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A prospective analysis of clinical efficacy and safety in chronic myeloid leukemia‐chronic phase patients with imatinib resistance or intolerance as evaluated using E uropean L eukemia N et 2013 criteria
Author(s) -
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
Publication year - 2015
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.12536
Subject(s) - medicine , dasatinib , imatinib , imatinib mesylate , nilotinib , myeloid leukemia , tyrosine kinase inhibitor , adverse effect , cumulative incidence , incidence (geometry) , oncology , transplantation , cancer , physics , optics
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 ( TKI s) 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 MR 4.5 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 ( AE s) 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 ‐ ABL 1 IS of <1% at 3 months of dasatinib administration is a landmark for good therapeutic outcome.