Differentiation syndrome in patients of IDH-mutated acute myeloid leukemia treated with ivosidenib and enasidenib

The study evaluated the occurrence of differentiation syndrome (DS) in patients with IDH-mutated acute myeloid leukemia (AML) under ivosidenib (Tibsovo) and enasidenib (Idhifa) therapy. The authors found that DS is a common and adverse condition in such patients.

Mutations or changes in the isocitrate dehydrogenase (IDH) gene can cause AML. IDH-inhibitors like ivosidenib (IVO) and enasidenib (ENA) deactivate mutated IDH. They can treat patients with IDH-mutated relapsed/refractory (r/r) AML. DS causes shortness of breath, fever, and kidney failure. DS in patients with r/r AML under IVO/ENA has not been systematically analyzed so far.

Researchers from the Food and Drug Administration (FDA) analyzed data from clinical trials with IVO and ENA. Among patients with IDH-mutated r/r AML, 179 received IVO, and 214 received ENA. Medical reports within the first 90 days of therapy were assessed for DS.

Computer algorithm estimated potential DS in 72 (40%) patients on IVO and 86 (40%) on ENA. The authors found that 19% of the IVO group and 19% of the ENA group were actually DS.

Patients with 48% or more leukemic white blood cells in the bone marrow had higher risks of DS. Patients with high DS risks also had 25% or more young leukemia white blood cells in the blood for IVO and 15% or more for ENA.

Overall, two-thirds of the DS cases were severe. An increase in white blood cells occurred as side effects of IVO (79%) and ENA (61%) in patients with DS. Overall, patients with DS received higher doses of IVO or ENA compared to those without DS. DS occurred after 20 days of IVO and 19 days of ENA therapy, on average.

Complete remission (CR) signifies a lack of cancer symptoms. CRh refers to CR with partial recovery of blood cells. CR and CRh occurred less frequently in patients with DS (18% vs 36% with vs without IVO and 18% vs 25% with vs without ENA). 

The study concluded that DS is a common and harmful side effect of IDH inhibitors in patients with r/r AML. The authors suggest that following some quality diagnostic standards may detect DS early. This can reduce complications and deaths.

This study used medical records data. Some information might have been missing. This may have affected the results.