A prospective analysis of clinical efficacy and safety in chronic myeloid leukemia-chronic phase patients with imatinib resistance or intolerance as evaluated using European LeukemiaNet 2013 criteria

作者：Murai Kazunori; Akagi Tomoaki; Shimosegawa Kenji; Sugawara Tomohiro; Ishizawa Kenichi; Ito Shigeki; Murai Keiko; Motegi Mutsuhito; Yokoyama Hisayuki; Noji Hideyoshi; Tajima Katsushi; Kimura Jun; Chou Takaaki; Ogawa Kazuei; Harigae Hideo; Kubo Kohmei; Oba Koji; Sakamoto Junichi; Ishida Yoji^*

来源：European Journal of Haematology, 2015, 95(6): 558-565.

DOI：10.1111/ejh.12536

• chronic myeloid leukemia
• dasatinib
• major molecular response
• molecular response > = 4.5 log reduction
• European LeukemiaNet 2013 recommendations

Background: We conducted a phase II study to evaluate the efficacy and safety of dasatinib in Japanese patients with imatinib-resistant or imatinib-intolerant chronic myeloid leukemia (CML). Methods: From 2009 to 2011, 54 CML-chronic phase (CP) patients with resistance (n = 40) or intolerance (n = 25) to imatinib were registered to undergo dasatinib treatment. Eleven patients showed both resistance and intolerance to imatinib. Coincidentally, the resistance criteria in this study were the same as a non-optimal response to tyrosine kinase inhibitors (TKIs) as defined in the European LeukemiaNet (ELN) 2013 recommendations. Results: The overall incidence rate of major molecular response (MMR) at 12 months was 62.3% (n = 47). Forty patients with resistance to imatinib who were 'warning' and 'failure' patients based on the ELN 2013 recommendations were assessed; cumulative MMR and MR4.5 rates were 62.5% (n = 39) and 21.0% (n = 40), respectively, at 12 months. Twelve patients who showed a BCR-ABL transcript level >1% on the international scale did not achieve a MMR or discontinued dasatinib treatment because of insufficient effects. With regard to safety issues, grade 3/4 non-hematologic adverse events (AEs) were infrequent. Conclusions: Patients with non-optimal responses (who meet ELN 2013 warning and failure criteria) to imatinib should be switched quickly to dasatinib, which is less toxic in CML-CP patients, to improve their prognoses. A BCR-ABL1 IS of <1% at 3 months of dasatinib administration is a landmark for good therapeutic outcome.

• 出版日期2015-12