"M3-M6" Molecular Response Evolution As Early Predictor of Outcome Considering Generic Vs Branded TKIs for Chronic Myeloid Leukemia (CML): An Argentine Multicentric Study

• Published in: Blood 2016-12, Vol.128 (22), p.5445-5445
• Main Authors: Giere, Isabel Amanda, Mela Osorio, María Jose, Klosowski, Federico Andrés, Debus, Mariana, Sackmann, Federico, Pavlovsky, Miguel A, Fernandez, Isolda, Moiraghi, Elena Beatriz, Varela, Ana Inés, Perez, Mariel Ana, Pose Cabarcos, Julio M., Bendek, Georgina, Mariano, Romina, Palmer, Silvina, Enrico, Alicia, Annetta, Isabel Cristina, Brodsky, Andres L., Intile, Dante, Pavlovsky, Carolina
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V128.22.5445.5445

Introduction: Early reduction of BCR-ABL transcript level has been associated with improved outcomes in CML treatment. Inability to achieve early molecular response(MR) at 3 months (M3>10%) is considered a predictor factor for unfavourable outcome. However, the kinetics of BCR-ABL transcript level reduction measured at early time points have shown to be an independent predictor of response.The aim of this analysis was to determine whether the "M3-M6" status is critical to categorize CML patients (pts) focusing in high-risk group. Method: Molecular monitoring was performed in all pts prior treatment (M0), at months 3 (M3), 6 (M6), 12 (M12) and every 6 months thereafter, applying Q-PCR method according international recommendations. Results of BCR-ABL1 transcript level were reported on the international scale as IS-BCR-ABL %. Optimal responses: M3≤10%, M6≤1%, M12≤0,1%. Deep responses (MR4.0): ≤0,01% or undetectable/10.000 ABL copies. Results: A total of 70 CML pts were included, median age 49 (19-82), female 39%. First line treatment: sustained branded 81% and generic 19% TKIs. Imatinib 59%, Dasatinib and Nilotinib 41%. Sokal risk score: low (L) 51%, intermediate (In) and high (H) 49%. Optimal responses at molecular milestones: 75% at M3, 72% at M6, 61% at M12 and 53% pts achieved MR4.0. Event-free survival (EFS) was evaluated according to time point M3: M3≤10% group had significantly better EFS compared with the M3>10% (96% vs 70%; P=0.028). M3-M6 status defined 4 groups of pts: M3≤10%-M6≤1%, M3≤10%-M6>1%, M3>10%-M6≤1%, M3>10%-M6>1%. Molecular response evolution by M3-M6 status is described in Table 1. EFS stratified by groups according to combined M3-M6 responses showed significant differences: 92% for group 1, 87% for group 2, 68% for group 3, 54% for group 4. (P=0.002). M6 time point was shown to be critical in 32 high-risk pts (H+In): 17 pts with M6 ≤1% showed significant differences in MR4.0 achievement compared to 15 pts with M6 >1% (82% vs 27% P=0.02). Better EFS was observed in this high-risk group under branded vs generic TKIs treatment (97% vs 54% P=0.04). Statistical differences in deep responses and MMR at M12 were observed between branded and generic TKIs independently of Sokal risk (P=0.06, P=0.02). Conclusions: M3≤10% pts showed a favourable evolution with better EFS than M3>10% group. However not all patients with M31%. In pts with M3 >10%