Acute myeloid leukemia (AML) is a rapidly spreading, deadly form of cancer that has infected an estimated 20,000 people in 2018. To slow this fast-acting killer, the Celgene Corporation created the isocitrate dehydrogenase 2 (IDH2) inhibitor Idhifa (enasidenib).
Known by its tradename Idhifa, enasidenib has assisted in fighting AML, the Food and Drug Administration (FDA) has some concerns that clinicians may not be following through in monitoring for some dangerous complications that can arise from the treatment, such as differentiation syndrome.
About Idhifa and AML
Acute myeloid leukemia is cancer developed in the bone marrow that creates mutated white blood cells called myeloid cells due to a rogue mutation int the marrow’s DNA. The “acute” in AML means that unlike “chronic” illnesses that grow slowly over time, AML spreads quickly throughout the body. This swiftness is evident in the fact that AML has claimed almost 11,000 lives in 2018 and bears a harrowing 27.4% survival rate according to the National Cancer Institute.
If not subdued continuously, AML can swiftly metastasize to the lymph nodes, liver, spleen, gonads, or even the spine or brain. Fortunately for patients with AML, Enasidenib can help keep the disease under control.
The oral medication from Celgene Corporation is more commonly known by its trade name, Idhifa, and is available for patients with isocitrate dehydrogenase-2 mutations that are detected by an FDA-approved test.
Enasidenib is an IDH2 inhibitor: meaning it halts the growth of cancerous myeloid cells by inhibiting the IDH2 protein, with a particular preference for the mutated form of the protein. Through this more targeted approach, doctors can create a more effective treatment with fewer side effects. That doesn’t mean, however, that Enasidenib doesn’t come with a few complications.
Idhifa Side Effects
Like any medication, there are various Idhifa side effects. Some of these risks are minor tradeoffs for controlling the fatal AML like:
- Loss of appetite
- Dysgeusia, an altered, often metallic, taste in the mouth
- A decrease in bodily minerals including calcium, potassium, and phosphorus
- Increased bilirubin levels
Some of the other side effects are a little more worrying such as:
- Noninfectious leukocytosis
- Pulmonary edema
- Acute respiratory distress syndrome (ARDS)
- Cytokine release syndrome
- Tumor lysis syndrome
Some of these, like noninfectious leukocytosis, are merely worrying while others like ARDS or tumor lysis syndrome can be severely damaging if not fatal. Even still, these symptoms are often rare, occurring in less than 10% of patients and can be taken care of with immediate treatment. According to the FDA, there is a more common side effect with equally dire consequences.
Idhifa Side Effects: Differentiation Syndrome
Differentiation syndrome is a complication of Enasidenib that occurs in 14% of patients and can be fatal. Differentiation syndrome has been observed to happen in a window that spans from 10 days after beginning Enasidenib to 5 months after. Differentiation syndrome has a variety of symptoms that include:
- Shortness of breath
- Swelling of the limbs, neck, underarms, or groin
- Rapid weight gain over 10 pounds in a week
- Bone pain
- Lightheadedness or dizziness
The real danger of differentiation syndrome, however, is that it’s often accompanied by hyperleukocytosis or an extremely high level of white blood cells. Differentiation syndrome needs to be treated quickly, or it will open up the door to a chain reaction of immune disorders that will further compound the issues already present in patients with AML, causing survivability to plummet. For this reason, the FDA has pleaded with clinicians to raise their awareness about the severity of differentiation syndrome and other complications of AML.
Who is at Risk for AML?
By analyzing patients with AML, there is a specific trend in those who contract this devastating disease.
- AML is most common in adults 65 and older, with the risk increasing with age.
- Men have been shown to have a higher risk of developing AML than are women.
- Patients who have already had to undergo chemotherapy or radiation therapy also have a higher risk.
- People exposed to extreme levels of radiation through circumstance or job hazard.
- Exposure to certain carcinogens such as benzene is shown to increase the risk.
- AML is linked to cigarette smoke, which contains benzene and other known common carcinogens.
- People who have had a previous blood disorder including myelodysplasia, myelofibrosis, polycythemia vera or thrombocythemia.
- Certain genetic disorders, such as Down syndrome, Fanconi’s anemia, Shwachman syndrome, and Diamond-Blackfan syndrome are associated with AML.
While these risk factors apply to many patients, however, many people with AML have no risk factors, and not everyone who displays these risk factors develops the AML. Additionally, Enasidenib is prescribed primarily to patients with the IDH2 mutation, so patients without this mutation are unlikely to be prescribed Enasidenib and therefore avoid the risk of complications from the treatment.
FDA Actions on Idhifa Side Effects
On August 1, 2017, the FDA approved Enasidenib to treat adult patients with a specific kind of AML known as relapsed or refractory AML with the IDH2 mutation as detected by an FDA-approved test. For over a year there were no formal disclosures by the FDA regarding Enasidenib until the final days of November 2018.
In a safety announcement from the 29th of November, the FDA warned that differentiation syndrome was not being recognized in patients even though there was a warning concerning differentiation syndrome on the boxes and in the patient medication guide.
The FDA also restated in their announcement that differentiation syndrome occurred in 14% of patients taking Enasidenb and it was a valid and dangerous threat to patient safety.
Though they did not cite any specific fatalities, the FDA did explicitly warn that “serious illness and death” were possible if differentiation syndrome were mismanaged. The FDA also called on not just practitioners, but consumers to be vigilant in watching for the warning signs of differentiation syndrome.
Idhifa Side Effect Lawsuits
Differentiation syndrome is a serious concern to patients medically, but more dangerous than that is the medical negligence that allows differentiation syndrome to develop unchecked. In addition to being vigilant, consumers should know their rights if they are not treated with the urgency necessary to prevent serious injury.
If you or a loved one have suffered from differentiation syndrome or any other complication arising from treatment including Enasidenib, legal recourse may be available to you.
Parker Waichman, LLP. is accepting cases of those disenfranchised by careless actions of clinicians who fail to inform or examine patients for complications of Enasidenib properly.