Abstract
The aim of this phase IV study was to (1) to define efficacy of escalating dose imatinib in chronic myeloid leukemia (CML) patients showing suboptimal response to standard dose imatinib and (2) to find markers that predict the response to escalating doses of imatinib. CML patients in chronic phase (CP) who failed to achieve optimal response with 400 mg/day imatinib or patients in accelerated phase (AP) or blast crisis (BC) who failed to achieve complete hematologic response after 3 months of 400–600 mg/day imatinib were enrolled. CP patients received 600 mg/day, while AP/BC patients received 600–800 mg/day imatinib. Patients received imatinib for at least 12 months or until the disease progression or intolerable toxicity. Along with cytogenetic response (CyR), molecular response was assessed with BCR-ABL/ABL ratio. Baseline BCR-ABL gene mutation test was performed. Seventy-one patients (median age, 49.0 years, M:F = 50:21) received escalated dose imatinib. Grade 3 edema in two patients was the only nonhematologic toxicities more than grade 2. For evaluable patients, 30.8% of patients achieved CCyR at 6 months, and median time to treatment failure (TTFx) was 18.0 months. TTFx was longer in patients who achieved greater than 50% reduction in BCR-ABL/ABL within 6 months (early molecular responder (EMR)) compared with those who did not (non-EMR; p < 0.001). Of 31 patients who had mutational status data, three had mutation. All mutants failed to achieve CCyR. In conclusion, escalated dose imatinib shows considerable efficacy with tolerable toxicity in CML patients showing suboptimal response to standard dose imatinib. EMR is an early predictive marker for positive imatinib response.
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This work was supported by a grant from the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (0405-BC02-0604-0004).
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The Korean Society of Hematology CML working party investigators are listed in the Appendix.
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The investigators for the Korean Society of Hematology CML Working Party were as follows: President: Seonyang Park; Secretary: Inho Kim; Sung-Soo Yoon, Hyeoung-Joon Kim, Sang Kyun Sohn, Jooseop Chung, Ho-Jin Shin, Chul Soo Kim, Min Kyoung Kim, Chul Won Jung, Byung-Soo Kim, Yu-Kyung Kim, Jae Seog Kim, Jin Seog Kim, Jae-Yong Kwak, Na-Ri Lee, Yoo-Hong Min, Chong Won Park, Suk Joong Oh, Jung-Hee Lee, Dae Young Zang, Jun-Won Cheong, Deog-Yeon Jo, Bong Seog Kim, Sun-Hee Kim, Hun-Mo Ryu, Seung-Hyun Nam, Yeung-Chul Moon, Kyung-Tae Park, Mu-Rim Park, Eunkyung Park, Jae-Hoo Park, Chi-Hyung Park, Soo-Mee Bang, Sung-Hwa Bae, Moon-Hee Lee, Sung-Soo Jang, Jun-ho Jang, Choon-Hae Chung, Hyun-Sook Chi, Sam-Im Choi, and Jung-Lim Lee.
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Koh, Y., Kim, I., Yoon, SS. et al. Phase IV study evaluating efficacy of escalated dose of imatinib in chronic myeloid leukemia patients showing suboptimal response to standard dose imatinib. Ann Hematol 89, 725–731 (2010). https://doi.org/10.1007/s00277-010-0910-8
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DOI: https://doi.org/10.1007/s00277-010-0910-8