Some people treated with dostarlimab can develop immune related liver injury.Some symptoms of liver injury or acute liver failure can include jaundice, pain in the upper right abdomen, ascites, nausea/vomiting, and disorientation or confusion. Pharmacology
Dostarlimab is a humanized IgG4 monoclonal antibody that was derived from a mouse antibody which was humanized via Complementarity Determining Region (CDR) grafting. Its serum half-life is 25.4 days.Other PD-1 antibodies included nivolumab (Opdivo) and pembrolizumab (Keytruda), both of which have uses in many different types of cancers which include classical Hodgkin lymphoma, renal cell carcinoma, and breast cancer. Another PD-1 antibody is cemiplimab (Libtayo) which was approved for treatment of squamous cell carcinoma, basal cell carcinoma and non-small cell lung cancer. Mechanism of action
Dostarlimab binds to the PD-1 receptor, with high affinity, to block its activity with PD-1 ligands (PD-L1) and PD-L2). PD-1 is a co-inhibitory receptor that is an important checkpoint protein for regulating T-cell tolerance. When PD-1 is constantly stimulated by PD-1 ligands, which are highly expressed in cancer cells, it allows cancer cells to dodge T-cell mediated immune responses. Therefore, blocking the binding of PD-1 to these ligands can allow T-cells to function normally and prevent tumor cells from bypassing immune surveillance. In mouse tumor models, it was shown that inhibiting PD-1 activity decreased tumor growth. Efficacy
In the GARNET Trial, dostarlimab achieved favorable results in decreasing the size of the tumor in those with endometrial cancer.
Side effects
Serious adverse reactions in >2% of patients included sepsis, acute kidney injury, urinary tract infection, abdominal pain, and fever (pyrexia).Immune-mediated adverse reactions can occur including pneumonitis, colitis, hepatitis, endocrine disease (endocrinopathies), and nephritis.The most common side effects reported while taking this medication during a trial were dyspnea, asthenia, fatigue, and nausea.Symptoms of overdose are similar to the side effect profile of the medication, so it could involve significant immune-mediated reactions. Immune-mediated adverse reactions
Dostarlimab is a monoclonal antibody that binds to PD-1 to block it from binding PD-1 ligands to remove inhibition of immune response. With this, it causes risk for immune-mediated adverse reactions. These reactions can be severe or fatal and occur in any part of the body: organs or tissues.Examples of immune-mediated adverse reactions include immune-mediated pneumonitis, colitis, hepatitis, adrenal insufficiency, hypophysitis, thyroid disorders, nephritis with renal dysfunction, and dermatologic reactions. Pregnancy and lactation
Dostarlimab can cause harm to a fetus. The death of the fetus can occur from the immune systems reaction to the fetus through the examination of its mechanism in animal studies. Dostarlimab is a human immunoglobulin G (IgG4), which could permeate through the placental barrier. This may risk harm to the developing fetus as the drug may be passed on from the mother.Data is not available regarding the presence of dostarlimab in breastmilk. Hepatotoxicity
Dostarlimab causes mild to moderate elevations to serum aminotransferase and alkaline phosphatase in 15-25% of recipients. Serum ALT elevation above five times the normal range occurs in 2-3% of recipients.