A Phase 2 study of CPX-351 in combination with venetoclax in patients with newly diagnosed high-risk acute myeloid leukemia

Venetoclax has been combined with intensive chemotherapy regimens in the treatment of acute myeloid leukemia (AML). We aimed to investigate the safety and efficacy of venetoclax combined with full-dose CPX-351 (CPX + VEN) in newly diagnosed (ND) AML. Seventeen patients with a median age of 59 years (range, 43-69) were treated; 71% had secondary AML, 47% had prior hypomethylating agent (HMA) exposure, 59% had myelodysplastic syndrome (MDS)-related (MR) mutations, 47% had complex karyotype, and 29% were TP53 mutated. The overall response rate (ORR) was 82% (95% CI, 57-96) with a composite complete remission rate (CRc) of 71% (95% CI, 50-93). Patients with MR mutations had an ORR of 100% (95% CI, 69-100), including a CRc of 90% (95% CI, 55-100). Patients with prior HMA exposure had a CRc of 63% (95% CI, 24-91). With a median follow-up time of 11.8 months, the median overall survival (OS) was 12.8 months (95% CI, 5-NE) with a 2-year OS of 34% (95% CI, 10-61). Patients with MR mutations had a median OS of 17.9 months versus 5.1 months in patients without MR mutations (P = 0.039). Twelve (86%) of 14 responding patients proceeded to stem cell transplant (SCT); the median recurrence-free survival and OS landmarked from date of SCT were 14.7 months (95% CI, 1-32) and 14.7 months (95% CI, 4-25), respectively. The 4-week mortality was 0% and the 8-week mortality was 17%. The most common adverse events were related to myelosuppression. CPX + VEN resulted in high remission rates and enabled progression to allogenic SCT for the majority of a highly adverse group of ND AML patients.