Long-term outcome of acute promyelocytic leukemia treated with all- trans-retinoic acid, arsenic trioxide, and gemtuzumab

Abstract

The combination of all-trans-retinoic acid (ATRA) plus arsenic trioxide (ATO) has been shown to be superior to ATRA plus chemotherapy in the treatment of standard-risk patients with newly diagnosed acute promyelocytic leukemia (APL). A recent study demonstrated the efficacy of this regimen with added gemtuzumab ozogamicin (GO) in high-risk patients. We examined the long-term outcome of patients with newly diagnosed APL treated at our institution on 3 consecutive prospective clinical trials, using the combination of ATRA and ATO, with or without GO. For induction, all patients received ATRA (45 mg/m2 daily) and ATO (0.15 mg/kg daily) with a dose of GO (9 mg/m2 on day 1) added to high-risk patients (white blood cell count, >10 × 109/L), as well as low-risk patients who experienced leukocytosis during induction. Once in complete remission, patients received 4 cycles of ATRA plus ATO consolidation. One hundred eighty-seven patients, including 54 with high-risk and 133 with low-risk disease, have been treated. The complete remission rate was 96% (52 of 54 in high-risk and 127 of 133 in low-risk patients). Induction mortality was 4%, with only 7 relapses. Among low-risk patients, 60 patients (45%) required either GO or idarubicin for leukocytosis. Median duration of follow-up was 47.6 months. The 5-year event-free, disease-free, and overall survival rates are 85%, 96%, and 88%, respectively. Late hematological relapses beyond 1 year occurred in 3 patients. Fourteen deaths occurred beyond 1 year; 12 were related to other causes. This study confirms the durability of responses with this regimen.

© 2017 by The American Society of Hematology.

Figures

Figure 1.

Treatment regimen. (A) Details of induction course, regimen A. (B) Details of induction course, regimen B. *One dose of GO 9 mg/m2 was given on day 1 for high-risk patients (defined by WBC count >10 × 109/L on presentation) and low-risk patients in whom the WBC count increased to more than 10 × 109/L during the first 4 weeks of therapy. D, day; mCR, marrow complete remission; wks, weeks.

Figure 2.

Patient disposition.

Figure 3.

Survival outcomes for the whole population. (A) Event-free survival. (B) Disease-free survival. (C) Overall survival for the entire group.

Figure 4.

Outcomes by risk subsets. (A) Event-free survival by risk group. (B) Disease-free survival by risk group. (C) Overall survival by risk group.

Figure 5.

Outcomes by age. (A) Event-free survival by age group. (B) Disease-free survival by age group. (C) Overall survival by age group.

Figure 6.

Survival for specified subsets. (A) Gemtuzumab vs idarubicin among high-risk APL patients. (B) Overall survival by cytogenetics.