Randomized study of imatinib for chronic myeloid leukemia: comparing standard dose escalation with aggressive escalation

• Published in: Blood advances 2019-02, Vol.3 (3), p.312-319
• Main Authors: Miyamura, Koichi, Ohnishi, Kazunori, Ohtake, Shigeki, Usui, Noriko, Nakaseko, Chiaki, Fujita, Hiroyuki, Fujisawa, Shin, Sakura, Toru, Okumura, Hirokazu, Iriyama, Noriyoshi, Emi, Nobuhiko, Fujimaki, Katsumichi, Honda, Sumihisa, Miyazaki, Yasushi, Naoe, Tomoki
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Clinical Trials and Observations; Humans; Imatinib Mesylate - pharmacology; Imatinib Mesylate - therapeutic use; Leukemia, Myeloid, Chronic-Phase - drug therapy; Middle Aged; Prospective Studies; Young Adult
• ISSN: 2473-9529; 2473-9537
• DOI: 10.1182/bloodadvances.2018025981

In 2007, we conducted a prospective randomized study to compare an aggressive dose escalation (group B, n = 123) with the standard dose escalation proposed by European LeukemiaNet (group A, n = 122). In group B, if patients did not achieve a complete cytogenetic response (CCyR) at 3 months or did not achieve a major molecular response (MR3) at 6 months, imatinib was increased to 600 mg. At 6 months CCyR was achieved in 69.4% and 78.7% of patients in groups A and B, respectively. The rate of MR3 at 12 months and 24 months were similar in group A (52.1% and 70.0%) and group B (58.7% and 68.3%). The cumulative incidence of withdrawal by failure without accelerated/blast phase was higher in group A than in group B (9.2% vs 2.5% at 24 months). At 3 and 6 months, the protocol called for the imatinib dose to increase to 600 mg in 90 patients (74.4%) in group B. Among the 42 patients who received increased dose according to the protocol, 25 (60.0%) achieved MR3 at 12 months, whereas only 14 (35.0%) of 40 patients who did not receive an increased dose achieved MR3 (P < .05). The number of patients who withdrew from this study was similar (group A, 20%; group B, 21%). The early aggressive dose escalation failed to produce a better molecular response at 12 months. However, for patients who tolerate imatinib well, but show inadequate response at an early time point, aggressive dose escalation may contribute to achieving a better outcome. This study was registered at http://www.umin.ac.jp/ctr/ as #R000000965. [Display omitted]