Venetoclax and CPX-531 Demonstrates Promising Activity Among Patients With Relapsed/Refractory Acute Myeloid Leukemia

Venetoclax in combination with CPX-531, a liposomal encapsulation of cytarabine and daunorubicin, for the treatment of relapsed/refractory (R/R) acute myeloid leukemia (AML), especially among patients in first salvage and who do not have TP53 mutations, demonstrate promising clinical activity, according to phase 2 study results published in American Journal of Hematology. 

Researchers conducted a phase 1b/2 trial evaluating the safety and efficacy of CPX-531 combined with venetoclax among patients with R/R AML who had previously received treatment, including prior venetoclax therapy. 

Overall, 33 patients with R/R AML were included, of which the median age was 58 years (range, 26 to 72). Most patients were heavily pretreated, including prior venetoclax therapy (58%), second salvage or later (44%), and stem cell transplant (30%). Mutations present at analysis included myelodysplasia-related mutations (64%) and TP53 mutations (21%).  

Among treated patients, the overall response rate (ORR) was 46% (95% confidence interval [CI], 30 to 62). The composite complete remission (CRc) rate was 39% (95% CI, 25 to 56). 

Patients who were in first salvage therapy and had wildtype TP53 had a CRc rate of 70% (95% CI, 40 to 89). Additionally, undetectable MRD was achieved by 71% of patients and the OS at 2 years was 49% (95% CI, 23 to 100). The 30-day mortality was 9%, which increased to 21% at 60 days. Stem cell transplantation was undergone by 73% of patients following treatment with CPX-531 and venetoclax. 

In terms of safety, the most common adverse event was myelosuppression. 

“[CPX-531 plus venetoclax] has activity in RR AML, particularly when used in first salvage and in patients who do not harbor TP53 mutations,” the researchers concluded.

Source:

Kadia TM, Jen W, Bataller A, et al. A Phase 2 Trial of CPX‐351 Combined With Venetoclax in Relapsed or Refractory Acute Myeloid Leukemia. American Journal of Hematology. Published online May 22, 2025. doi:10.1002/ajh.27723