Long-term follow-up of a phase 2 study of all-trans retinoic acid, arsenic trioxide, and gemtuzumab ozogamicin in acute promyelocytic leukemia.

All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) combinations have produced excellent outcomes in patients with standard-risk acute promyelocytic leukemia (APL). Herein, the authors update their long-term results with the regimen of ATO-ATRA and gemtuzumab ozogamicin (GO) in standard-risk and high-risk APL. This was a phase 2 trial of patients with newly diagnosed APL. Induction comprised ATRA 45 mg/m2 and ATO 0.15 mg/kg daily. GO 6-9 mg/m2 was added for high-risk patients and for standard-risk patients who developed leukocytosis >10 × 109/L. Consolidation consisted of four courses of ATO-ATRA, with GO for patients who had PML::RARA persistence. One hundred forty-six patients (median age, 53.0 years; range, 19.3-83.9 years) were treated, including 106 patients (72.6%) with standard-risk APL and 40 (27.4%) with high-risk APL. GO was administered to 68 standard-risk patients (64.2%) for leukocytosis. The complete remission rate was 93.8% (95% confidence interval [CI], 92.2%-98.5%). Negative measurable residual disease status was achieved in 97.1% of patients who attained complete remission. At a median follow-up of 61.8 months (95% CI, 4.7-128.4 months), the 5-year event-free survival, disease-free survival, and overall survival rates were 92.4% (95% CI, 87.9%-97.1%), 93.6% (95% CI, 89.5%-97.8%), and 93.1% (95% CI, 88.9%-97.7%), respectively. Induction mortality was 2.7%. The most common severe adverse events were elevated transaminases in 41.0% of patients and infection in 13.7%. There were no cases of veno-occlusive disease. The combination of ATO-ATRA and GO was curative in 94% of patients who had APL with a favorable safety profile (ClinicalTrials.gov identifier NCT01409161).