Clinical outcomes and rates of molecular remission with all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3) combination therapy in newly diagnosed acute promyelocytic leukemia (APL)
6503 Background: ATRA and anthracyclines provide durable remissions in patients with untreated APL. As2O 3 has improved outcomes in untreated and relapsed/refractory APL. The aim of this study was to determine the rates of complete response (CR) and molecular remission with ATRA and As2O 3 combination therapy in untreated APL. Methods: From 2/02 to 1/06, 53 patients with untreated APL received ATRA 45 mg/m2 daily and As2O 3 0.15 mg/kg IV 1-hr infusion daily starting on day 10. Patients with WBC>10×109/L also received gemtuzumab ozogamicin (GO) 9 mg/m2 on day 1 and/or idarubicin 12 mg/m2 on days 1–4. Patients in CR received As2O 3 0.15 mg/kg IV on days 1–5 weekly for 4 weeks on and 4 weeks off and ATRA 45 mg/m2 daily for 2 weeks on and 2 weeks off (for 28 weeks). Polymerase chain reaction (PCR) testing for PML-RARα (sensitivity level, 10−4) was performed every 3 months from CR for 2 years. Patients with molecular relapse received GO 9 mg/m2 once monthly for 3 months in addition to ATRA and As2O 3 as in postremission therapy. If PCR became negative, only the single dose of GO was given. Results: The median age was 46 years; and 20% of patients were Sanz low risk, 40% intermediate, and 40% high risk. The CR rate was 91% (low risk 91%, intermediate 95%, high risk 86%). The median follow-up in surviving patients was 1.6 years. Six patients died during induction, and 2 died in CR from other cancers. The 1-yr survival rate was 88%. Three patients relapsed (at 9, 9, and 16 months). The 1-yr failure-free survival (FFS) rate in responding patients was 94% (high risk 86%, other risk 100%). Molecular remission rates are shown in the Table . Grade 3–4 nonhematologic toxicities were infections (n=16), neurologic (n=4), cardiac arrhythmias (n=4), APL differentiation syndrome (n=4), and headache (n=2). Conclusions: ATRA plus As2O 3 results in high rates of CR, molecular remission, FFS, and survival and is an alternative to ATRA and idarubicin combination therapy in low-risk APL. [Table: see text] No significant financial relationships to disclose.