Venetoclax as cytoreductive therapy in high-risk acute promyelocytic leukemia: A potential alternative to anthracyclines.

6521 Background: High-risk acute promyelocytic leukemia (APL) presents a significant mortality risk during induction therapy, primarily due to complications like disseminated intravascular coagulation (DIC) and treatment-related toxicities. Anthracyclines, traditionally used for cytoreduction, can cause cardiotoxicity, increase DIC risk, and induce severe neutropenia. Venetoclax has demonstrated efficacy in relapsed/refractory APL. This study explored the feasibility of using venetoclax for cytoreduction in high-risk APL patients, particularly those contraindicated for anthracyclines (cardiac issues, advanced age and in select patients based on physician discretion). Methods: We evaluated the safety and efficacy of venetoclax in high-risk APL patients unsuitable for anthracycline-based induction therapy. Venetoclax was initiated at 100 mg and gradually increased to 400 mg over a week. Treatment duration was determined by the patient's leukocyte count, with the goal of achieving a count below 4000/mm³. All patients received standard ATRA (All-Trans Retinoic Acid) + ATO (Arsenic Trioxide) induction. Results: Ten patients received venetoclax for cytoreduction. The median age was 45 years (range: 26-70). The median duration of venetoclax therapy was 8 days (range:6-12). All patients achieved complete hematological remission within 31 days of induction and molecular remission by 28 days of the first consolidation cycle. Two patients experienced laboratory tumor lysis syndrome, and one developed differentiation syndrome which was effectively managed with continued venetoclax therapy. No patients required interruption of ATRA or ATO. Notably, no patients experienced prolonged neutropenia (&gt; 28 days), severe mucositis (Grade 3 or 4), cardiotoxicity, or DIC. Conclusions: This study demonstrates the feasibility of using venetoclax for cytoreduction in high-risk APL patients. Venetoclax effectively reduced tumor burden while minimizing the risks associated with anthracyclines. These encouraging results warrant further investigation into the potential role of venetoclax in high-risk APL to improve patient outcomes and mitigate treatment-related toxicities. Patient characteristics. Patient Age/Sex WBC(10^3/µL) Platelet(10^3/µL) Hb (g/L) BM blast (%) WBC max (10^3/µL) No of days venetoclax used Cardiac comorbidity Time to achieve HCR (days) 45/M 15000 30000 9 30 25000 9 CAD 26 40/F 13000 25000 8.8 55 19000 7 NIL 24 33/M 12000 35000 8.1 45 18000 7 NIL 28 31/F 25000 45000 9.6 40 25000 9 NIL 30 65/M 17000 10000 7.5 33 19000 9 NIL 30 45/F 15000 10000 8.5 25 16000 8 RHD 28 66/M 22000 20000 9.7 60 24000 7 CAD 29 70/F 38000 25000 7.8 34 45000 10 CAD 31 46/M 16000 10000 7 33 18000 8 <ja