A Randomized Trial Comparing Individualized Vs. Non-Individualized Treatment for Elderly Acute Myeloid Leukemia: JALSG GML200 Study

• Published in: Blood 2008-11, Vol.112 (11), p.2961-2961
• Main Authors: Wakita, Atsushi, Ohtake, Shigeki, Takada, Satoru, Yagasaki, Fumiharu, Komatsu, Hirokazu, Miyazaki, Yasushi, Kubo, Koumei, Kimura, Yukihiko, Takeshita, Akihiro, Adachi, Yoko, Kiyoi, Hitoshi, Yamaguchi, Takuhiro, Yoshida, Minoru, Ohnishi, Kazunori, Miyawaki, Shuichi, Naoe, Tomoki, Ueda, Ryuzo, Ohno, Ryuzo
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V112.11.2961.2961

The outcome of elderly patients with acute myeloid leukemia (AML) has not been improved for these three decades, although the incidence is getting increased with the aging of the population in Japan. In the JALSG GML200 study, we prospectively registered all elderly patients with AML during this study irrespective of the eligible criteria,. Since elderly patients are less able to tolerate to intensive cyottoxic intensive chemotherapy, we conducted a randomized study to assess an individualized induction treatment. After consolidation chemotherapy, we evaluated the adjuvant effect of ubenimex (UBX), an anti-leukemia immunomodulator. Method: From April 2000 to August 2005, the JALSG GML200 study registered all newly diagnosed AML patients aged 65 years and over. Patients who satisfied the eligibility criteria were randomized to receive either the individualized therapy (arm B) or non-individualized therapy (arm A). Patients who were not eligible were classified in arm C. Induction therapy of Arm A: enocitabine (BH-AC) 200 mg/m2 on days 1–8, 3 h infusion + daunorubicin (DNR) 40 mg/m2 on days 1–3, 30 min infusion. Arm B: BH-AC 200 mg/m2 on days 1–8, with extension to day 12 according to the results of bone marrow examination on days 7 and 10, + DNR 40 mg/m2 on days 1–3, with extension on day 12 depending on the results of bone marrow examination on days 7 and 10. Patients who achieved a complete response (CR) were randomized again to receive immuno-therapy with ubenimex (group UY) or without ubenimex (group UN). Consolidation therapy consisted of three courses: BH-AC 200 mg/m2 on days 1–5 + Mitoxantrone (MIT) 7 mg/m2 on days 1–3,BH-AC 200 mg/m2 on days 1–5 + DNR 30 mg/m2 on days 1–2, ETP 100 mg/m2 on days 1–3,BH-AC 200 mg/m2 on days 1–5 + ACR 14 mg/m2 on days 1–5. Result: Of the 374 patients registered, 244 patients were eligible for randomization to arms A and B, and 235 patients were evaluable. The median patients' age of arms A, B and C were 70 (range, 65–79), 71 (range, 65–79), and 74 years (range, 65–92), respectively. CR rate of arm A was 63.2% and that of arm B was 65.3% (p = 0.75). CR rates of male and female patients significantly differed in each arm (arm A: male 55.4% vs. female 76.3%, p=0.053, arm B: male 53.1% vs. female 80.0%, p=0.008). Overall survival rates at 3 years of arms A and B were 25.5% and 21.5% (p = 0.56), respectively. With reference to survival with or without ubenimex in patients who achieved CR, the overall survival rate at 3 year