New Treatment for Hairy Cell Leukemia Granted FDA Approval
Officials with the FDA have approved AstraZeneca’s moxetumomab pasudotox-tdfk (Lumoxiti) injection for intravenous use for the treatment of adult patients with relapsed or refractory hairy cell leukemia who have received at least 2 prior systemic therapies.
Officials with the FDA have approved AstraZeneca’s moxetumomab pasudotox-tdfk (Lumoxiti) injection for intravenous use for the treatment of adult patients with relapsed or refractory hairy cell leukemia (HCL) who have received at least 2 prior systemic therapies, including treatment with a purine nucleoside analog.1,2 Lumoxiti is a CD22-directed cytotoxin and is the first of this type of treatment for patients with HCL.1
“Lumoxiti fills an unmet need for patients with hairy cell leukemia whose disease has progressed after trying other FDA-approved therapies,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, in a prepared statement.1 “This therapy is the result of important research conducted by the National Cancer Institute that led to the development and clinical trials of this new type of treatment for patients with this rare blood cancer.”
According to AstraZeneca’s Dave Fredrickson, Executive Vice-President, Global Head Oncology Business Unit, Lumoxiti represents the first FDA-approved medicine for HCL in more than 20 years.2
The FDA granted approval for this drug under Fast Track and Priority Review designations. Lumoxiti also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.1
The approval is based on data from the Phase III single-arm, open-label ‘1053’ trial of Lumoxiti monotherapy in 80 patients who have received at least 2 prior therapies, including a purine nucleoside analog. The primary endpoint of the trial was durable complete response (CR), defined as maintenance of hematologic remission for more than 180 days after achievement of CR. Thirty percent of patients in the trial achieved durable CR, and the overall response rate was 75%.1.2
The median time to haematologic remission was 1.1 months (range: 0.2 to 13).2 At data cut-off, the median duration of complete response was not yet reached after a median 16.7 months of follow-up.2
Common adverse effects of moxetumomab pasudotox-tdfk include infusion-related reactions, swelling caused by excess fluid in body tissue, nausea, fatigue, headache, fever, constipation, anemia and diarrhea.1,2
Lumoxiti is not recommended in patients with severe renal impairment (CrCl ≤ 29 mL/min). The Phase III trial results demonstrated 75% (95% confidence interval [CI]: 64, 84) of patients receiving Lumoxiti achieved an overall response; 30% (95% CI: 20, 41) had a durable complete response.
“While many patients with hairy cell leukemia experience a remission with current treatments, 30% to 40% will relapse 5 to 10 years after their first treatment,” said Robert J. Kreitman, MD, Senior Investigator, Head of Clinical Immunotherapy Section, Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, and Principal Investigator of the Phase III clinical trial, said, in a prepared statement.2 “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.”
The recommended dose of Lumoxiti is 0.04 mg/kg administered as an intravenous infusion over 30 minutes on days 1, 3, and 5 of each 28-day cycle up to 6 cycles, disease progression, or unacceptable toxicity.2
The prescribing information for Lumoxiti includes a Boxed Warning to advise health care professionals and patients about the risk of developing capillary leak syndrome, a condition in which fluid and proteins leak out of tiny blood vessels into surrounding tissues. Symptoms of capillary leak syndrome include difficulty breathing, weight gain, hypotension, or swelling of arms, legs and/or face. The Boxed Warning also notes the risk of hemolytic uremic syndrome, a condition caused by the abnormal destruction of red blood cells.1
According to the FDA, patients also 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. Women who are breastfeeding should not be given Lumoxiti.1
- FDA approves new kind of treatment for hairy cell leukemia [news release]. Silver Spring, MD; September 13, 2018: FDA website. http://www.pharmacytimes.com/link/218. Accessed September 14, 2018.
- US FDA approves Lumoxiti (moxetumomab pasudotox-tdfk) for certain patients with relapsed or refractory hairy cell leukaemia [news release]. Wilmington, DE; September 13, 2018: AstraZeneca. https://www.astrazeneca-us.com/media/press-releases/2018/us-fda-approves-lumoxiti-moxetumomab-pasudotox-tdfk-for-certain-patients-with-relapsed-or-refractory-hairy-cell-leukemia-09132018.html. Accessed September 14, 2018.