Publication Date:
2013-11-15
Description:
Objectives To analyze the molecular response during the first trimester of nilotinib therapy in newly diagnosed CML-CP patients. Hypothesis The values of BCR-ABL ratios during the first trimester of nilotinib treatment, and the kinetic of their descent, could be predictive of molecular response thereafter. Patients ENEST1st (NCT01061177) is an open-label study of nilotinib 300 mg twice daily in adults with newly diagnosed BCR-ABL+ CML-CP. Imatinib pretreatment was not allowed. Methods BCR-ABLIS and BCR-ABL/GUS ratios were measured previously to nilotinib, and fortnightly thereafter until the 3rd month (m), and at 6, 12 and 18 m. Sokal, Euro and Eutos scores were calculated with data at diagnosis. BCR-ABL values were centrally measured in an ELN-EUTOS certified laboratory. Molecular response was classified by ELN2013 recommendations. As the linearity of values of BCR-ABL using ABL as control is questionable, when ratios are higher than 10%, only baseline BCR-ABL/GUS ratios were used when analyzing the molecular response using GUS as control. The kinetic of the descent was calculated using the ratio of a given time compared with that of an earlier time, and measuring slopes. Logistic regressions and ROC analysis have been used, calculating positive and negative predictive values (PPV and NPV) Results 61 patients were included. 1 patient was excluded of the analysis because of lack of molecular data (baseline). Out of 60 patients, 10 abandoned during the first 18 m because of AE’ s. Those patients have been classified as non-responders after the time they went off-study. Risk distribution: Sokal (L, I, H): 57%, 32%, 11.7% Euro: 52%, 45%, 3%) Eutos (L, H): 92%, 8%). Outcomes and Molecular response: No patient died or transformed during the follow-up. MR4.5 at 18 M has been obtained in 30% of the patients. The ELN 2013 molecular milestones for optimal response at 3,6,12 and thereafter were obtained in 97%, 93%, 83%, and 70%, respectively.(Table) Predictive variables of response: (Table). Major molecular response (²0.1%) (BCR-ABL/ABL, BCR-ABL/GUS). At 3MBaseline BCR-ABL/GUS ratios were significantly different between responders and non-responders (22,1±23,1 vs 41,5± 38,1, p=0.05). For both control genes, the multivariate analysis disclosed that the independent and significant variable was the ratio at 45d. The ROC analysis disclosed a cut-off of 3.28 (PPV: 83% NPV: 80%). [OR: 20(4.4- 90) p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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