TY - JOUR
T1 - Prediction for sustained deep molecular response of BCR-ABL1 levels in patients with chronic myeloid leukemia in chronic phase
AU - Sasaki, Koji
AU - Kantarjian, Hagop
AU - O'Brien, Susan
AU - Ravandi, Farhad
AU - Konopleva, Marina
AU - Borthakur, Gautam
AU - Garcia-Manero, Guillermo
AU - Wierda, William
AU - Daver, Naval
AU - Ferrajoli, Alessandra
AU - Takahashi, Koichi
AU - Jain, Preetesh
AU - Rios, Mary Beth
AU - Pierce, Sherry
AU - Jabbour, Elias
AU - Cortes, Jorge E.
N1 - Funding Information:
This study was partly supported by MD Anderson Cancer Center Support Grant CA016672 and the National Cancer Institute (award P01 CA049639). We thank Dr. O. Miura (Tokyo Medical and Dental University) for useful advice.
Publisher Copyright:
© 2017 American Cancer Society
PY - 2018/3/15
Y1 - 2018/3/15
N2 - BACKGROUND: The achievement of a sustained deep molecular response is a goal of increasing relevance because it opens the possibility of treatment discontinuation. The objective of this analysis was to develop a prediction model for a sustained molecular response with BCR-ABL1 level <0.0032% on the international scale (MR 4.5 ) for at least 2 years according to BCR-ABL1 levels achieved within the first 12 months of therapy. METHODS: Data for 603 patients with newly diagnosed chronic myeloid leukemia in chronic phase in consecutive prospective clinical trials were analyzed. The best fit average molecular response was defined by robust linear regression models, with which the average molecular levels were defined. The minimum acceptable molecular response was defined by quantile regression for the 95th percentile, with which the worst 5% BCR-ABL1 levels were identified. RESULTS: In 603 patients with a median follow-up of 103 months, 2002 BCR-ABL1–level data points within 1 year of tyrosine kinase inhibitors were identified. The regression equation for the best fit average levels for a sustained MR 4.5 was Log 10 (PCR) = −0.1424 × (Months) – 0.8668, and the regression equation for minimum acceptable levels was Log 10 (PCR) = −0.1403 × (Months) + 0.6142 (where PCR indicates polymerase chain reaction). To achieve a sustained MR 4.5 , the best fit average levels were 0.051%, 0.019%, 0.007%, and 0.003% at 3, 6, 9, and 12 months, respectively; the minimum acceptable levels were 1.561%, 0.592%, 0.225%, and 0.085% at 3, 6, 9, and 12 months, respectively. CONCLUSIONS: This model proposes optimal values that predict the highest probability of reaching such a goal. These values can be used to guide therapy when a sustained MR 4.5 is the objective. Cancer 2018;124:1160-8.
AB - BACKGROUND: The achievement of a sustained deep molecular response is a goal of increasing relevance because it opens the possibility of treatment discontinuation. The objective of this analysis was to develop a prediction model for a sustained molecular response with BCR-ABL1 level <0.0032% on the international scale (MR 4.5 ) for at least 2 years according to BCR-ABL1 levels achieved within the first 12 months of therapy. METHODS: Data for 603 patients with newly diagnosed chronic myeloid leukemia in chronic phase in consecutive prospective clinical trials were analyzed. The best fit average molecular response was defined by robust linear regression models, with which the average molecular levels were defined. The minimum acceptable molecular response was defined by quantile regression for the 95th percentile, with which the worst 5% BCR-ABL1 levels were identified. RESULTS: In 603 patients with a median follow-up of 103 months, 2002 BCR-ABL1–level data points within 1 year of tyrosine kinase inhibitors were identified. The regression equation for the best fit average levels for a sustained MR 4.5 was Log 10 (PCR) = −0.1424 × (Months) – 0.8668, and the regression equation for minimum acceptable levels was Log 10 (PCR) = −0.1403 × (Months) + 0.6142 (where PCR indicates polymerase chain reaction). To achieve a sustained MR 4.5 , the best fit average levels were 0.051%, 0.019%, 0.007%, and 0.003% at 3, 6, 9, and 12 months, respectively; the minimum acceptable levels were 1.561%, 0.592%, 0.225%, and 0.085% at 3, 6, 9, and 12 months, respectively. CONCLUSIONS: This model proposes optimal values that predict the highest probability of reaching such a goal. These values can be used to guide therapy when a sustained MR 4.5 is the objective. Cancer 2018;124:1160-8.
KW - best fit average
KW - chronic myeloid leukemia
KW - minimum acceptable
KW - molecular response with BCR-ABL1 level<0.0032% on the international scale (MR )
KW - tyrosine kinase inhibitor
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U2 - 10.1002/cncr.31187
DO - 10.1002/cncr.31187
M3 - Article
C2 - 29266206
AN - SCOPUS:85038424801
SN - 0008-543X
VL - 124
SP - 1160
EP - 1168
JO - Cancer
JF - Cancer
IS - 6
ER -