Loncastuximab tesirine represents a modern approach in cancer treatment, designed to precisely target malignant cells. This medication is an antibody-drug conjugate, a type of therapy that combines the specificity of an antibody with the cell-killing power of a chemotherapy drug. It offers a way to deliver potent treatment directly to cancer cells, aiming to reduce harm to healthy tissues.
What Loncastuximab Tesirine Is and How It Functions
Loncastuximab tesirine is an antibody-drug conjugate (ADC) that merges two distinct components. The first is loncastuximab, a humanized monoclonal antibody engineered to recognize and attach to CD19. CD19 is a protein found on the surface of certain cancer cells, particularly those in B-cell lymphomas, and is expressed in most B-cell related malignancies.
The second component is tesirine, a potent chemotherapy drug (SG3199). This drug is attached to the antibody via a stable linker. This allows for targeted delivery, minimizing exposure to healthy cells.
Once the loncastuximab antibody binds to the CD19 protein on the cancer cell’s surface, the entire antibody-drug conjugate is internalized into the cell. Inside the cell, the protease-sensitive linker connecting the antibody and the chemotherapy drug is cleaved. This cleavage releases the active chemotherapy payload, SG3199, directly into the cancer cell’s interior.
Upon release, SG3199 travels to the cell’s nucleus, where it binds to the minor groove of the DNA. It forms DNA interstrand cross-links that prevent the DNA from properly replicating and transcribing. This disruption of DNA blocks cell division and ultimately leads to programmed cancer cell death, a process known as apoptosis. This targeted delivery mechanism enhances the drug’s effect on tumors while limiting damage to non-cancerous cells.
Medical Conditions Treated
Loncastuximab tesirine is approved for treating specific types of cancer, primarily focusing on certain lymphomas that have not responded to previous treatments or have returned after initial therapy. It received accelerated approval from the U.S. Food and Drug Administration (FDA) in April 2021 and in the EU in December 2022.
The medication is indicated for adult patients with relapsed or refractory large B-cell lymphoma after they have received two or more prior systemic therapies. This includes diffuse large B-cell lymphoma (DLBCL) not otherwise specified, as well as DLBCL that has developed from a low-grade lymphoma. It is also approved for high-grade B-cell lymphoma.
DLBCL is a diverse subtype of non-Hodgkin lymphoma, and for patients whose disease has relapsed or is refractory, treatment options have historically been limited. Loncastuximab tesirine offers an additional therapeutic avenue for these individuals, particularly after multiple lines of previous treatment have failed. Its use is being explored in other B-cell malignancies as well.
Receiving Loncastuximab Tesirine
Loncastuximab tesirine is administered intravenously, meaning it is delivered directly into a patient’s vein through an infusion. This process typically takes about 30 minutes for each infusion. The treatment is usually given in a hospital or clinic setting under the supervision of healthcare professionals.
The recommended dosing schedule involves an initial higher dose for the first two treatment cycles, followed by a lower dose for subsequent cycles. Patients generally receive 0.15 mg/kg every three weeks for the first two cycles. After these initial cycles, the dose is typically reduced to 0.075 mg/kg and administered every three weeks.
Treatment continues until there is evidence of disease progression or if the patient experiences unacceptable side effects. Before each infusion, patients are usually given premedication, such as dexamethasone, to help reduce the risk of certain reactions. Dexamethasone is typically administered orally or intravenously twice daily for three days, starting the day before the loncastuximab tesirine infusion.
Managing Potential Side Effects
Patients receiving loncastuximab tesirine may experience a range of side effects, some of which can be serious, and monitoring by healthcare professionals is important throughout treatment. Common side effects include fatigue, which can be persistent and may require adjustments to daily routines. Nausea, vomiting, and diarrhea are also frequently reported gastrointestinal issues, often managed with dietary changes and anti-nausea medications.
Fluid retention, or edema, is another common side effect, presenting as swelling in the extremities, face, or general puffiness. This can sometimes lead to more serious conditions like pleural effusion (fluid around the lungs) or pericardial effusion (fluid around the heart), which require immediate medical attention if symptoms such as shortness of breath or chest pain develop. Skin reactions, including rashes and photosensitivity (increased sensitivity to sunlight), have also been observed, ranging from mild to severe. Patients should minimize sun exposure and report any new or worsening skin changes to their healthcare provider.
Myelosuppression, a reduction in blood cell counts, is a significant concern and includes neutropenia (low white blood cells), thrombocytopenia (low platelets), and anemia (low red blood cells). Neutropenia increases the risk of infections, so patients should watch for fever, chills, or other signs of infection and seek prompt medical care. Low platelet counts can lead to increased bruising or bleeding, requiring caution with activities that might cause injury. Liver enzyme elevations have also been noted, indicating potential liver toxicity, and these are closely monitored through blood tests.