Katsuji Shinagawa1, Masamitsu Yanada2, Toru Sakura1, Yasunori Ueda1, Masashi Sawa1, Junichi Miyatake1, Nobuaki Dobashi1, Minoru Kojima1, Yoshihiro Hatta1, Nobuhiko Emi1, Shigehisa Tamaki1, Hiroshi Gomyo1, Etsuko Yamazaki1, Katsumichi Fujimaki1, Norio Asou1, Keitaro Matsuo1, Shigeki Ohtake1, Yasushi Miyazaki1, Kazunori Ohnishi1, Yukio Kobayashi1, Tomoki Naoe1. 1. Katsuji Shinagawa, Okayama University Hospital, Okayama; Masamitsu Yanada and Nobuhiko Emi, Fujita Health University School of Medicine, Toyoake; Toru Sakura, Saiseikai Maebashi Hospital, Maebashi; Yasunori Ueda, Kurashiki Central Hospital, Kurashiki; Masashi Sawa, Anjo Kosei Hospital, Anjo; Junichi Miyatake, Kinki University Faculty of Medicine, Osakasayama; Nobuaki Dobashi, Jikei University School of Medicine; Yoshihiro Hatta, Nihon University School of Medicine; Yukio Kobayashi, National Cancer Center Hospital, Tokyo; Minoru Kojima, Tokai University School of Medicine, Isehara; Shigehisa Tamaki, Ise Red Cross Hospital, Ise; Hiroshi Gomyo, Hyogo Cancer Center, Akashi; Etsuko Yamazaki, Graduate School of Medicine and Faculty of Medicine, Yokohama City University, Yokohama; Katsumichi Fujimaki, Fujisawa City Hospital, Fujisawa; Norio Asou, International Medical Center, Saitama Medical University, Hidaka; Keitaro Matsuo, Kyushu University Faculty of Medical Sciences, Fukuoka; Shigeki Ohtake, Kanazawa University Graduate School of Medical Sciences, Kanazawa; Yasushi Miyazaki, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki; Kazunori Ohnishi, Hamamatsu University School of Medicine, Hamamatsu; and Tomoki Naoe, Nagoya University Graduate School of Medicine and National Hospital Organization Nagoya Medical Center, Nagoya, Japan. 2. Katsuji Shinagawa, Okayama University Hospital, Okayama; Masamitsu Yanada and Nobuhiko Emi, Fujita Health University School of Medicine, Toyoake; Toru Sakura, Saiseikai Maebashi Hospital, Maebashi; Yasunori Ueda, Kurashiki Central Hospital, Kurashiki; Masashi Sawa, Anjo Kosei Hospital, Anjo; Junichi Miyatake, Kinki University Faculty of Medicine, Osakasayama; Nobuaki Dobashi, Jikei University School of Medicine; Yoshihiro Hatta, Nihon University School of Medicine; Yukio Kobayashi, National Cancer Center Hospital, Tokyo; Minoru Kojima, Tokai University School of Medicine, Isehara; Shigehisa Tamaki, Ise Red Cross Hospital, Ise; Hiroshi Gomyo, Hyogo Cancer Center, Akashi; Etsuko Yamazaki, Graduate School of Medicine and Faculty of Medicine, Yokohama City University, Yokohama; Katsumichi Fujimaki, Fujisawa City Hospital, Fujisawa; Norio Asou, International Medical Center, Saitama Medical University, Hidaka; Keitaro Matsuo, Kyushu University Faculty of Medical Sciences, Fukuoka; Shigeki Ohtake, Kanazawa University Graduate School of Medical Sciences, Kanazawa; Yasushi Miyazaki, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki; Kazunori Ohnishi, Hamamatsu University School of Medicine, Hamamatsu; and Tomoki Naoe, Nagoya University Graduate School of Medicine and National Hospital Organization Nagoya Medical Center, Nagoya, Japan. myanada@fujita-hu.ac.jp.
Abstract
PURPOSE: The introduction of all-trans-retinoic acid (ATRA) has significantly improved outcomes for acute promyelocytic leukemia (APL), although a subset of patients still suffer relapse. The purpose of this study was to evaluate the role of maintenance therapy with the synthetic retinoid tamibarotene in APL. PATIENTS AND METHODS: Patients with newly diagnosed APL in molecular remission at the end of consolidation therapy were randomly assigned to receive ATRA or tamibarotene, both orally, for 14 days every 3 months for up to 2 years. RESULTS: A total of 347 patients were enrolled. Of the 344 eligible patients, 319 (93%) achieved complete remission. After completing three courses of consolidation therapy, 269 patients underwent maintenance random assignment. The relapse-free survival (RFS) rate at 4 years was 84% for the ATRA arm and 91% for the tamibarotene arm (hazard ratio [HR], 0.54; 95% CI, 0.26 to 1.13). When the analysis was restricted to 52 high-risk patients with an initial WBC count ≥ 10.0 × 10(9)/L, the intergroup difference was statistically significant, with 4-year RFS rates of 58% for the ATRA arm and 87% for the tamibarotene arm (HR, 0.26; 95% CI, 0.07 to 0.95). For patients with non-high-risk disease, the HR was 0.82 (95% CI, 0.32 to 2.01). The test for interaction between treatment effects and these subgroups resulted in P = .075. Both treatments were generally well tolerated. CONCLUSION: In this trial, no difference was detected between ATRA and tamibarotene for maintenance therapy. In an exploratory analysis, there was a suggestion of improved efficacy of tamibarotene in high-risk patients, but this requires further study.
RCT Entities:
PURPOSE: The introduction of all-trans-retinoic acid (ATRA) has significantly improved outcomes for acute promyelocytic leukemia (APL), although a subset of patients still suffer relapse. The purpose of this study was to evaluate the role of maintenance therapy with the synthetic retinoidtamibarotene in APL. PATIENTS AND METHODS: Patients with newly diagnosed APL in molecular remission at the end of consolidation therapy were randomly assigned to receive ATRA or tamibarotene, both orally, for 14 days every 3 months for up to 2 years. RESULTS: A total of 347 patients were enrolled. Of the 344 eligible patients, 319 (93%) achieved complete remission. After completing three courses of consolidation therapy, 269 patients underwent maintenance random assignment. The relapse-free survival (RFS) rate at 4 years was 84% for the ATRA arm and 91% for the tamibarotene arm (hazard ratio [HR], 0.54; 95% CI, 0.26 to 1.13). When the analysis was restricted to 52 high-risk patients with an initial WBC count ≥ 10.0 × 10(9)/L, the intergroup difference was statistically significant, with 4-year RFS rates of 58% for the ATRA arm and 87% for the tamibarotene arm (HR, 0.26; 95% CI, 0.07 to 0.95). For patients with non-high-risk disease, the HR was 0.82 (95% CI, 0.32 to 2.01). The test for interaction between treatment effects and these subgroups resulted in P = .075. Both treatments were generally well tolerated. CONCLUSION: In this trial, no difference was detected between ATRA and tamibarotene for maintenance therapy. In an exploratory analysis, there was a suggestion of improved efficacy of tamibarotene in high-risk patients, but this requires further study.
Authors: David Sanford; Francesco Lo-Coco; Miguel A Sanz; Eros Di Bona; Steven Coutre; Jessica K Altman; Meir Wetzler; Steven L Allen; Farhad Ravandi; Hagop Kantarjian; Jorge E Cortes Journal: Br J Haematol Date: 2015-07-24 Impact factor: 6.998
Authors: Michael R McKeown; M Ryan Corces; Matthew L Eaton; Chris Fiore; Emily Lee; Jeremy T Lopez; Mei Wei Chen; Darren Smith; Steven M Chan; Julie L Koenig; Kathryn Austgen; Matthew G Guenther; David A Orlando; Jakob Lovén; Christian C Fritz; Ravindra Majeti Journal: Cancer Discov Date: 2017-07-20 Impact factor: 39.397