A Comprehensive Review on Inotuzumab Ozogamicin

Overview

One example of a targeted leukemia treatment is Inotuzumab Ozogamicin, which is developed to directly target cancer cells while causing the least amount of harm to healthy cells. Treatment choices should be determined in cooperation with a healthcare professional and customized to the specific needs of each patient. Inotuzumab Ozogamicin was approved by the FDA (Food and Drug Administration) on the 17th of August 2017 for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

Indications of Inotuzumab Ozogamicin

Adults with relapsed or resistant B-cell precursor acute lymphoblastic leukemia (ALL) are the target population for Inotuzumab Ozogamicin therapy.

• B-Cell Precursor Acute Lymphoblastic Leukemia (ALL): Inotuzumab Ozogamicin is specifically used to treat B-cell precursor acute lymphoblastic leukemia (ALL), a subtype of acute lymphoblastic leukemia. White blood cell cancer ALL develops from immature B-cells, and B-cell precursor ALL is a subtype of ALL that affects the white blood cells. Rapidly expanding aberrant lymphoblasts in the bone marrow and blood are its defining feature.

• Relapsed or Refractory: The drug is recommended for adults with B-cell precursor ALL who have either experienced a relapse or have been intolerant to initial therapy (refractory). Refractory denotes that the leukemia cells did not respond to previous treatment or that the response was transient, and relapsed denotes that the disease has returned following a time of remission.

For Patients

Why Is Inotuzumab Ozogamicin Prescribed?

Adults with relapsed or resistant B-cell precursor acute lymphoblastic leukemia (ALL) are treated with Inotuzumab Ozogamicin. Patients who have not responded to prior treatment or who have had a relapse following a period of remission are specifically advised to take it. The following justifies the use of Inotuzumab Ozogamicin in this situation:

• Relapsed or Refractory B-Cell Precursor ALL: The fast growth of aberrant B-cell lymphoblasts in the bone marrow and blood is the hallmark of ALL, a form of acute lymphoblastic leukemia. Treatment for ALL gets more difficult when it recurs (relapses) or does not respond to early therapy (is resistant). In these circumstances, the drug Isotuzumab Ozogamicin is prescribed as a therapy option.

• Targeted Therapy: Inotuzumab Ozogamicin is a type of targeted treatment. It combines a cytotoxic substance (Ozogamicin) with a monoclonal antibody (Inotuzumab) that particularly targets CD22, a protein present on the surface of B-cell lymphoblasts. The cytotoxic medicine can be delivered to leukemia cells only through this combination, sparing healthy cells.

• Selectivity: Inotuzumab Ozogamicin works to reduce side effects associated with conventional chemotherapy by concentrating on leukemia cells that express the CD22 protein while causing the least amount of harm to healthy cells. This focused strategy aims to improve the treatment's safety profile while increasing its efficacy.

• Treatment Response: In patients with relapsed or resistant B-cell precursor ALL, Inotuzumab Ozogamicin may cause remission or a sizable decrease in leukemia cell counts. Remission is a crucial objective in the management of ALL because it can enhance outcomes and possibly act as a transitional stage to potentially curative therapies like stem cell transplantation.

• Enhancing Overall Survival: When compared to normal chemotherapy, Inotuzumab Ozogamicin has shown efficacy in clinical studies for select patient populations, improving overall survival for patients with relapsed or refractory ALL.

What Are the Food and Beverages to Avoid While Taking Inotuzumab Ozogamicin?

Following are some general dietary recommendations for cancer patients using chemotherapy or targeted medicines like Inotuzumab Ozogamicin:

• Hydration: Staying properly hydrated is crucial while receiving cancer therapy. A healthy kidney function can be maintained by drinking plenty of water.

• Diet: A balanced diet can improve general health and immunological function by containing a range of fruits, vegetables, lean meats, and whole grains. Maintaining a healthy diet is crucial, especially when treating cancer.

• Avoiding Specific Foods: Some cancer patients may have particular dietary preferences or limits due to side effects like nausea, taste alterations, or mouth sores.

• Alcohol: Due to potential drug interactions and potential immune system thinning effects, it is advised to limit or prevent alcohol consumption while receiving cancer therapy.

• Supplements: Talk to the doctor about taking dietary supplements such as vitamins or minerals. Supplements can interact with drugs or change how well a patient responds to treatment.

What Are the Side Effects of Inotuzumab Ozogamicin?

Inotuzumab Ozogamicin can have a variety of adverse effects, and each person will experience these side effects differently in terms of their severity and frequency. Potential adverse effects should be understood by patients, who should also address them with their healthcare professional. Inotuzumab Ozogamicin is frequently associated with the following side effects and adverse reactions:

• Inotuzumab Ozogamicin-Related Reactions: These reactions might happen during or right after the administration of the medication. Fever, chills, hypotension (low blood pressure), and respiratory symptoms are a few examples. Pre-medications are frequently given by healthcare professionals to help manage these reactions.

• Myelosuppression: Neutropenia (low white blood cell count), thrombocytopenia (low platelet count), and anemia (low red blood cell count) are examples of myelosuppression, which is a decrease in blood cell counts. The likelihood of bleeding, infections, and exhaustion may all rise as a result.

• Electrocardiogram (ECG) QT Interval Prolongation: Inotuzumab Ozogamicin may cause the QT interval to lengthen. Arrhythmias (disturbances in cardiac rhythm) can result from a prolonged QT interval.

• Headache: While using this drug, some people may have headaches.

• Fever: Inotuzumab Ozogamicin-induced fever is possible.

• Abdominal Discomfort: As a side effect, abdominal discomfort is possible.

• Fatigue: Inotuzumab Ozogamicin and other cancer therapies frequently cause fatigue as a side effect.

• Secondary Malignancies: Patients receiving Inotuzumab Ozogamicin have been reported to develop secondary malignancies, such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).

For Doctors

Mechanism of Action of Inotuzumab Ozogamicin

The monoclonal antibody, Inotuzumab Ozogamicin, is used to treat acute lymphoblastic leukemia (ALL), more especially B-cell precursor ALL. Its mode of action combines the chemotherapeutic agent's cytotoxic effects with a monoclonal antibody's capacity for targeting. The breakdown of its mode of operation is as follows:

• Monoclonal Antibody Targeting (Inotuzumab): Inotuzumab Ozogamicin is made up of two primary parts. The first element is the monoclonal antibody Inotuzumab. Monoclonal antibodies are proteins that have been designed to specifically bind to certain proteins or antigens on the surface of cancer cells, preserving healthy cells in the process.

• Targeting CD22: An antigen or protein called CD22, which is expressed on the surface of B-cell precursor ALL cells, is the specific target of the drug Inotuzumab. CD22 is a prime target for therapy since it is largely located on B-cells, particularly malignant B-cells.

• Antibody-Drug Conjugate (ADC): Inotuzumab is supplied as a component of an antibody-drug combination (ADC), not by itself. This indicates that it is connected to the chemotherapeutic drug Ozogamicin by a reliable linker molecule.

• Internalization: The complex is taken up by the leukemia cell once Inotuzumab attaches to CD22 on the surface of B-cell precursor ALL cells.

• Release of Ozogamicin: The stable linker molecule is disassembled inside the cancer cell, resulting in the release of Ozogamicin. A powerful cytotoxic or cell-killing substance is Ozogamicin.

• Cytotoxic Effect: Ozogamicin belongs to the calicheamicin medication class, which has potent DNA damaging capabilities and a cytotoxic effect. When Ozogamicin is released inside the leukemia cell, it attaches to DNA and breaks the DNA strands, which prevents the cell from reproducing and finally results in cell death.

• Selective Cancer Cell Destruction: The selective death of leukemia cells while limiting harm to healthy cells is made possible by the combination of Inotuzumab's precise targeting of CD22 and the release of the cytotoxic Ozogamicin inside the cancer cell. This focused strategy aims to improve therapeutic efficacy and lessen the negative effects of conventional chemotherapy.

Dosage and Forms

Depending on the unique characteristics of each patient, the particular treatment protocol, and the prescribing doctor's recommendations, the dosage and forms of Inotuzumab Ozogamicin may change. It is important to adhere to the healthcare provider's exact dose recommendations.

• Dosage: Inotuzumab Ozogamicin is given as an intravenous (IV) infusion, and the dosage normally depends on body weight. Depending on the precise treatment plan, the patient's general health, and how they react to the drug, the dose schedule may change. It is normally administered in cycles, each cycle containing a number of doses.

• Forms: Inotuzumab Ozogamicin is a liquid drug that is diluted and given as an IV infusion. It is available as a concentrated solution for infusion. Healthcare experts will prepare and administer the drug in a clinical setting, such as a hospital or infusion center. The medication is often provided in vials or single-dose vials. This drug is available in single-dose vials, each vial containing 0.9 mg Inotuzumab Ozogamicin as a lyophilized powder (undergoes reconstitution before administration).

Dosage and Administration

A specific amount of milligrams (mg) per square meter of body surface area (mg/m2) is frequently used to represent the usual recommended dosage. Depending on the patient's unique characteristics, such as weight and general health, as well as the treatment plan, the precise dose and dosing schedule may change.

Administration: When Inotuzumab Ozogamicin is administered, it enters the body through a vein and is given as an intravenous (IV) infusion. A healthcare practitioner often administers the medication in a clinical setting, such as a hospital, infusion facility, or clinic. Here are some crucial details about the administration:

1. Preparation: A healthcare professional must dilute the drug before infusion because it is delivered in a concentrated form. The right dosage must be ensured, and the danger of problems must be minimized through proper dilution and preparation.

2. Infusion: Over a predetermined amount of time, the diluted solution is gradually infused into a vein. The infusion procedure could take several hours to finish, and it is typically administered on a set basis, such as once a week.

3. Monitoring: Healthcare professionals attentively watch patients both during and after the infusion for any negative responses or side effects. This includes routine blood testing and vital sign checks.

4. Treatment Cycles: Inotuzumab Ozogamicin is frequently given in cycles. Multiple doses given over a predetermined number of days may make up a cycle. The patient's response and the treatment plan will determine how many cycles and how long the treatment will last.

5. Precautions: To help minimize potential adverse effects, including responses to infusions or nausea, patients may be premedicated with drugs.

Contraindications

• Hypersensitivity: Individuals with a known hypersensitivity (allergic response) to the active ingredient (Ozogamicin) or any of the other ingredients in the formulation should not take Inotuzumab Ozogamicin.

• Concurrent Use With Bleomycin: Inotuzumab Ozogamicin should not be administered concurrently with Bleomycin since it could cause pulmonary damage.

Precautions

• Liver Function: Inotuzumab Ozogamicin can have an impact on liver function, so patients who already have liver disease or have impaired liver function should use caution when receiving it. Monitoring of liver function tests is advised while receiving therapy.

• Infusion-Related Reactions: Fever, chills, and hypotension are examples of infusion-related events that can happen when Inotuzumab Ozogamicin is administered. During the infusion, patients should be properly watched, and the right steps should be taken to treat these reactions.

• Contraception and Pregnancy: Inotuzumab Ozogamicin may harm a developing fetus. Effective contraception must be used throughout therapy and for at least 8 months following the final dose. Use during pregnancy is not advised unless the possible advantages outweigh the dangers.

• Breastfeeding: Breastfeeding is not advised during therapy and for at least two months following the last dosage because it is unknown whether Inotuzumab Ozogamicin is excreted in breast milk.

• Infections: Due to Inotuzumab Ozogamicin's impact on white blood cell counts, patients may be at an increased risk of infections. It's crucial to keep an eye out for infection symptoms and administer the proper care.

• Bleeding: Low platelet counts brought on by Inotuzumab Ozogamicin may increase the risk of bleeding. The danger should be reduced by taking precautions and monitoring patients for bleeding symptoms.

• Secondary Malignancies: Patients receiving Inotuzumab Ozogamicin have been reported to develop secondary malignancies (new cancers). It is important to carefully weigh the benefits and potential hazards of a course of treatment.

Use in Specific Populations

Due to potential safety issues, the use of Inotuzumab Ozogamicin in particular populations, such as pregnant women, breastfeeding mothers, children, and people with particular medical conditions, should be carefully considered. Considerations for using Inotuzumab Ozogamicin in particular populations are listed below:

1. Pregnant Women:

• Contraindication: Inotuzumab Ozogamicin is not recommended for usage during pregnancy because it could harm a fetus that is still developing.

• Contraception: Use effective contraception during therapy and for at least eight months following the final dose if it is for a woman of reproductive potential.

2. Breastfeeding Women:

• Contraindication: Breastfeeding is contraindicated while receiving Inotuzumab Ozogamicin treatment and for at least two months after the final dosage. If the drug is excreted in breast milk, it is unknown.

3. Pediatric Patients: Depending on age and medical history, Inotuzumab Ozogamicin's safety and efficacy in pediatric patients may change. A pediatric oncologist with experience treating childhood acute lymphoblastic leukemia should decide on the dosage and use for children.

4. Elderly Patients: Patients who are 65 years of age or older may be more susceptible to certain adverse effects, such as liver damage and bleeding. The patient's age and general health should be taken into account when dosing and monitoring.

5. Patients With Impaired Livers: As Inotuzumab Ozogamicin can influence liver function, patients with pre-existing liver disease or impaired liver function should be continuously monitored during treatment.

6. Patients With Infections: Due to its impact on white blood cell counts, Inotuzumab Ozogamicin may put patients at an elevated risk of infections. It is crucial to keep an eye out for infection symptoms and administer the proper care.

7. Patients With Bleeding Disorders:Low platelet counts brought on by Inotuzumab Ozogamicin can increase the risk of bleeding. Patients who have a history of bleeding issues or who are taking drugs that alter blood coagulation need to be watched carefully.

8. Patients With Secondary Malignancies: Patients receiving Inotuzumab Ozogamicin have reportedly developed secondary malignancies (new tumors). Particularly in individuals with a history of previous malignancies, the possible risks and advantages of the proposed course of treatment should be carefully considered.

9. Patients With Hypersensitivity: Inotuzumab Ozogamicin should not be administered to patients who have a history of hypersensitivity (allergic response) to the medication's active component or any of the other formulation ingredients.

10. Kidney Impairment: It has not been thoroughly investigated how renal dysfunction affects the pharmacokinetics of Inotuzumab Ozogamicin. It is important to monitor patients who have severe renal impairment since dosage modifications can be required.

Pharmacodynamics

The study of a drug's physiological actions, including its methods of action and the connection between the drug's concentration and its effects, is known as pharmacodynamics. Healthcare professionals can more accurately assess a medication's therapeutic efficacy and potential side effects by being aware of its pharmacodynamics, such as Inotuzumab Ozogamicin. Here are some important details about Inotuzumab Ozogamicin's pharmacodynamics:

• Targeted Action: Inotuzumab Ozogamicin is a targeted medication for the treatment of acute lymphoblastic leukemia (ALL) in patients with B-cell precursors. The protein or antigen CD22, which is expressed on the surface of B-cell precursor ALL cells, is its main target. The medication selectively targets leukemia cells by binding to CD22 on those cells.

• Cytotoxicity: The cytotoxic element of Inotuzumab Ozogamicin is Ozogamicin, a cytotoxic drug that belongs to the calicheamicin class. Ozogamicin is released when the ADC (antibody-drug conjugate) binds to CD22 and is absorbed by the leukemia cell.

• DNA Damage: Ozogamicin causes double-strand breaks in the DNA strands within the leukemia cell in order to exert its cytotoxic effects. The cell's capacity to divide and replicate is hampered by DNA damage, which ultimately results in cell death.

• Apoptosis Induction: The DNA damage that Ozogamicin causes sets off a chain of intracellular occurrences that result in apoptosis or planned cell death. The body uses the natural process of apoptosis to get rid of unhealthy or undesirable cells.

• Selective Cell Killing: Inotuzumab Ozogamicin kills leukemia cells while sparing healthy cells, minimizing the chance of collateral tissue damage. This is known as "selective cell killing." This focused strategy seeks to enhance therapeutic benefits while reducing adverse effects.

• Immunological Effects: Inotuzumab Ozogamicin may have immunological effects in addition to its direct cytotoxic effects. It might energize the immune system to find and destroy cancer cells.

• Pharmacodynamic Monitoring: Throughout treatment, healthcare professionals frequently keep an eye on the pharmacodynamic effects of Inotuzumab Ozogamicin. This may involve evaluating the patient's response to treatment using indicators such as a decline in leukemia cell counts, achieving complete remission, and the absence of minimum residual disease (MRD).

Pharmacokinetics

The study of a drug's absorption, distribution, metabolization, and excretion by the body is known as pharmacokinetics. It is crucial to comprehend the pharmacokinetics of a medication like Inotuzumab Ozogamicin since it enables medical professionals to choose the best dosage and track the drug's effects. An overview of Inotuzumab Ozogamicin's pharmacokinetics is provided below:

• Absorption: Inotuzumab Ozogamicin is infused intravenously (IV), so it enters the body straight into the bloodstream for absorption. This technique avoids the digestive system, ensuring quick and thorough absorption of the medicine.

• Distribution: Inotuzumab Ozogamicin is transported throughout the body after it enters the bloodstream. Blood flow to different tissues and the presence of other drugs in the bloodstream can affect how the medicine is distributed.

• Metabolism: Inotuzumab Ozogamicin is an antibody-drug conjugate (ADC), which combines Ozogamicin, a cytotoxic substance, with Inotuzumab, a monoclonal antibody that targets CD22. In contrast to tiny drugs, the monoclonal antibody component (Inotuzumab) is not considerably metabolized by the body. The ADC is absorbed into the cell once it attaches to its target (CD22) on the surface of B-cell precursor ALL cells.

• Ozogamicin Metabolism: After being released into the cancer cell, Ozogamicin, the cytotoxic component of Inotuzumab, passes through metabolism. It binds to DNA and breaks DNA strands to cause its cytotoxic effects. In cells, Ozogamicin undergoes numerous metabolic processes that are connected to the drug's mode of action.

• Excretion: Inotuzumab Ozogamicin's excretion is not well-documented in the literature that is currently available. The monoclonal antibody Inotuzumab and any Ozogamicin breakdown products are probably excreted from the body through a variety of processes, including metabolism, degradation, and excretion through the kidneys or liver.

Drug Interactions in Inotuzumab Ozogamicin

The effectiveness and safety of the medication can be impacted by drug interactions. Following are some general guidelines for Inotuzumab Ozogamicin medication interactions:

• Concomitant Chemotherapy: Inotuzumab ozogamicin is normally used as a single agent for the treatment of acute lymphoblastic leukemia (ALL) that has relapsed or proven to be resistant to treatment. Radiation therapy or concurrent chemotherapy may raise the risk of toxicity; thus, this should be carefully examined. Additive or synergistic toxicities may result from the use of different cytotoxic drugs.

• Drugs That Can Lengthen the QT Interval: Inotuzumab Ozogamicin can lengthen the QT interval on electrocardiograms (ECGs). When combined with Inotuzumab Ozogamicin, medications that also lengthen the QT interval, such as some antiarrhythmics, antipsychotics, and antibiotics, may increase the risk of QT prolongation. Patients using these drugs should have their electrolyte levels and ECGs monitored by healthcare professionals.

• Drugs Affecting Liver Function: Inotuzumab Ozogamicin, a drug that affects liver function, can have hepatotoxic effects. When used with Inotuzumab Ozogamicin, medications that influence liver function, such as several antifungal, antiviral, and antibiotic drugs, may raise the risk of liver damage. When administering such medications together, careful liver function monitoring is crucial.

• Antiplatelet and Anticoagulant Drugs: Thrombocytopenia brought on by Inotuzumab Ozogamicin can increase bleeding risk. The risk of bleeding may be significantly increased by concurrent use of antiplatelet medications (such as Aspirin and Clopidogrel) or anticoagulants (such as Warfarin and Heparin). Anticoagulant therapy patients should be regularly watched, and anticoagulant dosage modifications may be required.

• Immunosuppressive Agents: Inotuzumab Ozogamicin, an immunosuppressive agent, can impact the immune system and raise infection risk. The immune response may be further weakened by the concurrent use of immunosuppressive substances, such as corticosteroids or transplantation drugs. For patients using immunosuppressive medications, careful surveillance for infection symptoms is crucial.

• Potential for Drug-Drug Interactions: Drug interactions have the potential to be complicated and are not always predictable based only on the characteristics of the medications involved. Therefore, to identify and manage potential drug interactions, healthcare professionals should assess a patient's whole medication list, including prescription drugs, over-the-counter medications, herbal supplements, and nutritional supplements.

Drug Toxicity

Inotuzumab Ozogamicin's toxicity consists mostly of undesirable side effects that may develop while receiving treatment. This drug is used to treat acute lymphoblastic leukemia (ALL), and like many cancer treatments, it may have severe adverse effects that are both predictable and conceivably serious. The following list of Inotuzumab Ozogamicin toxicities is typical:

• Hepatotoxicity: Inotuzumab Ozogamicin can cause liver toxicity, including an increase in liver enzyme levels and potentially serious liver damage. During treatment, it is crucial to monitor liver function using blood tests.

• Infusion-Related Responses: During or soon after receiving Inotuzumab Ozogamicin, some patients may have infusion-related responses. The symptoms of these reactions can include fever, chills, hypotension (low blood pressure), and breathing issues. Pre-medications are frequently given by healthcare professionals to help manage these reactions.

• Myelosuppression: Inotuzumab Ozogamicin frequently causes myelosuppression as a side effect. It may result in anemia (low red blood cell count), thrombocytopenia (low platelet count), and neutropenia (low white blood cell count). The likelihood of bleeding, infections, and exhaustion may all rise as a result.

• Infections: Inotuzumab Ozogamicin can impair immunity, which raises the risk of infections. Patients using this drug should be constantly watched for any indications of infection; if this occurs, immediate antibiotic or antifungal treatment may be required.

• Hemorrhage: Inotuzumab Ozogamicin-related thrombocytopenia can increase the risk of bleeding. Patients should be closely watched for any indications of bleeding, and measures should be taken to reduce the risk, such as refraining from using drugs that interfere with platelet function.

• Electrocardiogram (ECG) QT Interval Prolongation: Inotuzumab Ozogamicin may cause the QT interval to lengthen. Arrhythmias (disturbances in the heart's rhythm) may result from this. Patients having a history of QT prolongation or those taking drugs that have an impact on the QT interval need to be watched carefully.

• Secondary Malignancies: Patients receiving Inotuzumab Ozogamicin have been reported to develop secondary malignancies, such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). It is important to carefully weigh the benefits and potential hazards of a course of treatment.

• Embryo-Fetal Toxicity: Inotuzumab Ozogamicin can be harmful to a developing fetus if given to pregnant women. Throughout treatment and for at least eight months following the final dose, effective contraception should be utilized.

• Nursing Mothers: Nursing mothers should avoid breastfeeding while receiving treatment and for at least two months following the final dosage because it is unknown if Inotuzumab Ozogamicin is excreted in breast milk.

• Other Adverse Effects: In addition to the aforementioned adverse effects, people may also experience nausea, headaches, fevers, lethargy, and abdominal pain.