1. Aschenbrenner, Diane S. MS, RN


* Ivosidenib (Tibsovo) has been approved to treat adults with relapsed or refractory acute myeloid leukemia who have a mutation in the IDH1 gene.



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The Food and Drug Administration has approved ivosidenib (Tibsovo), the first drug in the isocitrate dehydrogenase-1 inhibitor class, to treat adults with relapsed or refractory acute myeloid leukemia (AML) who have a mutation in the IDH1 gene. The IDH1 gene encodes the enzyme isocitrate dehydrogenase 1, found in the cytoplasm of many cells, which is crucial to many cellular processes.


In AML there is a loss of functioning red blood cells, white blood cells, and platelets. Approximately half of patients with AML have a form that is termed cytogenetically normal AML, meaning they have no major chromosomal abnormalities. About 16% of patients with cytogenetically normal AML have an IDH1 mutation. This mutation only occurs in cells that become cancerous. Instead of differentiating into other cells, immature cells with IDH1 mutations divide uncontrollably. Isocitrate dehydrogenase-1 inhibition decreases the proliferation of malignant cells and enables the formation of functioning, mature cells.


The most common adverse effects of ivosidenib (occurring in at least 20% of patients in a single-arm clinical trial) were fatigue, leukocytosis, arthralgia, diarrhea, dyspnea, edema in the arms or legs, nausea, mucositis, QT prolongation, rash, fever, cough, and constipation. Ivosidenib's labeling carries a boxed warning that the drug may lead to life-threatening differentiation syndrome anywhere from one day to three months after the start of treatment. In differentiation syndrome there is rapid proliferation and differentiation of myeloid cells (blood cells, such as granulocytes, monocytes, erythrocytes, and platelets, that are derived from common progenitor cells in the bone marrow). Signs and symptoms of differentiation syndrome include fever; dyspnea; acute respiratory distress; radiographic pulmonary infiltrates; pleural or pericardial effusions; rapid weight gain; peripheral edema; or hepatic, renal, or multiorgan dysfunction. In the clinical trial, 34 of 174 patients developed differentiation syndrome; 27 (79%) recovered after treatment or dose interruption. Ivosidenib's labeling also carries a warning that it may produce Guillain-Barre syndrome.


Nurses should confirm that assessment for IDH1 mutation, a baseline blood count, and a baseline blood chemistry assessment have been performed before the patient begins ivosidenib therapy. Because of the risk of adverse effects, nurses should impress on patients the importance of returning for required blood tests and electrocardiograms. If there are indications of drug toxicity, the prescriber should be consulted regarding a decrease in dosage. Specific information on dosage modification is provided in the drug's labeling. Patients who develop differentiation syndrome should be treated with a corticosteroid. Hydroxyurea therapy or leukapheresis may be necessary in some patients.


Ivosidenib is metabolized through the cytochrome P-450 (CYP) enzyme system. Nurses should determine whether any other medications patients are taking are CYP3A4 hepatic enzyme inhibitors. Strong or moderate CYP3A4 inhibitors will increase ivosidenib plasma concentrations and increase the risk of QT prolongation, and should be avoided. If such medications must be used, the dosage of ivosidenib should be adjusted. Conversely, strong CYP3A4 inducers will decrease ivosidenib plasma levels and can diminish the drug's effectiveness, and should be avoided. Other drugs that lengthen the QT interval should also be avoided, if possible, to minimize the risk of lethal cardiac rhythms.


Nurses should teach patients how to monitor for signs and symptoms of new-onset motor or sensory neuropathy, such as unilateral or bilateral weakness, sensory alterations, paresthesia, or difficulty breathing, which could be signs of Guillain-Barre syndrome. If symptoms appear, the patient should contact the prescriber.


Ivosidenib is administered orally at the same time every day, and tablets should not be split or crushed. Ivosidenib may be taken with or without food, although taking it with high-fat foods will elevate its blood concentration and increase the risk of adverse effects.


To read the full prescribing information for ivosidenib, see