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

Abstract Background 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. Methods This was a phase 2 trial of patients with newly diagnosed APL. Induction comprised ATRA 45 mg/m 2 and ATO 0.15 mg/kg daily. GO 6–9 mg/m 2 was added for high‐risk patients and for standard‐risk patients who developed leukocytosis >10 × 10 9 /L. Consolidation consisted of four courses of ATO‐ATRA, with GO for patients who had PML::RARA persistence. Results 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. Conclusions 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).