Safety
hypophosphatemia, MDS/CMML, toxicity, AML, hyperbilirubinemia, myelosuppression, deaths, acute kidney injury
HYPOPHOSPHATEMIA, ADVERSE EVENTS, AML, ADVERSE EVENT, HYPERBILIRUBINEMIA
Non-hematologic adverse events across both cohorts are shown in Table Non-hematologic adverse events observed in either cohort (AML and MDS/CMML), regardless of causalityALT, alanine aminotransferase; AST, aspartate aminotransferaseData are n (%). Any grade 1–2 adverse event occurring in ≥ 10% of patients, and all grade 3, 4 and 5 adverse events are includedAcross both cohorts, 11 patients (28%) had at least one dose reduction or interruption of one or more study drugs, 9 patients (28%) in the AML cohort and 2 patients (25%) in the MDS/CMML cohort. Overall, 5 patients (13%) had a dose reduction of azacitidine, 6 patients (15%) had a dose reduction of venetoclax, and no patients had a dose reduction of pevonedistat. The most common reason for dose reduction of azacitidine or venetoclax was myelosuppression (accounting for 82% of dose reductions). One patient (3%) had a dose interruption of azacitidine, no patients had a dose interruption of venetoclax, and 5 patients (13%) had a dose interruption of pevonedistat. The most common reasons for dose interruptions of pevonedistat were transient hypophosphatemia (in 3 cases) and elevated transaminases (in 2 cases). One patient discontinued therapy due to treatment-related toxicity (transaminase elevation, hyperbilirubinemia and acute kidney injury, possibly related to pevonedistat).There were 7 on-study deaths (6 in the AML cohort and 1 in the MDS/CMML cohort). In the AML cohort, the 30-day and 60-day mortality rates were 6% and 16%, respectively. In the MDS/CMML cohort, the 30-day and 60-day mortality rates were 0% and 13%, respectively.