Dostarlimab - Uses, Dosage, Precautions, and Side Effects

Introduction:

Dostralimab is a monoclonal antibody drug that was principally developed by a biotech company in Massachusetts which was earlier known as Tessaro. GlaxoSmithKline later took over this company in 2019. Dostralimab is a recently discovered drug that has proven effective in treating rectal cancer. It is an injectable drug indicated for adults suffering from endometrial cancer (cancer in the lining of the uterus) that has progressed or recurred after the patient was treated with chemotherapy and other medications. It does not eradicate the disease directly but strengthens the body's immune system and makes it capable enough to fight infections and slow down tumor growth.

As per the study reports, a small clinical trial was conducted on 18 rectal cancer patients for six months, and the doctors were astonished to find that all of them got cured of cancer. In April 2021, Dostralimab was approved for medical use in the European Union and the United States. However, the drug Dostralimab-gxly received approval from the U.S. Food and Drug Administration (FDA) on 17th August 2021 for the treatment of mismatch repair-deficient recurrent and advanced solid tumors, as indicated by the FDA approved test. Studies and clinical trials have reported that this drug is a boon for those suffering from cancer that progressed even after the treatment. There were no alternative treatment options available to save their lives.

How Does Dostralimab Work to Treat Cancer?

Cancer survivors usually show uncontrolled cell growth due to genetic mutations or other defects. In simple terms, Dostralimab harnesses the power of the immune system. It belongs to the class of monoclonal antibodies and is a programmed death receptor-1 (PD-1). The cancer cells express PD-L1 (programmed death-ligand 1) on their surfaces which binds to PD-1 on the T cells (natural immune cells of the human body). This reduces the ability of the immune cells to recognize and kill cancer cells. Dostralimab binds to PD-1 receptors on the T cells and blocks the interaction of PD-L1 with the body’s immune cells. As a result, the body's immune system identifies the cancer cells and inhibits tumor growth. Dostralimab helps restore the cytotoxic properties of the immune cells of the body.

What Are the Uses of Dostralimab?

Dostralimab is specifically used to treat adult patients with mismatch repair-deficient recurrent (dMMR) or advanced tumors. The uses of Dostralimab are listed below:

• Advanced Endometrial Cancer - When cancer originates from the uterus lining, it is known as endometrial cancer. It is also known as uterine cancer because it initiates in the cells forming the uterus lining. Dostralimab is indicated when cancer has progressed, and patients have received a platinum-containing regimen, but that has failed.

• Solid Tumors - A solid tumor is an abnormal mass of tissue that might be benign or malignant. According to the FDA-approved test, Dostralimab is indicated for solid tumors that have progressed further. Also, the patient has no alternative treatment options and has not shown satisfactory results from the prior treatments.

Information About the Drug Dosage and Patient Selection:

Patient Selection:

As per the FDA reports, only those patients must be selected for Dostarlimab whose tumor specimens show dMMR. It is because the effect of chemotherapy on test results of dMMR in patients with high-grade gliomas (a tumor of the brain and spinal cord) is still under research.

Dosage:

Four doses of 500 mg each are administered every three weeks. The subsequent dosage of Dostralimab is given three weeks after the fourth dose, and 1000 mg of the drug is administered every six weeks. Dostralimab is administered intravenously over 30 minutes.

Dosage Modifications:

No modifications in the dosage of Dostarlimab are required. Withhold Dotarlimab in patients showing severe immune-mediated adverse reactions (grade 3). Permanently discontinue the drug if the patient shows life-threatening immune-mediated adverse reactions (grade 4) and recurrent grade 3 reactions that require systemic immunosuppressive treatments. If the corticosteroid dose cannot be reduced below 10 mg or less within 12 weeks of initiating steroids, Dostarlimab must be permanently discontinued.

Drug Warning:

Dostarlimab is a monoclonal antibody that binds to PD-1 or PD-L1 receptors and blocks their pathways. As a result, the immune system gets stimulated because the drugs break peripheral tolerance and induce immune-mediated adverse reactions. These reactions might turn fatal and affect any organ or body tissue. Immune-mediated adverse reactions might occur at any time after using Dostarlimab. These reactions usually manifest when the patient is undergoing treatment with PD-1 or PD-l1 blocking antibodies but might appear even after the drug is discontinued. Early identification and treatment of immune-mediated adverse reactions are crucial to ensure the safety of the drug. The patient must be monitored closely for the signs and symptoms of immune-mediated adverse reactions, and liver function, thyroid hormone, and creatinine tests must be done during the treatment.

Use the drug carefully under the following conditions:

• Immune-Mediated Pneumonitis - Dostarlimab can induce immune-mediated pneumonitis, which might turn fatal. People taking PD-1 or PD-L1 blocking antibodies and who have received thoracic radiations previously are at a higher risk of developing pneumonitis. According to the data, grade 2 and grade 3 pneumonitis occurred in 1.4 % of the patients who received Dostarlimab. The drug had to be discontinued in 0.6 % of patients, so patients must be examined before the drug is administered.

• Immune-Mediated Colitis - Dostarlimab might cause fatal immune-mediated colitis. The immune response of the patient must be examined before administering this drug. Cytomegalovirus infection recurred in patients with corticosteroid-refractory immune-mediated colitis treated with Dostarlimab. If the patient reports corticosteroid-refractory colitis, repeat the infectious workup to rule out other conditions.

• Immune-Mediated Endocrinopathies:

  • Adrenal Insufficiency: Dostarlimab can cause primary or secondary adrenal insufficiency, so withhold or permanently discontinue the drug depending upon the severity of adrenal insufficiency. Patients with grade 2 or higher adrenal insufficiency should undergo hormone replacement therapy or other treatments as per the clinical guidelines.

  • Hypophysitis: Dostarlimab can induce immune-mediated hypophysitis, so the drug must be permanently discontinued if it becomes severe. The symptoms of hypophysitis include photophobia, headache, and obstructed visual field.

  • Thyroid Disorders: Dostarlimab can cause immune-mediated thyroid disorders, so a thyroid function test must be done before administering the drug. The thyroid disorders encountered in patients receiving Dostarlimab include thyroiditis, hypothyroidism, and hyperthyroidism. However, none of these disorders led to the discontinuation of the drug.

  • Type 1 Diabetes mellitus: Dostarlimab can induce type 1 diabetes mellitus with diabetic ketoacidosis. Hyperglycemia and blood glucose levels of the patient must be monitored before starting the drug. Withhold or permanently discontinue the drug in case of severe diabetes.

• Immune-Mediated Nephritis - Dostarlimab can cause immune-mediated nephritis and renal dysfunction, so a renal function test must be done before using this drug. Grade 2 nephritis occurred in 0.4 % of the patients receiving Dostarlimab. However, the drug was not discontinued, and the condition resolved after some time.

• Immune-Mediated Dermatologic Reactions - Dostarlimab can induce immune-mediated rash, dermatitis, bullous dermatitis, and Stevens-Johnson syndrome. Topical corticosteroids and emollients are enough to treat immune-mediated dermatologic conditions, but the drug can be discontinued based on the condition’s severity.

• Other Adverse Reactions - The following reactions occurred in less than 1 % of the patients receiving Dostarlimab:

  • Nervous System - Meningitis, encephalitis, myelitis, myasthenia gravis, nerve paresis, and autoimmune neuropathy.

  • Cardiovascular System - Myocarditis, pericarditis, and vasculitis.

  • Ocular Manifestations - Iritis, uveitis, and ocular inflammatory diseases.

  • Gastrointestinal Manifestations - Gastritis, duodenitis, and increased lipase and serum amylase levels.

  • Endocrine Manifestations - Hypoparathyroidism.

  • Other Reactions - Autoimmune hemolytic anemia, systemic inflammatory immune response, aplastic anemia, sarcoidosis, immune thrombocytopenia, and solid organ transplant rejection.

• Infusion-Related Reactions - Severe and life-threatening infusion-related reactions have been observed in patients taking the drug Dostarlimab. However, these reactions were observed in only 0.2 % of the patients, so the drug can be permanently discontinued, or the rate of drug infusion can be slowed down.

Dosage Modifications for Adverse Drug Reactions:

The table given below summarizes the drug modification for adverse drug reactions:

For Patients:

What Is Cancer?

The human body contains billions of cells that proliferate under genetic control. These cells divide rapidly to replace the infected or the lost cells. However, the problem arises when the body’s control mechanism stops working. As a result, the cells divide uncontrollably, and these abnormal cells outnumber the old cells. As a result, these cells coalesce and form a mass known as the tumor. This tumor might remain confined to the affected organ (benign) or spread to the nearby organs (cancerous). The possible treatment options for cancer include radiotherapy, chemotherapy, and surgical excision of the tumor. However, these treatment options have numerous side effects, and some of them might be out of the patient’s reach.

What Are the Symptoms of Cancer?

The patient might experience the following symptoms of cancer:

• Fatigue.

• Weight changes.

• Swelling or thickening of the skin.

• Yellowing or darkness of the skin.

• Skin sores that do not heal.

• Change in bowel and bladder habits.

• Respiratory and swallowing difficulties.

• Persistent muscle or joint pain.

• Unexplained bleeding.

Some Basic Information About Dostarlimab:

What Is the Most Important Information About Dostarlimab?

Dostarlimab is a medicine that assists the immune system in working against cancer. However, it might stimulate the immune system to target the body's normal organs and tissues and affect how they work. This situation can become life-threatening or severe and cause death. The patient might encounter one or more of these problems at any time during or after the treatment. Sometimes, the patient faces the problem even after the treatment has ended.

Is Dostarlimab Indicated for All Types of Cancer?

Dostarlimab is a prescription drug used to treat adults suffering from cancer whose laboratory specimens have shown mismatch repair deficient (dMMR) or solid tumors. This drug is mainly indicated when cancer has recurred, has spread, is in the advanced stage, and cannot be removed surgically.

Dostralimab is usually recommended for the following conditions:

1. Patients having uterine cancer or endometrial cancer that persists even after chemotherapy with platinum-containing drugs.

2. Patients have a solid tumor that has become severe and has spread to the surrounding organs during or after the treatment. Also, there are no alternative treatment options available to manage cancer.

Is the Drug Really Effective Against Cancer?

A clinical trial was done recently in 18 patients with rectal cancer who were kept on follow-up for six months. The trial results were miraculous, as 14 patients showed an excellent clinical response to phase 2 advanced rectal cancer. In addition, no evidence of cancer was found on the biopsy, digital rectal examination, magnetic resonance imaging (MRI), and positron emission tomography (PET) scan.

What Things Must the Patient Inform the Doctor Before Taking Dostrlimab?

Before taking Dostrlimab, the patient must inform the doctor if he or she:

1. Has problems related to the immune system like Crohn’s disease, lupus, and ulcerative colitis.

2. Is allergic to Dostarlimab or its ingredients.

3. Is taking over-the-counter drugs, vitamins, nutritional supplements, or other herbal products because the dose of these drugs might need to be altered. The doctor might also monitor the side effects and the drug interactions.

4. Has undergone an organ transplant previously.

5. Has or is likely to receive a stem cell transplant that requires donor’s cells (allogeneic transplant).

6. Has undergone radiation therapy in the chest region.

7. Has nervous disorders like myasthenia gravis or Guillain-Barre syndrome.

8. Is pregnant or planning to become pregnant because Dostralimab can harm the baby in the womb.

Guidelines For Pregnant Females:

• The doctor will do a pregnancy test before starting the drug.

• The pregnant female must use effective birth control methods during the treatment and four months after the last dose of Dostarlimab. Consult the doctor to know about the birth control methods to be used during the treatment.

• The patient must inform the doctor immediately if she thinks she might become pregnant during the treatment.

• Lactating mothers or those planning to breastfeed the baby must inform the doctor because the drug might pass into the baby from the milk.

• Avoid breastfeeding during the treatment and four months after the last dose of Dostarlimab.

How Will the Patient Receive Dostarlimab?

Dostarlimab is administered under the following steps:

1. The doctor will inject Dostarlimab into the veins of the patient through an intravenous line for over 30 minutes.

2. The drug is usually given every three weeks for the first four doses. After the fourth dose, the drug is given every six weeks.

3. The doctor will review the patient’s condition to decide the number of treatments he requires. The doctor might also order a blood test for the patient to check for the side effects.

4. If the patient misses his appointment with the doctor, he can always call the doctor and reschedule his appointment.

5. Dostarlimab-gxly injection might cause serious side effects during the intravenous infusion, so the doctor or the nurse will always monitor the patient.

6. The patient can immediately inform the doctor if he has a headache, dizziness, chills, flushing, shortness of breath, or chest pain.

7. The doctor will also provide the manufacturer’s patient information manual before starting the treatment. It contains all the information about the drug, so the patient must read it carefully.

When Should the Patient Contact the Doctor After Taking the Drug?

The patient must contact his doctor immediately if he develops any new signs and symptoms in addition to the ones listed below:

• Cough.

• Shortness of breath.

• Chest pain.

Intestinal Problems: The following problems might develop in the gastrointestinal tract:

• Diarrhea or accelerated bowel movements.

• Black, sticky, or tarry stools containing blood and mucus.

• Severe abdominal pain and tenderness.

Liver Problems: Please pay attention to the following liver problems:

• The skin or the whites of the eyes might appear yellowish.

• Dark or tea-colored urine.

• Nausea and vomiting.

• Pain on the right side of the abdomen.

• Bleeding or bruising might occur more than usual.

Problems Related to the Hormones and Gland:

• Unusual headaches that do not subside immediately.

• The eyes become sensitive to light.

• Eye problems.

• Irregular or rapid heartbeat.

• Increased perspiration or sweating.

• Extreme fatigue or tiredness.

• Weight changes (weight gain or loss).

• Feeling hungry or thirsty more than normal.

• Urinary frequency (urinating more than normal).

• Hair loss.

• Feeling cold.

• Constipation.

• Changes in the voice like the voice might become deeper.

• Dizziness.

• Fainting.

• Behavioral changes like forgetfulness, reduced sex drive, and irritability.

Kidney Problems:

• Change in the urine output and color.

• Blood in the urine.

• Swollen ankles.

• Loss of appetite.

Skin Problems:

• Skin itching and rashes.

• Blistering and peeling of the skin.

• Painful sores or ulcers in the mouth, nose, throat, and genital areas.

• Fever or flu-like symptoms.

• Swelling in the lymph nodes.

In addition to the above side effects, the patient might present with problems in the other tissues and organs, including the immune system.

Call the doctor immediately if any of the following problems is noted:

• Respiratory difficulties.

• Chest pain.

• Mental confusion and memory problems.

• Mood changes and sleepiness.

• Stiff neck.

• Hallucinations.

• Problems related to body balance.

• Numbness or tingling sensation in the arms or legs.

• Vision-related problems like double vision, blurry vision, light sensitivity, eye pain, or changes in eyesight.

• Severe muscle pain, cramps, or weakness.

• Bruising more than usual.

• Low red blood cell count.

Infusion Problems - The infusion reaction might be severe or life-threatening. The signs and symptoms of infusion reactions are listed below:

• Chills and shaking.

• Skin rash or itching.

• Flushing.

• Wheezing.

• Shortness of breath.

• Dizziness.

• The patient might feel giddy and faint.

• Fever.

• Pain in the neck and back.

Reactions Related to the Transplanted Organ -

The doctor will inform the patient about the signs and symptoms he would develop after taking Dostarlimab. The symptoms depend upon the type of organ transplant the patient had. Studies have reported that people who received a bone marrow or stem cell transplant from the donor cells (allogeneic transplant) are more likely to develop complications, including graft-versus-host disease. These complications are serious and might turn fatal. They can occur in patients who underwent organ transplantation before or after receiving Dostarlimab. Therefore, the doctor will constantly monitor the patient for these complications.

What Should Be Done to Avoid Serious Complications Due to Dostarlimab?

The doctor will examine the patient thoroughly and check for serious problems during treatment with Dostarlimab. Then, depending upon the symptoms, he might treat the patient with corticosteroid or other hormone replacement therapy. However, even after the treatment, the doctor might withhold or permanently stop the drug if the patient develops serious side effects or complications.

What Are Some of the Other Possible Side Effects of Dostarlimab?

The common side effects of Dostarlimab in patients with deficient mismatch repair (dMMR) solid tumors include the following:

1. Lethargy and weakness.

2. Anemia (reduced hemoglobin concentration).

3. Nausea and diarrhea.

4. Reduced white blood cell count.

5. Decreased albumin concentration in blood.

6. Elevated liver blood tests.

7. Reduced sodium concentration in blood.

Some Information About the Safety and Effective Use of Dostarlimab:

A medication guide is usually provided with the medicine to educate the patient about the drug, its uses, side effects, and benefits. But sometimes, the drug might be used for purposes other than those mentioned in the medication guide. For example, if a patient requires more information about Dostarlimab, he can contact the doctor who prescribed the drug. The patient can even know about the information written for doctors to get an insight into the drug.

Information for Doctors:

Description of Dostralimab:

Dostralimab is available under the trade name JEMPERLI and is a programmed death receptor-1 (PD-1) blocking IgG4 (immunoglobulin G4) humanized monoclonal antibody. This drug is produced in the Chines hamster ovary cells, and the calculated molecular weight of the drug is 144 kDa. Dostarlimab-gxly injection is clear, sterile, slightly opalescent, colorless or yellowish, and free from visible particles. The drug is supplied in single-dose vials.

Composition of Dostarlimab:

Active Ingredient:

Dostarlimab-gxly.

Inactive Ingredients:

As the drug is administered in a single-dose vial, each vial comprises 500 mg of Dostarlimab in 10 mL of the solution having a pH (potential of hydrogen) of six. So, each mL of the solution contains the following ingredients:

1. 50 mg of Doatralimab-gxly.

2. Citric acid monohydrate (0.48 mg).

3. L-arginine dihydrochloride (21.07 mg).

4. Polysorbate 80 (0.2 mg).

5. Sodium chloride (1.81 mg).

6. Trisodium citrate dihydrate (6.68 mg).

7. Water for injection.

Clinical Pharmacology of Dostralimab:

Mechanism of Action:

When the PD-1, PD-L1, and PD-L2 ligands bind to the PD-1 receptors on the T cells, they inhibit cytokine production and T cell proliferation. Activation of the PD-1 ligands in some tumors might disrupt the working of the T cells. As a result, the active T cells are prohibited from surveying and recognizing the tumor cells. This is the time when Dostarlimab comes into action. It is a humanized monoclonal antibody of immunoglobulin G4 isotype that attaches to the PD-1 receptors and blocks its interaction with PD-L1 and PD-L2. It blocks the PD-1 pathway-mediated inhibition of immune response and stimulates the anti-tumor immune response. A study on mouse tumor models discovered that blocking PD-1 activity results in decreased tumor growth.

Pharmacodynamics:

The pharmacodynamics and exposure-response relationship for the safety and efficacy of the drug has not been fully explained. However, Dostralimab directly binds to PD-1 receptors on the T cells, showing sustained target engagement and stimulated interleukin-2 (IL-2) production throughout the dosing interval.

Drug Distribution:

The total volume of distribution of Dostarlimab-gxly at a steady rate is approximately 5.3 L (14 %).

Drug Elimination:

The elimination half-life of Dostarlimab-gxly in the steady state is 23.5 days, and the mean clearance of the drug at a steady state is 0.007 L/h (30 %).

Drug Metabolism:

It is expected that Dostarlimab might get metabolized via the catabolic pathway into small peptides and amino acids.

Non-clinical Toxicology:

No studies have been done to evaluate the potential of Dostarlimab for carcinogenesis, mutagenicity, and impairment of fertility. When the animal studies were conducted to determine the effects of Dostralimab, no significant changes were noted related to fertility.

Preparation and Administration of the Drug:

Preparation for Intravenous Infusion of the Drug:

• Inspect the solution carefully for discoloration and particulate matter. Normally, the solution is clear to opalescent and colorless or yellowish.

• Discard the vial immediately if it contains visible particles.

• Avoid shaking or freezing the vial.

• If 500 mg of the drug is to be administered, withdraw 10 mL of Dostarlimab from the vial using a pre disposable polypropylene syringe. Dilute into an intravenous infusion bag comprising 0.9 % sodium chloride injection or 5 % dextrose injection to a final concentration in the range of 2 to 10 mg/mL. The infusion bag should be made of polyolefin, ethylene-vinyl acetate, or polyvinyl chloride with di (2-Ethylhexyl) phthalate (DEHP).

• If 1000 mg of the drug is to be administered, withdraw 20 mL or 10 mL of the drug from each of the two vials. Finally, dilute the drug in an intravenous bag containing 0.9 % sodium chloride injection or 5 % dextrose injection to a final concentration in the range of 4 to 10 mg/mL.

• Gently invert the syringe to mix the diluted solution and refrain from shaking the vial.

• Discard the vial immediately after use.

Storage of the Infusion Solution:

Make sure to store the drug in the original carton until the time of preparation to protect it from sunlight. The infusion solution can be stored in the following ways:

1. The drug must be stored at room temperature for not more than six hours, starting from the time of preparation until infusion.

2. The drug can also be refrigerated at temperatures between 2 and 8 degrees Celsius. However, make sure the drug returns to the normal temperature before infusion.

3. Discard the drug after 6 hours under room temperature and after 24 hours under refrigeration.

Administration of the Drug:

Dostralimab is an injectable drug, so it has to be administered carefully. The drug is given intravenously over 30 minutes utilizing an intravenous line. The line consists of tubing made of polyvinyl chloride, or platinum-cured silicone. The fittings are made of polyvinyl chloride or polycarbonate. A sterile, low protein binding, non-pyrogenic, and 0.2 micron inline or an additional filter is present along the line. Dostralimab should not be administered as an intravenous push or bolus injection. Ensure no other drug is administered along with Dostralimab through the same infusion line.

Drug Dosage Form and Strength:

Dostralimab is available as an injectable drug with a dosage strength of 500 mg/10 mL. It is a clear, opalescent, colorless, or yellowish solution in a single dose vial that must be administered intravenously after dilution.

Drug Storage and Handling:

Dostarlimab injection is a clear or opalescent, colorless, or slightly yellowish solution supplied in a single-dose vial. The drug is supplied in a carton containing a 500 mg/10 mL single-dose vial. The vial must be stored in a refrigerator at temperatures between 2 to 8 degrees Celsius. Store the vial in the original carton and keep it away from sunlight. Do not freeze or shake the vial as it might alter the properties of the drug.

Warnings and Precautions:

1. Severe and Fatal Immune-Mediated Reactions - Dostarlimab is a monoclonal antibody that can cause severe and life-threatening immune reactions. Avoid the drug in patients presenting with the following immune-mediated adverse reactions:

   • Immune-mediated pneumonitis.

   • Immune-mediated hepatitis.

   • Immune-mediated colitis.

   • Immune-mediated endocrinopathies like hypophysitis, adrenal insufficiency, and thyroid disorders.

2. Infusion-Related Reactions - Several life-threatening infusion reactions have been reported after using Dostralimab. Continuously monitor the patients for symptoms related to infusion reactions. Slow the drug infusion rate or permanently discontinue it in case of severe infusion reactions.

3. Complications of Hematopoietic Stem Cell Transplant (HSCT) - Dostralimab might produce serious complications in patients who have undergone stem cell transplantation during or after the treatment. The complications include hyperacute graft-versus-host disease (GVHD), chronic GVHD, hepatic veno-occlusive diseases, and steroid-requiring febrile syndrome. These patients must be kept on constant follow-ups, and the drug must be administered only after measuring the risk-benefit ratio.

4. Embryo-Fetal Toxicity - If Dostralimab is administered to a pregnant female, it can harm the fetus because of its typical mechanism of action. Studies have reported that Dostarlimab inhibits the PD-1 and PD-L1 pathways which can increase the risk of immune-mediated rejection of the developing fetus and cause fetal death. Therefore, inform the pregnant females about the risk of the drug. Also, females of reproductive age and planning to conceive must use effective contraceptive methods during and four months after the treatment with Dostarlimab.

What adverse reactions were seen in the patients after taking Dostarlimab?

The following adverse reactions were reported in less than 10 % of the patients who received Dostralimab:

• Endocrine Disorders - Hypothyroidism, hyperthyroidism, autoimmune thyroiditis, and adrenal insufficiency.

• Optic Disorders - Iridocyclitis, uveitis.

• General Disorders - Pyrexia, chills.

• Gastrointestinal Disorders - Acute pancreatitis, colitis, and enterocolitis hemorrhage.

• Urinary Tract Disorders - Nephritis, tubulointerstitial nephritis.

• Respiratory and Mediastinal Disorders - Pneumonitis.

• Skin and Subcutaneous Diseases - Rash, pemphigoid, and erythema.

• Procedural Complications - Infusion-related reactions.

• Hepatic Disorders - Hepatocellular injuries.

• Musculoskeletal Disorders - Myalgia.

Adverse Reactions in a Clinical Trial:

The safety of Dostarlimab was evaluated during the GARNET trial in 104 patients having advanced or recurrent dMMR endometrial cancer. Patients were administered four doses of Dostralimab 500 mg followed by 1000 mg every six weeks until disease progression or unacceptable toxicity. The following severe adverse reactions were seen in 34 % of the patients

• Sepsis.

• Acute kidney injury.

• Urinary tract infections.

• Acute kidney injury.

• Abdominal pain.

• Pyrexia.

Dostralimab was permanently discontinued in 5 % of the patients because of severe reactions like sepsis, bronchitis, and pneumonitis. The most common adverse reactions that were seen in more than 20 % are listed below:

• Fatigue.

• Asthenia.

• Nausea.

• Diarrhea.

• Constipation.

• Anemia.

The common grade 3 and grade 4 abnormalities that were seen in the laboratory specimens are listed below:

1. Decreased lymphocyte count.

2. Reduced sodium concentration.

3. Decreased leukocyte count.

4. Increased creatinine levels.

5. Decreased albumin concentration.

6. Increased alkaline phosphatase levels.

7. Elevated alanine aminotransferase levels.

Immunogenicity:

Immunogenicity can occur with any of the therapeutic proteins. The presence or absence of antibodies in the assay depends upon their sensitivity and specificity. Several factors determine antibody positivity in an assay, including sample handling, assay methodology, time of sample collection, underlying diseases, and concomitant medicines. Therefore, comparing the incidence of antibodies in a study of Dostarlimab and other drugs is not worth it. However, the immunogenicity was determined during the GARNET trial. During this trial, 384 patients received the drug, and 2.1 % of them showed treatment-emergent anti-drug antibodies. In contrast, neutralizing antibodies were found in 1 % of the patients. Only a small number of patients showed adverse drug reactions, so nothing could be concluded about the relationship between immunogenicity and the safety and efficacy of the drug.

Some More Facts About Dostarlimab:

Use of Dostarlimab in Specific Populations:

Pregnancy:

Dostarlimab must not be injected into a pregnant female because it can turn lethal for the fetus. There is no information available about the use of Dostarlimab in pregnant females. However, the problem might occur in pregnant females because the drug is a monoclonal antibody of the immunoglobulin G4 isotype. It is well-established that human IgG4 crosses the placental barrier and has access to the developing fetus. Therefore, Dostarlimab might possess the potential to harm the fetus.

Lactation:

Not much data is available regarding the presence of Dostarlimab in human breast milk or its effects on breast milk production. However, lactating mothers are advised not to breastfeed the child during the treatment and four months after the last dose of Dostarlimab.

Females and Males of Reproductive Age:

Females planning to conceive during or before the treatment must get a pregnancy test done to confirm their pregnancy status. In addition, they should use effective contraceptive methods during the treatment and four months after the last dose.

Pediatric Population:

Nothing has been discovered about the safety and efficacy of Dostarlimab in children.

Geriatric Population:

Dostarlimab was used to treat 515 patients; amongst them, 51 % were younger than 65 years, 37 % were between 65 and 75 years, and 12 % were above 75 years. However, no significant differences were noted related to the drug's effects, safety, and efficacy.

Clinical Trial:

Mismatch Repair-Deficient Recurrent or Advanced Endometrial Cancer:

The efficacy of Dostarlimab was studied during the GARNET (genomic and randomized trials network) trial. It is a multicohort, multicenter, and open-label trial conducted in patients with advanced-stage tumors. The trial was conducted on 71 patients with mismatch repair-deficient recurrent and advanced endometrial cancer, which progressed even after treatment with the platinum-containing regimen. The trial participants received four doses of Dostralimab 500 mg intravenously for three weeks, followed by 1000 mg for six weeks. The treatment continued unacceptable toxicity and disease progression. 66 % of the trial patients had stage 4 disease, while 90 % of them were undergoing anticancer surgery, and 79 % received anticancer radiotherapy. After the trial, the confirmed overall response rate was 42.3 %, and the partial response rate was 29.6 %.

Information About the Latest Clinical Trial:

A clinical trial was recently done on 18 patients suffering from rectal cancer at the Memorial Sloan Kettering Cancer Center in Manhattan, USA. The trial participants had locally advanced rectal cancer, meaning cancer had metastasized to the lymph nodes surrounding the rectum. Also, these patients had previously undergone radiotherapy, chemotherapy, invasive surgeries, and other treatments, but no satisfactory results were obtained. Dostarlimab was administered to the patients for six months during the trial according to the prescribed doses. The results of the trials were surprising as none of the patients showed cancer after physical examination, endoscopy, magnetic resonance imaging (MRI), and positron emission tomography (PET) scans.