Evaluation of 5‐year imatinib treatment of 458 patients with CP‐CML in routine clinical practice and prognostic impact of different BCR‐ABL cutoff levels

Abstract

We evaluated responses to the treatment and long-term outcomes of chronic myeloid leukemia patients treated with imatinib as first-line treatment in routine clinical setting from two countries with centralized tyrosine kinase inhibitors (TKIs) treatment. We assessed prognostic significance of European LeukemiaNet (ELN) 2006- and 2009-defined responses and the prognostic value of molecular responses at defined time points on 5-year survivals. Among the cumulative rates of incidence of hematologic, cytogenetic, and molecular responses and all important survival parameters, we evaluated the prognostic significance of different BCR-ABL transcript-level ratios (≤1%; >1%–≤10%; >10%) at 3, 6, 12, and 18 months (n = 199). The ELN optimal response criteria and their predictive role were significantly beneficial for event-free survival at all given time points. We found significant improvement in survivals of patients with BCR-ABL lower than 10% in the 6th and 12th months. Significantly better outcome was found in patients who achieved major molecular response (MMR) in the 12th month. The cumulative incidences of complete cytogenetic response (CCyR) and MMR were significantly associated with the molecular response in the 3rd month. The ELN response criteria and their predictive role were helpful at given time points; however, the 2009 definition did not significantly alter the prognostic accuracy compared with that of the 2006 definition. The significant value was observed for cytogenetic responses at the 6th and 12th month. Moreover, progression-free and event-free survivals were improved with MMR at the 12th month.

The predictive value of early molecular response in chronic myeloid leukaemia patients treated with imatinib in a single real-world medical centre in a developing country

“…(2) In comparison, the percentage of CCyR and MMR among the patients in the present study was 80.0% and 65.7%, respectively, which are comparable to other studies. (15,16) Hence, the results of our study show that a good response can also be achieved in a real-life clinical setting.…”

“…This finding is consistent with the results published by Klamová et al, which showed that patients with a BCR-ABL level < 10% at six months had better survival. (16) Furthermore, Hughes et al also proved that BCR-ABL levels of > 10% at six months and > 1% at 12 months predict inferior EFS and a higher rate of disease progression. (2) This observation is especially important for less developed countries, where the need to use higher dosages of imatinib or the need to change treatment from imatinib to newergeneration TKIs (in order to achieve faster and deeper responses) would result in a significant financial burden.…”

Current survival measures reliably reflect modern sequential treatment in CML: Correlation with prognostic stratifications

“…The observation that achievement of an early response is an important determinant for the outcome in CP‐CML patients treated with first‐line TKIs is not new; several authors have previously shown the importance of early response with respect to OS and progression‐free survival . In this study, our analysis showed that patients who did not achieve CCgR and patients with BCR‐ABL1 transcript levels > 10% at 3 months of imatinib therapy had lower CCI compared with patients who achieved a 3‐month CCgR or patients with BCR‐ABL1 transcript levels ≤ 10% at 3 months, respectively.…”

“…Therefore, cytogenetic examinations at 3 months of imatinib therapy were not available in some patients due to changes in the therapeutic recommendations for CML patients over the last decade. Regarding the analysis of BCR‐ABL1 transcript levels at 3 months, the BCR‐ABL1 transcripts were evaluated as internationally recommended ; patients with BCR‐ABL1 transcript levels ≤ 10% were compared to those with BCR‐ABL1 transcript levels > 10% . However, the BCR‐ABL1 transcript levels were available only in patients, whose samples were analyzed in three laboratories with the standardized quantitative real‐time RT‐PCR methodology at the time of data collection (annual quality control was provided by the National reference laboratory for DNA diagnostics in the Czech Republic).…”

“…In this study, we analyzed for the first time the impact of the internationally recognized prognostic scores, the Sokal , the Euro , and the EUTOS risk scores , as well as the achievement of CCgR at 3 months of imatinib therapy on the CCI, the CLFS, and the overall survival (OS) using the data of all consecutive Czech and Slovak CML patients in chronic phase (CP‐CML) who received first‐line imatinib in the period 2000–2011. In addition, we evaluated the current survival measures and the OS with respect to the BCR‐ABL1 transcript levels at 3 months of imatinib therapy—a stratification that has been recently applied in several studies .…”