Chidamide and CAG Plus Venetoclax-Azacitidine Regimen Demonstrates High Response Rates in Older Patients With Acute Myeloid Leukemia

The combination of chidamide with cytarabine, aclarubicin, and G‐CSF (CAG) plus venetoclax-azacitidine (CACAG-VEN) demonstrated high response rates and manageable safety in older patients with newly diagnosed acute myeloid leukemia (AML), according to results from a phase 2 trial published in Frontiers in Immunology.

Due to increased risk factors such as comorbidities and poor organ function, elderly patients with AML often respond poorly to standard induction therapies. Researchers conducted a single-arm, open-label phase 2 study evaluating the efficacy and safety of CACAG-VEN in AML patients aged over 60 years.

The primary end point was overall response (ORR) as well as composite complete response (CRc) and partial response (PR) after first administration of induction therapy regimen.

Overall, 40 previously untreated patients received induction therapy with CACAG-VEN. The median age was 64.0 years (range, 60.0 to 74.0) and were mostly male (62.5%). About 75% of patients had de novo AML and 40% were at adverse risk, about 20% of patients had an NPM1 mutation. After initial induction treatment, 67.5% received another cycle of CACAG-VEN. Following chemotherapy, 30% of patients received allogeneic hematopoietic stem cell transplantation.

After the initial cycle, the ORR was 97.5% (95% confidence interval [CI], 85.3 to 99.9), with a CRc rate of 85.0% (95% CI, 69.5 to 93.8) after 1 induction cycle. The PR rate was 12.5% (95% CI, 4.7 to 27.6).  Among patients with adverse risk, the CRc rate was 81.3% (95% CI, 54.0 to 95.0). The overall survival (OS) rate was 73.4% (95% CI, 55.9 to 84.8) at 12 months.

In terms of safety, the most common grade 3 or 4 non-hematologic adverse events were febrile neutropenia (37.5%), pneumonia (7.5%), sepsis (5.0%), and elevated bilirubin (2.5%). The 12-month overall survival rate was 73.4% (95% CI, 55.9 to 84.8%).

"The CACAG-VEN regimen was well tolerated, with no early-death within 30 days and short duration of pancytopenia,” the researchers concluded. They added, “a well designed randomized trial with long-term follow-up is now warranted.”

Source:

Liu Q, Yang J, Lv L, et al. Phase 2 study of chidamide in combination with CAG and venetoclax-azacitidine in older patients with newly diagnosed acute myeloid leukemia. Frontiers in Immunology. Published online February 25, 2025. doi: 10.3389/fimmu.2025.1525110