Differentiation syndrome associated with treatment with IDH2 inhibitor enasidenib: pooled analysis from clinical trials.

Treatment with enasidenib, a selective mutant isocitrate dehydrogenase isoform 2 (IDH2) inhibitor, has been associated with the development of differentiation syndrome (DS) in patients with acute myeloid leukemia (AML). Studies on the incidence and clinical features of DS are limited in this setting, and diagnosis is challenging because of nonspecific symptoms. This study assessed the incidence, diagnostic criteria, risk factors, and correlation with clinical response of DS based on the pooled analysis of 4 clinical trials in patients with IDH2-mutated AML treated with enasidenib as monotherapy, or in combination with azacitidine or with chemotherapy.

Crenolanib and Intensive Chemotherapy in Adults With Newly Diagnosed FLT3-Mutated AML.

Purpose: Crenolanib is a second-generation tyrosine kinase inhibitor with activity against - and -mutant AML. We conducted a trial of crenolanib plus intensive chemotherapy in adults with newly diagnosed -mutant AML.

Methods: Eligible patients were 18 years and older.

Modeling of the Tricuspid Valve and Right Ventricle in Hypoplastic Left Heart Syndrome With a Fontan Circulation.

Background: In hypoplastic left heart syndrome, tricuspid regurgitation (TR) is associated with circulatory failure and death. We hypothesized that the tricuspid valve (TV) structure of patients with hypoplastic left heart syndrome with a Fontan circulation and moderate or greater TR differs from those with mild or less TR, and that right ventricle volume is associated with TV structure and dysfunction.

Methods: TV of 100 patients with hypoplastic left heart syndrome and a Fontan circulation were modeled using transthoracic 3-dimensional echocardiograms and custom software in SlicerHeart.

Targeting RARA overexpression with tamibarotene, a potent and selective RARα agonist, is a novel approach in AML.

A superenhancer at the retinoic acid receptor alpha (RARA) gene is associated with RARA mRNA overexpression in ∼30% of non-acute promyelocytic leukemia acute myeloid leukemia (AML) and in ∼50% of myelodysplastic syndromes (MDS). RARA overexpression is an actionable target for treatment with tamibarotene, an oral potent and selective RARα agonist. Sensitivity to the RARα agonist tamibarotene was demonstrated in RARA-high but not RARA-low preclinical AML models.