Faculty, Staff and Student Publications

Language

English

Publication Date

8-1-2025

Journal

American Journal of Hematology

DOI

10.1002/ajh.27723

PMID

40401707

PMCID

PMC12510378

PubMedCentral® Posted Date

10-10-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Outcomes in patients with relapsed/refractory (RR) AML are poor. We sought to investigate if CPX-531 in combination with venetoclax (CPX + VEN) was tolerable and effective in RR AML. This was a single institution phase 1b/2 trial of CPX + VEN. Patients aged ≥ 18 years with RR AML who were fit for intensive chemotherapy were eligible. Prior venetoclax exposure was allowed. The phase 1b portion followed a 3 + 3 design to identify the recommended phase 2 dose (RP2D) for the expansion cohort. At the starting dose level of −1, prolonged myelosuppression was observed, leading to dose level −2 (CPX-351 dosed at daunorubicin 44 mg/m2 on days 1,3, and 5 and venetoclax 300 mg days 2–8) being chosen as the RP2D. Thirty three patients with a median age of 58 years (range, 26–72) were treated. Patients were heavily pretreated, with 58% with prior venetoclax exposure, 44% in the second salvage or later, and 30% with prior stem cell transplant (SCT). Adverse cytogenetics were present in 51% of patients, with myelodysplasia-related mutations in 64%, and TP53mut in 21%. The overall response rate (ORR) was 46% (95% CI, 30–62), with a composite CR rate (CRc) of 39% (95% CI, 25–56). Patients in first salvage with wildtype TP53 had a CRc rate of 70% (95% CI, 40–89), with undetectable MRD in 71% (95% CI, 36–92) and a 2-year OS of 49% (95% CI, 23–100). Eleven (73%) responding patients underwent SCT. The 30-day mortality was 9%, with a 60-day mortality of 21%. The most common adverse events were related to myelosuppression. CPX + VEN has activity in RR AML, particularly when used in first salvage and in patients who do not harbor TP53 mutations.

Keywords

Humans, Middle Aged, Leukemia, Myeloid, Acute, Sulfonamides, Aged, Bridged Bicyclo Compounds, Heterocyclic, Female, Male, Adult, Antineoplastic Combined Chemotherapy Protocols, Daunorubicin, Recurrence, Cytarabine, AML, CPX-VEN, clinical trial

Published Open-Access

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