Assessment of BCR-ABL1 Transcript Levels At 3 Months Is the Only Requirement for Predicting Outcome for Patients with Chronic Myeloid Leukemia Treated with Imatinib

• Published in: Blood 2011-11, Vol.118 (21), p.1680-1680
• Main Authors: Milojkovic, Dragana, Ibrahim, Amr R, Foroni, Letizia, Lucas, Claire, Gerrard, Gareth, Wang, Lihui, Szydlo, Richard M, Clark, Richard E, Apperley, Jane F, Bua, Marco, Pavlu, Jiri, Paliompeis, Christos, Reid, Alistair, Rezvani, Katy, Goldman, John M, Marin, David
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V118.21.1680.1680

Abstract 1680 We studied BCR-ABL1 transcript levels in patients with CML in chronic phase at 3, 6 and 12 months after starting imatinib to identify molecular milestones that would predict for overall survival and other outcomes more reliably than serial marrow cytogenetics. We analyzed 282 patients with CML-CP who received imatinib 400 mg/day as first line therapy followed by dasatinib or nilotinib if they failed imatinib. The median age was 46.3 years (range 13–86.4), 157 (55.7%) patients were male. The Sokal risk distribution was: 31.8% low, 40.1% intermediate and 28.1% high. The median follow-up was 69 months (range 17–131). BCR-ABL1 transcripts were analyzed in the peripheral blood at 12 week intervals using RQ-PCR. Results were expressed as percentage ratios relative to an ABL internal control and converted to the international scale. Complete molecular response (CMR) was defined as two consecutive samples with no detectable transcripts with the ABL1 control >40,000 copies (the median ABL control in the CMR samples was 84,000). We employed a ROC curve to identify the cut-offs in transcript levels at 3, 6 and 12 months that would best predict patient outcome. Patients with transcript levels >9.84% (n=68) at 3 months had significantly lower 8-year probabilities of overall survival (OS) (56.9% vs 93.3%, p1.67% (n=87) at 6 months and >0.53% (n=93) at 12 months identified poor 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 use of the usual cytogenetic milestones, categorization by transcript numbers was the only independent predictor for OS (RR= 0.207, p