TY - JOUR
T1 - Prognostic significance of additional chromosomal abnormalities at the time of diagnosis in patients with chronic myeloid leukemia treated with frontline tyrosine kinase inhibitors
AU - Alhuraiji, Ahmad
AU - Kantarjian, Hagop
AU - Boddu, Prajwal
AU - Ravandi, Farhad
AU - Borthakur, Gautam
AU - DiNardo, Courtney
AU - Daver, Naval
AU - Kadia, Tapan
AU - Pemmaraju, Naveen
AU - Pierce, Sherry
AU - Garcia-Manero, Guillermo
AU - Wierda, William
AU - Verstovsek, Srdan
AU - Jabbour, Elias
AU - Cortes, Jorge
N1 - Funding Information:
University of Texas MD Anderson Cancer Center, Grant/Award Number: P30 CA16672, P01 CA049639 (PI, Dr. Richard Champlin); National Cancer Institute (NCI). Jorge Cortes is the recipient of a grant from the NCI (P01 CA049639)
Publisher Copyright:
© 2017 Wiley Periodicals, Inc.
PY - 2018/1
Y1 - 2018/1
N2 - Additional cytogenetic abnormalities (ACA) are considered a high risk feature in chronic myeloid leukemia (CML). However, its prognostic significance at the time of diagnosis in the setting of new tyrosine kinase inhibitors (TKIs) is less well understood. Patients with CML in CP with or without ACA at diagnosis treated with frontline TKIs in prospective clinical trials were analyzed for outcomes. Among 603 patients treated, 29 (5%) had ACA. Patients with ACA included 2 of 72 (2.8%) treated with imatinib 400 mg, 9 of 207 (4.3%) with imatinib 800 mg, 10 of 148 (6.7%) with dasatinib, 6 of 126 (4.7%) with nilotinib, and 2 of 50 (4%) with ponatinib. There was a significantly higher rate of complete cytogenetic response (CCyR) at 6 months in patients without ACA (P =.02). However cumulative CCyR and major molecular response (MMR) rates were not different. Similarly, MR4.0 and MR4.5 rates were similar for both groups; two CML-ACA patients maintained MR 4.5 for at least 2 years. At 5 years, ACA at diagnosis did not significantly impact transformation-free, failure-free, event-free, or overall survival expectations. Acknowledging small sample size estimates, response rates and survival outcomes were comparable in CP with ACA irrespective of whether chromosomal abnormalities were “major route” or other. The presence of ACA at diagnosis does not confer worse prognosis for patients with CML treated with TKI. Thus, the presence of ACA at diagnosis should not alter treatment strategies in these patients.
AB - Additional cytogenetic abnormalities (ACA) are considered a high risk feature in chronic myeloid leukemia (CML). However, its prognostic significance at the time of diagnosis in the setting of new tyrosine kinase inhibitors (TKIs) is less well understood. Patients with CML in CP with or without ACA at diagnosis treated with frontline TKIs in prospective clinical trials were analyzed for outcomes. Among 603 patients treated, 29 (5%) had ACA. Patients with ACA included 2 of 72 (2.8%) treated with imatinib 400 mg, 9 of 207 (4.3%) with imatinib 800 mg, 10 of 148 (6.7%) with dasatinib, 6 of 126 (4.7%) with nilotinib, and 2 of 50 (4%) with ponatinib. There was a significantly higher rate of complete cytogenetic response (CCyR) at 6 months in patients without ACA (P =.02). However cumulative CCyR and major molecular response (MMR) rates were not different. Similarly, MR4.0 and MR4.5 rates were similar for both groups; two CML-ACA patients maintained MR 4.5 for at least 2 years. At 5 years, ACA at diagnosis did not significantly impact transformation-free, failure-free, event-free, or overall survival expectations. Acknowledging small sample size estimates, response rates and survival outcomes were comparable in CP with ACA irrespective of whether chromosomal abnormalities were “major route” or other. The presence of ACA at diagnosis does not confer worse prognosis for patients with CML treated with TKI. Thus, the presence of ACA at diagnosis should not alter treatment strategies in these patients.
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U2 - 10.1002/ajh.24943
DO - 10.1002/ajh.24943
M3 - Article
C2 - 29027261
AN - SCOPUS:85033486402
SN - 0361-8609
VL - 93
SP - 84
EP - 90
JO - American Journal of Hematology
JF - American Journal of Hematology
IS - 1
ER -