Inotuzumab ozogamicin, sold under the brand name Besponsa, is a targeted therapy used in oncology. This medication is an antibody-drug conjugate, combining a monoclonal antibody with a potent chemotherapy agent. It is designed to act on particular cancer cells, representing a focused approach to cancer treatment.
How Inotuzumab Ozogamicin Works
Inotuzumab ozogamicin functions as a targeted delivery system due to its two-part structure. The first component is inotuzumab, a monoclonal antibody engineered to recognize and bind to the CD22 protein, which is present on the surface of most B-cell cancers. The antibody acts as a homing device, circulating through the body until it attaches to the CD22 protein on malignant B-cells.
Once the antibody binds to CD22, the cancer cell absorbs the drug complex through endocytosis. This brings the second component, ozogamicin, inside the cell. Ozogamicin is a powerful cytotoxic agent, a derivative of a natural substance called calicheamicin, which is too potent to be administered on its own. It is connected to the antibody by a specialized linker molecule.
Inside the cell’s acidic environment, the linker is cleaved, releasing the ozogamicin payload. The freed ozogamicin then travels to the cell’s nucleus, where it binds to the DNA.
This binding causes irreparable double-strand breaks in the DNA, triggering the cell to undergo programmed cell death, or apoptosis. This targeted mechanism delivers a highly toxic agent directly to cancer cells. It aims to reduce damage to healthy tissues that do not express the CD22 protein.
Approved Medical Uses
The U.S. Food and Drug Administration (FDA) has approved inotuzumab ozogamicin for adults and children one year and older with B-cell precursor acute lymphoblastic leukemia (ALL). Its use is indicated for patients whose cancer is either relapsed or refractory. “Relapsed” means the cancer has returned after remission, while “refractory” describes cancer that did not respond to previous treatments.
For adults, approval was based on its effectiveness in patients who had undergone one or two prior chemotherapy regimens. For patients with the Philadelphia chromosome genetic marker, the disease must have also failed to respond to at least one tyrosine kinase inhibitor.
This positions the drug as a therapeutic option when initial treatments have not been successful. The approval was expanded in March 2024 to include pediatric patients, addressing a need for this younger population with relapsed or refractory ALL.
The Treatment Process
Inotuzumab ozogamicin is administered as an intravenous (IV) infusion over one hour in a clinical setting. Patients are monitored by healthcare professionals during the infusion and for at least one hour afterward to watch for any immediate reactions.
Treatment is organized into cycles. The first cycle lasts three weeks, with doses on Day 1, Day 8, and Day 15. Subsequent cycles are extended to four weeks to allow for recovery. For patients who are candidates for a hematopoietic stem cell transplant, the recommended course of treatment is two cycles.
To minimize infusion-related reactions, patients receive premedications before each dose. This regimen includes a corticosteroid, an antipyretic to prevent fever, and an antihistamine. For individuals with a high number of leukemia cells, medication to reduce uric acid levels may also be given to prevent tumor lysis syndrome.
Potential Side Effects
Treatment with inotuzumab ozogamicin is associated with a range of side effects. Common adverse events include fatigue, nausea, headache, fever, and abdominal pain. A serious effect is myelosuppression, the suppression of bone marrow’s ability to produce blood cells. This can lead to low platelet counts (thrombocytopenia) and low white blood cell counts (neutropenia), increasing the risk of bleeding and infections. Regular complete blood counts (CBCs) are performed to monitor for myelosuppression.
The FDA has placed a black box warning on this medication for the risk of severe liver damage (hepatotoxicity), which is monitored with routine liver function tests (LFTs). A specific form of this is Veno-occlusive Disease (VOD), where small veins in the liver become blocked. This condition can lead to liver failure and may be fatal, with a higher risk for patients who undergo a hematopoietic stem cell transplant after treatment.
Other complications can include infusion-related reactions, which may cause fever and chills. The medication can also affect the heart’s electrical activity, causing a prolongation of the QT interval, which is monitored with electrocardiograms (ECGs). Due to these risks, treatment must be supervised by physicians experienced in cancer therapy.
Monitoring and Efficacy
Clinical studies have provided data on the efficacy of inotuzumab ozogamicin. The pivotal INO-VATE ALL trial showed that a significantly higher percentage of adult patients treated with this drug achieved complete remission compared to those receiving standard chemotherapy. In the primary analysis, 80.7% of patients in the inotuzumab ozogamicin group achieved remission, compared to 29.4% in the chemotherapy group.
Many patients who achieved remission also reached minimal residual disease (MRD) negativity, meaning no leukemia cells could be detected with sensitive tests. The two-year overall survival rate was 23% for patients treated with the drug, compared to 10% for those on standard chemotherapy.