ASH Clinical News ACN_5.3_web | Page 10

IDHIFA® (enasidenib) is indicated for the treatment of adult patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation as detected by an FDA-approved test. FOR PATIENTS WITH R/R AML AND AN IDH2 MUTATION MYELOID DIFFERENTIATION OPENS UP THE POSSIBILITIES IDHIFA: The first and only oral, targeted inhibitor of IDH2 23 % Rate of complete response (CR)* or CR with partial hematologic recovery (CRh)† 8.2 mo Median duration of CR/CRh ‡ n=46/199 (95% CI, 4.3-19.4) n=46/199 (95% CI, 18%-30%) 34 % Rate of conversion from transfusion dependence to transfusion independence (RBC and platelet) n=53/157 IDHIFA was studied in an open-label, single-arm, multicenter, clinical trial of patients with R/R AML and an IDH2 mutation who were assigned a starting dose of 100 mg daily until disease progression or unacceptable toxicity. Dose reductions were allowed to manage adverse events. Patients’ IDH2 mutations were either prospectively identified or retrospectively confirmed by the Abbott RealTime™ IDH2 assay. § Patients were a median of 68 years old and had a median of 2 prior therapies. Efficacy was established on the basis of the rate of CR/CRh, the duration of CR/CRh, and the rate of conversion from transfusion dependence to transfusion independence. || The median follow-up was 6.6 months (range, 0.4 to 27.7). * CR was defined as <5% of blasts in the bone marrow, no evidence of disease, and full recovery of peripheral blood counts (platelets >100,000/μL and ANC >1,000/μL). CRh was defined as <5% of blasts in the bone marrow, no evidence of disease, and partial recovery of peripheral blood counts (platelets >50,000/μL and ANC >500/μL). ‡ Duration of CR/CRh was defined as time since first response of CR or CRh to relapse or death, whichever is earlier. § Abbott RealTime™ IDH2 assay is the FDA-approved test for selection of patients with AML for treatment with IDHIFA. || Patients were defined as transfusion independent if they received no RBC or platelet transfusions within any 56-day post-baseline period. ANC, absolute neutrophil counts; CI, confidence interval; RBC, red blood cell; R/R, relapsed/refractory. † IMPORTANT SAFETY INFORMATION WARNING: DIFFERENTIATION SYNDROME Patients treated with IDHIFA have experienced symptoms of differentiation syndrome, which can be fatal if not treated. Symptoms may include fever, dyspnea, acute respiratory distress, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, lymphadenopathy, bone pain, and hepatic, renal, or multi-organ dysfunction. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution. WARNINGS AND PRECAUTIONS Differentiation Syndrome: See Boxed WARNING. In the clinical trial, 14% of patients treated with IDHIFA experienced differentiation syndrome, which may be life-threatening or fatal if not treated. Differentiation syndrome has been observed with and without concomitant hyperleukocytosis, as early as 10 days and at up to 5 months after IDHIFA initiation. Symptoms in patients treated with IDHIFA included acute respiratory distress represented by dyspnea and/or hypoxia and need for supplemental oxygen; pulmonary infiltrates and pleural effusion; renal impairment; fever; lymphadenopathy; bone pain; peripheral edema with rapid weight gain; and pericardial effusion. Hepatic, renal, and multi-organ dysfunction have also been observed. If differentiation syndrome is suspected, initiate systemic corticosteroids and hemodynamic monitoring until improvement. Taper corticosteroids only after resolution of symptoms. Differentiation syndrome symptoms may recur with premature discontinuation of corticosteroids. If severe pulmonary symptoms requiring intubation or ventilator support and/or renal dysfunction persist for more than 48 hours after initiation of corticosteroids, interrupt IDHIFA until signs and symptoms are no longer severe. Hospitalization for close observation and monitoring of patients with pulmonary and/or renal manifestation is recommended. Embryo-Fetal Toxicity: Based on animal embryo-fetal toxicity studies, IDHIFA can cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with IDHIFA and for at least 1 month after the last dose. Pregnant women, patients becoming pregnant while