By Kerri Fitzgerald
A study assessed CPX-531 plus venetoclax in patients with relapsed or refractory acute myeloid leukemia (AML) and found that the combination was particularly effective in first salvage therapy and in patients without TP53 mutation.
Tapan M. Kadia, MD, of The University of Texas MD Anderson Cancer Center, and colleagues published the results in the American Journal of Hematology.
The single-institution, phase 1b/2 study included 33 adult patients (median age, 58 years) who were fit for intensive chemotherapy. The phase 1b trial utilized a 3+3 design to identify the recommended phase 2 dose, which was determined to be CPX-351 dosed at daunorubicin 44 mg/m2 on days 1, 3, and 5 and venetoclax 300 mg on days 2 through 8.
Patients were heavily pretreated:
- 58% received prior venetoclax
- 44% were in second salvage therapy or later
- 30% had underwent hematopoietic cell transplant (HCT)
About half (51%) of patients had adverse cytogenetics, including 64% with myelodysplasia-related mutations and 21% with TP53 mutation.
The overall response rate was 46% (95% CI, 30-62), with a composite complete remission (CRc) rate of 39% (95% CI, 25-56). Patients in first salvage with wild-type TP53 had a CRc rate of 70% (95% CI, 40-89). In this cohort, 71% had undetectable measurable residual disease, and the 2-year overall survival rate was 49%.
Eleven patients (73%) who responded to treatment then underwent HCT. The 30- and 60-day mortality rate was 9%, and 21%, respectively. The most common adverse events were related to myelosuppression.
The study was supported by Jazz Pharmaceuticals.
Reference
Kadia TM, Jen WY, Bataller A, et al. A phase 2 trial of CPX-351 combined with venetoclax in relapsed or refractory acute myeloid leukemia. Am J Hematol. 2025;100(8):1365-1373. doi:10.1002/ajh.27723
