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Prediction for sustained deep molecular response of BCR‐ABL1 levels in patients with chronic myeloid leukemia in chronic phase
Author(s) -
Sasaki Koji,
Kantarjian Hagop,
O'Brien Susan,
Ravandi Farhad,
Konopleva Marina,
Borthakur Gautam,
GarciaManero Guillermo,
Wierda William,
Daver Naval,
Ferrajoli Alessandra,
Takahashi Koichi,
Jain Preetesh,
Rios Mary Beth,
Pierce Sherry,
Jabbour Elias,
Cortes Jorge E.
Publication year - 2018
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.31187
Subject(s) - medicine , discontinuation , myeloid leukemia , percentile , quantile regression , digital polymerase chain reaction , linear regression , regression analysis , gastroenterology , oncology , polymerase chain reaction , statistics , biology , genetics , mathematics , gene
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 . © 2017 American Cancer Society .