by maintenance of hematologic remission (hemoglobin ≥11 g/dL, neutrophils ≥1,500/mm3, and platelets ≥100,000/mm3 without transfusions or growth factor for at least four weeks) more than 180 days after IRC-assessed CR. The IRC-assessed durable CR rate was 30% (24/80 patients; 95% CI, 20-41). The IRC-assessed CR rate was 41% (33/80 patients; 95% CI, 30-53).

The most common nonlaboratory adverse reactions of any grade were infusion-related reactions, edema, nausea, fatigue, headache, pyrexia, constipation, anemia and diarrhea. The most common grade 3 or 4 adverse reactions (reported in ≥5% of patients) were hypertension, febrile neutropenia and hemolytic uremic syndrome (HUS). Adverse reactions resulting in permanent discontinuation of moxetumomab pasudotox-tdfk occurred in 15% (12/80) of patients. The most common adverse reaction leading to discontinuation was HUS. The most common adverse reaction resulting in dose delays, omissions or interruptions was pyrexia.

The prescribing information for moxetumomab pasudotox-tdfk includes a boxed warning to advise health care professionals and patients about the risk for developing capillary leak syndrome, a condition in which fluid and proteins leak out of tiny blood vessels into surrounding tissues. The boxed warning also notes the risk for HUS, a condition caused by the abnormal destruction of red blood cells. Patients should be made aware of the importance of maintaining adequate fluid intake, and blood chemistry values should be monitored frequently.

Other serious warnings include decreased renal function, infusion-related reactions and electrolyte abnormalities. Moxetumomab pasudotox-tdfk is not recommended in patients with severe renal impairment (CrCl ≤ 29 mL/min) or in women who are breastfeeding.

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—Clinical Oncology News Staff

—Based on FDA and company press materials