ASH Clinical News October 2017 | Page 32

Written in Blood years) with low or intermediate-1 risk MDS or chronic myelomonocytic leukemia (CMML; per the International Prognostic Scoring System [IPSS]) between November 2012 and February 2016. Patients with other active and uncontrolled infection or intercurrent illnesses, or who had received any prior therapy with HMAs were excluded. Most patients (90%) had good or intermediate-risk cytogenetics. The majority of patients had MDS (n=97), including 20 (18%) with therapy-related MDS; six patients (5%) had an overlap MDS/ myeloproliferative neoplasm (MPN) other than CMML, and 16 (14%) had CMML. Using a Bayesian response-adaptive design, investigators randomized patients to receive: • decitabine 20 mg/m 2 intravenously daily for 3 days (n=73) • azacitidine 75 mg/m 2 intravenously daily for 3 days (n=40) Other notable adverse drug reactions that occurred in less than 10% of patients treated with VYXEOS during induction or consolidation included: • Ear and labyrinth disorders: Deafness, Deafness unilateral • Eye Disorders: Eye conjunctivitis, Dry eye, Eye edema, Eye swelling, Eye irritation, Eye pain, Ocular discomfort, Ocular hyperemia, Periorbital edema, Scleral hyperemia • Gastrointestinal disorders: Dyspepsia • Psychiatric disorders: Hallucinations • Respiratory, thoracic and mediastinal disorders: Pneumonitis Laboratory Abnormalities All patients developed severe neutropenia, thrombocytopenia, and anemia. See Table 3 for the incidences of Grade 3 thrombocytopenia and Grade 4 neutropenia that were prolonged in the absence of active leukemia. Table 3: Prolonged Cytopenias for Patients in Study 1 Induction 1 VYXEOS 7+3 N=58 N=34 n (%) n (%) Prolonged thrombocytopenia a Prolonged neutropenia a Consolidation 1 b VYXEOS 5+2 N=48 N=32 n (%) n (%) 16 (28) 4 (12) 12 (25) 5 (16) 10 (17) 1 (3) 5 (10) 1 (3) Platelets <50 Gi/L or neutrophils <0.5 Gi/L lasting past cycle day 42 in the absence of active leukemia. b Patients receiving at least 1 consolidation. a Grade 3-4 chemistry abnormalities occurring in greater than 5% of VYXEOS treated patients in Study 1 are presented in Table 4. Table 4: Grade 3-4 a Chemistry Abnormalities ≥5% of VYXEOS Treated Patients in Study 1 Induction VYXEOS 7+3 N=153 N=151 n (%) n (%) Chemistry Abnormalities Hyponatremia 21 (14) 20 (13) Hypokalemia 14 (9) 19 (13) Hypoalbuminemia 11 (7) 19 (13) Hyperbilirubinemia 9 (6) 6 (4) Alanine 7 (5) 8 (5) aminotransferase Consolidation VYXEOS 5+2 N=49 N=32 n (%) n (%) 3 (6) 3 (6) 1 (2) 1 (2) 0 2 (6) 4 (13) 1 (3) 0 1 (3) Graded using NCI CTCAE version 3.0. a DRUG INTERACTIONS Cardiotoxic Agents Concomitant use of cardiotoxic agents may increase the risk of cardiotoxicity. Assess cardiac function more frequently when VYXEOS is coadministered with cardiotoxic agents [see Warnings and Precautions]. Hepatotoxic Agents Concomitant use with hepatotoxic agents may impair liver function and increase the toxicity of VYXEOS. Monitor hepatic function more frequently when VYXEOS is coadministered with hepatotoxic agents. The imbalance in treatment groups was “d