SAN DIEGO – All-trans retinoic acid (ATRA) plus arsenic trioxide with or without chemotherapy induces high remission rates among patients with acute promyelocytic leukemia (APL), according to a study presented at the American Society of Hematology (ASH) 58th Annual Meeting and Exposition.1
For the multicenter, open-label, phase 4 APL 2012 trial, researchers enrolled 794 patients with APL. All participants received ATRA and arsenic trioxide as induction therapy in combination with doxorubicin anthracycline for patients at high risk and those at intermediate risk until the white blood cell count was greater than 10 x 109/L.
During consolidation, patients with low-risk APL were randomly assigned to receive either 2 cycles of ATRA plus arsenic trioxide or 2 cycles of ATRA plus chemotherapy. Patients of intermediate-risk disease received either 3 cycles of ATRA plus arsenic trioxide or 2 cycles of ATRA plus chemotherapy. Patients of high-risk disease were given 2 cycles of ATRA plus arsenic trioxide and an anthracycline in addition to 1 cycle of ATRA plus arsenic trioxide, or 2 cycles of ATRA plus an anthracycline with cytarabine and 1 cycle of ATRA plus intermediate-dose cytarabine.
Patients of low- and intermediate-risk APL who achieved molecular remission then received 3 cycles of maintenance therapy with ATRA and arsenic trioxide, while those with high-risk disease received 5 cycles of ATRA, arsenic trioxide, and methotrexate.
Results showed that 97.1% of patients achieved complete remission, with early death occurring in 2.9% and relapse in 19 patients.
“ATRA plus arsenic trioxide and chemotherapy was associated with high complete remission rate and reduced early death,” said principal investigator Junmin Li, department of hematology, Rui Jin Hospital, Shanghai, China.
Among patients with low-risk APL, the 3-year estimated disease-free survival rate was 100% with ATRA plus arsenic trioxide vs 94.1% with ATRA plus chemotherapy. In patients with intermediate-risk disease, 3-year estimated disease-free survival rate was 96.9% with ATRA and arsenic trioxide compared 97.9% with ATRA plus chemotherapy, and in those with high-risk disease, it was 92.4% with doxorubicin and 93.7% with cytarabine, respectively.
“For patients with low-risk APL, ATRA plus arsenic trioxide was not inferior to ATRA plus chemotherapy,” said Dr Li. “For intermediate-risk APL, arsenic trioxide replaced chemotherapy in post-remission therapy, and for high-risk APL, arsenic trioxide reduced chemotherapy by replacing cytarabine.”
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The 3-year overall survival for patients with low-, intermediate-, and high-risk APL was 98.6%, 96.2%, and 90.8%, respectively, with survival being significantly prolonged for patients with low-to-intermediate risk compared with those with high-risk disease.
- Li J, Chen L, Zhu H, et al. Retinoic acid and arsenic trioxide with or without chemotherapy for acute promyelocytie leukemia with different risk stratifications: A interim analysis of China APL 2012 study. Paper presented at: American Society of Hematology (ASH) 58th Annual Meeting and Exposition; December 3-6, 2016; San Diego, CA.