The Food and Drug Administration (FDA) is alerting health care providers about the need for early recognition and management of differentiation syndrome, a potentially lethal condition affecting patients who receive enasidenib (Idhifa). The drug was approved in 2017 for the treatment of a specific, genetically mutated form of acute myeloid leukemia. Until enasidenib's approval, differentiation syndrome had only been associated with induction chemotherapy in patients with acute promyelocytic leukemia. Health care workers may not recognize the signs and symptoms of this disorder, thereby delaying its treatment. Another recently approved drug for acute myeloid leukemia with a specific gene mutation, ivosidenib (Tibsovo), also carries a risk of this adverse effect.
Enasidenib's labeling has always carried a black box warning about the risk of differentiation syndrome, which is associated with a rapid proliferation and differentiation of myeloid cells. Information about differentiation syndrome is also available in the medication guide that comes with each prescription. However, the FDA has become aware of cases of differentiation syndrome not being recognized and of patients not receiving the proper treatment. The agency received reports of five deaths from differentiation syndrome between May 1 and July 31, 2018, in patients taking enasidenib. In clinical trials of enasidenib, 14% of patients experienced differentiation syndrome as early as 10 days and up to five months after starting treatment with the drug. In a recent systematic analysis, the FDA found that differentiation syndrome has an incidence of 19% in patients taking enasidenib, of which 5% of cases are fatal. Hyperleukocytosis may or may not be present in cases of differentiation syndrome.
Signs and symptoms of differentiation syndrome include
* fever.
* cough, shortness of breath, acute respiratory distress represented by dyspnea and/or hypoxia, and a need for supplemental oxygen.
* pulmonary infiltrates and pleural effusion.
* lymphadenopathy.
* bone pain.
* dizziness/lightheadedness.
* peripheral edema with rapid weight gain of more than 10 lbs. within a week.
* pericardial effusion.
* hepatic, renal, and multiorgan dysfunction.
The initial presentation of differentiation syndrome may be similar to that of cardiogenic pulmonary edema, pneumonia, or sepsis, further complicating recognition and treatment of the condition.
If patients develop unexplained respiratory distress or any of the symptoms listed above, differentiation syndrome should be considered. Initial treatment with oral or intravenous corticosteroids should be started as soon as possible. Hemodynamic monitoring is recommended. Intubation or ventilator support may be needed in some patients.
In addition to monitoring patients for differentiation syndrome, nurses play a key role in educating patients on the importance of reading and understanding the medication guide included with each filled prescription. Nurses should teach patients to be alert for early signs of differentiation syndrome and to seek help immediately if these develop. To read the FDA Drug Safety Communication, go to http://www.fda.gov/Drugs/DrugSafety/ucm626923.htm.