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

and the Japanese Adult Leukemia Study Group

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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/m2 daily), and 134 to tamibarotene (6 mg/m2 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 × 109/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.

Original languageEnglish
JournalLeukemia
DOIs
Publication statusAccepted/In press - Jan 1 2018

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Acute Promyelocytic Leukemia
Tretinoin
Maintenance
Recurrence
Survival
Random Allocation
Consolidation Chemotherapy
Comorbidity
Leukocytes
tamibarotene
Drug Therapy
Neoplasms

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Tamibarotene maintenance improved relapse-free survival of acute promyelocytic leukemia : a final result of prospective, randomized, JALSG-APL204 study. / and the Japanese Adult Leukemia Study Group.

In: Leukemia, 01.01.2018.

Research output: Contribution to journalArticle

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abstract = "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/m2 daily), and 134 to tamibarotene (6 mg/m2 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 × 109/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.",
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AU - Takeshita, Akihiro

AU - Asou, Norio

AU - Atsuta, Yoshiko

AU - Sakura, Toru

AU - Ueda, Yasunori

AU - Sawa, Masashi

AU - Dobashi, Nobuaki

AU - Taniguchi, Yasuhiro

AU - Suzuki, Rikio

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AU - Hagihara, Maki

AU - Fujimaki, Katsumichi

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AU - Obata, Yukako

AU - Fujita, Hiroyuki

AU - Yanada, Masamitsu

AU - Maeda, Yoshinobu

AU - Usui, Noriko

AU - Kobayashi, Yukio

AU - Kiyoi, Hitoshi

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AU - Matsumura, Itaru

AU - Naoe, Tomoki

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