Efficacy and Safety of Venetoclax Added to Arsenics Plus All-Trans-Retinoic Acid Combination Salvage Regimen for Patients with Relapsed/Refractory Acute Promyelocytic Leukemia

Background: Despite high cure rates in acute promyelocytic leukemia (APL), treatment outcomes in patients with relapsed/refractory (R/R) APL, particular with central nervous system (CNS) involvement relapse remains challenge. Recently, venetoclax (VEN, a selective BCL2 inhibitor) plus azacitidine has shown superior efficacy to azacitidine monotherapy in newly diagnosed unfit patients. However, data of venetoclax in APL patients were Limited. Here, we aim to analysis the efficacy and safety of VEN plus arsenics (arsenic trioxide or oral arsenic drug, realgar-indigo naturalis formula) plus ATRA based salvaged regimen in R/R APL from our center. Patients and methods: We retrospectively analyzed cases with R/R APL who received VEN plus arsenics and ATRA based regimen at our institution from July 2021 to December 2023. During the reinduction cycle, patients received 0.15 mg/kg/day intravenous infusion of Arsenic trioxide or oral RIF daily 60 mg/kg/day. ATRA was administered 25 mg/m2/day. VEN was administered using a daily ramp-up strategy (100 mg on day 2, 200 mg on day 3, and 400 mg on days 4-28). The last date of follow-up for this analysis was May 2024. Results: Thirty-one patients with R/R APL were enrolled, 10 patients has co-occurred with CNS relapse, and 1 patient with CNS relapse only. Four patients had ≥ 2 therapies. All patients had prior exposure to arsenics and ATRA. The median age was 44 years (ranges, 18-72). After once cycle of reinduction, the overall response rate (complete remission/complete remission with incomplete count recovery) was 97% (30 of 31), CR was achieved in 27 patients. No early death was occurred. Side effects were manageable. With the median follow-up of 15 month, the 1-year event-free survival and overall survival rates is 78.7% and 96.7%, respectively. Conclusions: Our results showed that the combination of VEN plus arsenics and ATRA appeared to be a highly effective therapy option for patients with R/R APL, and underline its potential activity also in patients with CNS involvement.