Moxetumomab pasudotox, marketed under the brand name Lumoxiti, is a targeted cancer therapy developed to address a specific and rare form of leukemia. It belongs to a class of treatments known as antibody-drug conjugates, which are engineered to deliver a potent cell-killing agent directly to cancerous cells while largely sparing healthy ones.
The U.S. Food and Drug Administration (FDA) approved the medication in September 2018 for a distinct patient population. However, the manufacturer later announced the decision to discontinue the marketing of Lumoxiti in the United States and the European Union for commercial reasons, citing limited use. This discontinuation was not related to new concerns about the drug’s safety or its effectiveness in its approved use.
How Moxetumomab Pasudotox Works
The function of moxetumomab pasudotox is based on its two-part structure, which combines precise targeting with a powerful cytotoxic, or cell-killing, payload. The first component, “moxetumomab,” is a targeting protein derived from a monoclonal antibody. This part is engineered to act like a homing device, specifically seeking out and binding to a protein called CD22. The CD22 protein is found in high numbers on the surface of the specific B-cells that become cancerous in hairy cell leukemia.
Once the moxetumomab portion of the drug attaches to the CD22 protein on a cancer cell, the bound drug is pulled into the cell’s interior through endocytosis. This internalization allows the second component, “pasudotox,” to be released inside the malignant cell. This toxin is a modified version of a potent bacterial poison known as Pseudomonas exotoxin A (PE38).
After being released inside the cell, the pasudotox component becomes active and disrupts the machinery the cell needs to live. It works by shutting down the cell’s ability to manufacture new proteins, a process necessary for cell survival. The toxin accomplishes this by inactivating a molecule called elongation factor 2, which is part of protein synthesis. Unable to produce these proteins, the cancer cell undergoes programmed cell death, known as apoptosis.
Medical Use for Hairy Cell Leukemia
Moxetumomab pasudotox is indicated for the treatment of hairy cell leukemia (HCL), a rare and slow-growing cancer of the blood and bone marrow. HCL is characterized by the overproduction of abnormal B-lymphocytes, a type of white blood cell. Under a microscope, these cancerous cells have fine, hair-like projections on their surface, which gives the disease its name.
The therapy is not an initial treatment for HCL. Its use is reserved for adult patients with relapsed or refractory HCL. Relapsed disease means the cancer has returned after treatment, while refractory disease means the cancer did not respond to it initially.
Prescribing guidelines narrow its use to patients who have undergone at least two systemic therapies, one of which must have been a purine nucleoside analog (PNA). This positioning makes it an option for patients whose cancer has persisted despite multiple established treatments.
Treatment Administration
Moxetumomab pasudotox is delivered through an intravenous (IV) infusion that takes approximately 30 minutes to complete in a clinical setting. This method ensures the treatment enters the bloodstream directly to find its target cancer cells.
A full course of treatment is organized into 28-day cycles, with the patient receiving the infusion on days 1, 3, and 5. This schedule may be repeated for up to six cycles, depending on the patient’s response and tolerance. Treatment may be stopped sooner if the disease progresses or if unacceptable side effects develop.
To reduce the risk of infusion reactions, patients receive intravenous hydration before and after the infusion. About 30 to 90 minutes before administration, patients are premedicated with an antihistamine, acetaminophen, and a histamine-2 receptor antagonist.
Significant Side Effects and Safety Information
Moxetumomab pasudotox has two black box warnings from the FDA, the most serious type of warning on a prescription drug’s label. The first risk is Capillary Leak Syndrome (CLS), which occurs when fluid and proteins leak from small blood vessels into surrounding tissues. This leads to symptoms like significant weight gain, swelling, a drop in blood pressure, and a decrease in the blood protein albumin.
The second black box warning is for Hemolytic Uremic Syndrome (HUS). HUS is a serious condition characterized by a combination of three problems: the destruction of red blood cells, a low platelet count which can affect blood clotting, and acute kidney failure. Both CLS and HUS are potentially life-threatening and require immediate medical attention. The risk of these events led to the recommendation to permanently discontinue the drug if a patient develops HUS or a severe case of CLS.
Due to these risks, patients require close monitoring. Before each infusion, healthcare providers check the patient’s weight and blood pressure for early signs of CLS. Regular blood tests are also performed to monitor kidney function, as well as to check hemoglobin and platelet counts for any indication of HUS.
More common adverse reactions include swelling in the limbs (peripheral edema), nausea, fatigue, headache, and fever. Electrolyte abnormalities, such as low levels of calcium in the blood, have also been noted.