Aclarubicin Hydrochloride

Venetoclax (VEN), a BCL-2 inhibitor, was approved in Japan in March 2021, for acute myeloid leukemia (AML). We retrospectively analyzed the impact of VEN approval on treatment patterns and outcomes in older AML patients aged 65–74 years unfit for intensive chemotherapy in Japan. Using the Hokkaido Leukemia Net database, we categorized 101 patients into pre-VEN ( n  = 46) and post-VEN ( n  = 55) cohorts, excluding those who had acute promyelocytic leukemia or received intensive chemotherapy. Following VEN approval, VEN + azacitidine (AZA) became the most frequently used initial regimen (56%). Despite higher rates of TP53 mutations and complex karyotypes (35.5%), VEN + AZA achieved comparable response rates (CR + CRi: 64.5%) and overall survival (OS, median 11.7 months) to r7 + 3 (CR + CRi: 64.5%, median OS: 13.1 months), and superior outcomes to cytarabine + aclarubicin + G-CSF (CAG, CR + CRi 37.5%, median OS 6.8 months) or AZA monotherapy (CR + CRi 12.5%, median OS 4.5 months). Early mortality at 60 days from diagnosis was lower with VEN + AZA (3.2%) than with reduced-dose cytarabine plus anthracycline (r7 + 3) (12.9%), CAG (26.7%), or AZA monotherapy (18.8%). Our findings demonstrate a substantial shift in real-world treatment practices following VEN approval and suggest that VEN + AZA is an effective option for older AML patients with adverse genetic features.

We conducted a prospective, multicenter, Phase II study to evaluate the safety and efficacy of venetoclax/azacitidine/low‐dose cytarabine/aclarubicin/granulocyte colony‐stimulating factor (G‐CSF) (VA‐CAG) in young patients with newly diagnosed acute myeloid leukemia (ND‐AML). The VA‐CAG regimen included venetoclax (100 mg/day, Days 1–2; 200 mg, Day 3; 400 mg/day, Days 4–21), azacitidine (75 mg/m 2 , Days 1–7), cytarabine (10 mg/m 2 /12 h, Days 1–7), aclarubicin (12 mg/m 2 , Days 1, 3, 5, and 7), and G‐CSF (5 μg/kg/day, Days 0–8). The primary endpoint was the complete remission (CR) rate after Cycle 1; the secondary endpoints included measurable residual disease (MRD)‐negative remission rate, adverse events, and duration of remission (DOR). A total of 120 subjects were enrolled. The median age was 50 years (interquartile range, IQR, 36–57). The CR and composite complete response (CRc) rates were 91% (95% CI 86%–96%) and 95% (95% CI 91%–99%), respectively; 84% (95% CI 81%–88%) of the CRc patients achieved MRD‐negative remission. Common Grade ≥4 adverse events included neutropenia (96%), thrombocytopenia (86%), febrile neutropenia (24%), pneumonia (4%), and sepsis (4%). The median times to recovery of absolute neutrophil count (ANC) ≥ 0.5 × 10 9 /L and platelet count ≥ 20 × 10 9 /L for responding patients were 14 days (IQR, 9–19) and 10 days (IQR, 4–16), and the 60‐day mortality rate was 0%. With a median follow‐up of 22.1 months (95% CI 20.4–23.7 months), 34 subjects subsequently received hematopoietic stem cell transplantation (HSCT). The median DOR values of all patients and the patients who did not receive HSCT were not reached. Hence, the VA‐CAG regimen is a safe and effective first‐line induction chemotherapy for ND‐AML patients.