1. Lovell, Alexandra PharmD, BCOP

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What is olutasidenib?

Olutasidenib is a small molecule inhibitor of isocitrate dehydrogenase-1 (IDH1). It can be used in acute myeloid leukemia (AML) that harbors this mutation. IDH1 mutations occur in 7-14 percent of patients with AML and this mutation can lead to impaired differentiation of progenitor cells.


How does olutasidenib work?

IDH1 mutations cause an increase in 2-hydroxyglutarate, which impairs normal cell differentiation. Olutasidenib inhibits mutant forms of IDH1, leading to decreased levels of 2-hydroxyglutarate, which in turn, restores normal differentiation of hematopoietic cells.


What is this approved for?

Olutasidenib is FDA-approved for the treatment of adults with relapsed or refractory AML with a susceptible IDH1 mutation as detected by an FDA-approved test.


What is the basis for this approval?

Olutasidenib was studied in 147 patients with relapsed or refractory AML with an IDH1 mutation. Patients received olutasidenib 150 mg orally twice daily until disease progression, unacceptable toxicity, or stem cell transplantation. About one-third of patients were primary refractory and there were two median prior lines of therapy. After a median follow-up of 10.2 months, 35 percent of patients achieved a complete response or complete response with a partial hematologic response. Of those that achieved this response, the median time to response was 1.9 months and the median duration of response was 25.9 months. About one-third of patients who were transfusion-dependent prior to initiating therapy became transfusion-independent.


How do you administer this drug?

Olutasidenib is an oral capsule and should not be broken, opened, or chewed. It should be administered at a dose of 150 mg orally twice daily until disease progression or unacceptable toxicity. Olutasidenib should be taken on an empty stomach at least 1 hour before or 2 hours after a meal. Doses should not be administered within 8 hours of each other.


Are there any pre-medications needed?

No pre-medications are needed prior to olutasidenib. This drug has minimal to low emetogenic potential; however, patients can take antiemetics if nausea or vomiting occurs.


What are the common side effects associated with olutasidenib (> or =20%)?

The most common adverse events are transaminitis, hypokalemia, hyponatremia, alkaline phosphatase elevations, nausea, increased serum creatinine, fatigue, malaise, arthralgia, constipation, increased lymphocytes, hyperbilirubinemia, leukocytosis, increased uric acid, dyspnea, pyrexia, rash, increased lipase, mucositis, and diarrhea.


What are the uncommon side effects associated with olutasidenib (less than 20%)?

Although uncommon, differentiation syndrome can be a severe side effect of olutasidenib. Abdominal pain, vomiting, edema, cough, decreased appetite, headache, and hypertension have also been reported.


Are there any important drug interactions I should be aware of?

Olutasidenib is a substrate of CYP3A4. Concurrent use of strong CYP3A4 inducers should be avoided. Olutasidenib is also an inducer of CYP3A4, CYP2B6, CYP1A2, CYP2C8, and CYP2C9, which may decrease concentrations of other drugs metabolized by this pathway.


How do I adjust the dose in the setting of renal or hepatic insufficiency?

No dose adjustments are needed in patients with mild-to-moderate renal dysfunction or hepatic impairment. Olutasidenib was not studied in patients with severe renal or hepatic impairment. In patients with hepatic dysfunction, monitor for increased risk of differentiation syndrome.


What should my patients know about olutasidenib?


* Differentiation syndrome is a life-threatening adverse effect that can occur when treated with olutasidenib. Patients should contact their provider immediately if they experience shortness of breath, cough, fever, edema, weight gain, decreased urination, lightheadedness, or dizziness.


* Hepatotoxicity can occur while taking olutasidenib. Patients should report any right upper abdominal pain, dark urine, jaundice, anorexia, or fatigue.


* There are many drug interactions with this medication. Patients should discuss starting or stopping any medications with their health care provider.


What other information should I know about olutasidenib?


* Differentiation syndrome with olutasidenib can occur as soon as 1 day or 18 months after initiation. Olutasidenib should be held and systemic corticosteroids started until resolution of symptoms (minimum 3 days). Olutasidenib can be resumed after resolution of differentiation syndrome.


* Response to this drug may take time. Treatment should continue for a minimum of 6 months to allow for clinical response.


What useful links are available regarding olutasidenib?


* Prescribing information:


* Patient education guide:


* Research studies to watch: Lancet Haematol 2023; doi: 10.1016/S2352-3026(22)00292-7, J Clin Oncol 2021; doi: 10.1200/JCO.2021.39.15_suppl.7006


Are there any ongoing clinical trials related to olutasidenib?

Olutasidenib is also being studied in patients with advanced solid tumors and gliomas harboring an IDH1 mutation. More information is available about the trial at


ALEXANDRA LOVELL, PHARMD, BCOP, is Clinical Pharmacy Specialist in Leukemia at the University of Texas MD Anderson Cancer Center. JANELLE E. MANN, PHARMD, BCOP, is Clinical Oncology Pharmacist/Manager, Clinical Pharmacy Services at Washington University School of Medicine. She serves as the Pharmacy Forum column editor. RAMASWAMY GOVINDAN, MD, Professor of Medicine; Anheuser Busch Chair in Medical Oncology; Director, Section of Medical Oncology, Division of Oncology, Washington University School of Medicine, serves as the Pharmacy Forum column physician advisor.

Alexandra Lovell, Ph... - Click to enlarge in new windowAlexandra Lovell, PharmD, BCOP. Alexandra Lovell, PharmD, BCOP
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