TY - JOUR
T1 - Assessment of BCR-ABL1 transcript levels at 3 months is the only requirement for predicting outcome for patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors
AU - Marin, David
AU - Ibrahim, Amr R.
AU - Lucas, Claire
AU - Gerrard, Gareth
AU - Wang, Lihui
AU - Szydlo, Richard M.
AU - Clark, Richard E.
AU - Apperley, Jane F.
AU - Milojkovic, Dragana
AU - Bua, Marco
AU - Pavlu, Jiri
AU - Paliompeis, Christos
AU - Reid, Alistair
AU - Rezvani, Katayoun
AU - Goldman, John M.
AU - Foroni, Letizia
PY - 2012/1/20
Y1 - 2012/1/20
N2 - Purpose: We studied BCR-ABL1 transcript levels in patients with chronic myeloid leukemia in chronic phase (CML-CP) at 3, 6, and 12 months after starting imatinib to identify molecular milestones that would predict for overall survival (OS) and other outcomes more reliably than serial marrow cytogenetics. Patients and Methods: We analyzed 282 patients with CML-CP who received imatinib 400 mg/d as first-line therapy followed by dasatinib or nilotinib if treatment with imatinib failed. We used a receiver operating characteristic curve to identify the cutoffs in transcript levels at 3, 6, and 12 months that would best predict patient outcome. We validated our findings in an independent cohort of 95 patients treated elsewhere. Results: Patients with transcript levels of more than 9.84% (n = 68) at 3 months had significantly lower 8-year probabilities of OS (56.9% v 93.3%; P < .001), progression-free survival, cumulative incidence of complete cytogenetic response, and complete molecular response than those with higher transcript levels. Similarly, transcript levels of more than 1.67% (n = 87) at 6 months and more than 0.53% (n = 93) at 12 months identified high-risk patients. However, transcript levels at 3 months were the most strongly predictive for the various outcomes. When we compared OS for the groups defined molecularly at 6 and 12 months with the usual cytogenetic milestones, categorization by transcript numbers was the only independent predictor for OS (relative risk, 0.207; P < .001 and relative risk, 0.158; P < .001, respectively). Conclusion: A single measurement of BCR-ABL1 transcripts performed at 3 months is the best way to identify patients destined to fare poorly, thereby allowing early clinical intervention.
AB - Purpose: We studied BCR-ABL1 transcript levels in patients with chronic myeloid leukemia in chronic phase (CML-CP) at 3, 6, and 12 months after starting imatinib to identify molecular milestones that would predict for overall survival (OS) and other outcomes more reliably than serial marrow cytogenetics. Patients and Methods: We analyzed 282 patients with CML-CP who received imatinib 400 mg/d as first-line therapy followed by dasatinib or nilotinib if treatment with imatinib failed. We used a receiver operating characteristic curve to identify the cutoffs in transcript levels at 3, 6, and 12 months that would best predict patient outcome. We validated our findings in an independent cohort of 95 patients treated elsewhere. Results: Patients with transcript levels of more than 9.84% (n = 68) at 3 months had significantly lower 8-year probabilities of OS (56.9% v 93.3%; P < .001), progression-free survival, cumulative incidence of complete cytogenetic response, and complete molecular response than those with higher transcript levels. Similarly, transcript levels of more than 1.67% (n = 87) at 6 months and more than 0.53% (n = 93) at 12 months identified high-risk patients. However, transcript levels at 3 months were the most strongly predictive for the various outcomes. When we compared OS for the groups defined molecularly at 6 and 12 months with the usual cytogenetic milestones, categorization by transcript numbers was the only independent predictor for OS (relative risk, 0.207; P < .001 and relative risk, 0.158; P < .001, respectively). Conclusion: A single measurement of BCR-ABL1 transcripts performed at 3 months is the best way to identify patients destined to fare poorly, thereby allowing early clinical intervention.
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U2 - 10.1200/JCO.2011.38.6565
DO - 10.1200/JCO.2011.38.6565
M3 - Article
C2 - 22067393
AN - SCOPUS:84862907694
SN - 0732-183X
VL - 30
SP - 232
EP - 238
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 3
ER -