Journal Article

Tamibarotene maintenance improved relapse-free survival of acute promyelocytic leukemia: a final result of prospective, randomized, JALSG-APL204 study

Usui, Noriko, Kobayashi, Yukio, Furumaki, Hiroaki, Yanada, Masamitsu, Nakagawa, Masaru, Kiyoi, Hitoshi, Ohtake, Shigeki, Takeshita, Akihiro, Atsuta, Yoshiko, Dobashi, Nobuaki, Ueda, Yasunori, Fujita, Hiroyuki, Sawa, Masashi, Tamaki, Shigehisa, Matsumura, Itaru, Sakura, Toru, Miyazaki, Yasushi, Obata, Yukako, Taniguchi, Yasuhiro, Hagihara, Maki, Naoe, Tomoki, Asou, Norio, Suzuki, Rikio, Maeda, Yoshinobu, Fujimaki, Katsumichi

2019

Overview

Between April 2004 and December 2010, we conducted a prospective randomized controlled study comparing tamibarotene with all- trans retinoic acid (ATRA) in the maintenance therapy of newly diagnosed acute promyelocytic leukemia (APL), and here report the final results of this study with a median follow-up of 7.3 years. Of 344 eligible patients who had received ATRA and chemotherapy, 319 (93%) achieved complete remission (CR). After completion of three courses of consolidation chemotherapy, 269 patients in molecular remission underwent maintenance randomization, 135 to ATRA (45 mg/m 2 daily), and 134 to tamibarotene (6 mg/m 2 daily) for 14 days every 3 months for 2 years. The primary endpoint was relapse-free survival (RFS). The 7-year RFS was 84% in the ATRA arm and 93% in the tamibarotene arm ( p  = 0.027, HR = 0.44, 95% CI, 0.21 to 0.93). The difference was prominent in high-risk patients with initial leukocytes ≥ 10.0 × 10 9 /L (62% vs. 89%; p  = 0.034). Tamibarotene was significantly superior to ATRA by decreasing relapse in high-risk patients. Overall survival after randomization did not differ (96% vs. 97%; p  = 0.520). Secondary hematopoietic disorders developed in nine patients, secondary malignancies in 11, and grade 3 or more late cardiac comorbidities in three. These late complications did not differ between the two arms.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 692/308/2779/777 / 692/699/1541/1990/283/1897 / Acute myelocytic leukemia / Acute promyeloid leukemia / Adolescent / Adult / Aged / Benzoates - therapeutic use / Cancer Research / Cancer treatment / Chemotherapy / Comorbidity / Complications / Critical Care Medicine / Development and progression / Drug therapy / Female / Follow-Up Studies / Health aspects / Hematology / Humans / Intensive / Internal Medicine / Leukemia / Leukemia, Promyelocytic, Acute - drug therapy / Leukemia, Promyelocytic, Acute - mortality / Leukemia, Promyelocytic, Acute - pathology / Leukocytes / Maintenance / Male / Medicine / Medicine & Public Health / Middle Aged / Neoplasm Recurrence, Local - drug therapy / Neoplasm Recurrence, Local - mortality / Neoplasm Recurrence, Local - pathology / Oncology / Patients / Promyeloid leukemia / Prospective Studies / Randomization / Remission / Remission (Medicine) / Remission Induction / Retinoic acid / Risk groups / Salvage Therapy / Survival / Survival Rate / Tetrahydronaphthalenes - therapeutic use / Tretinoin / Young Adult