Is EUTOS Score Predictive Of Outcome In Patients With Early Chronic Phase Chronic Myeloid Leukemia Treated With Imatinib? Preliminary Data From The National Protocol Of The Chilean Cooperative Group Panda

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5196-5196 ◽  
Author(s):  
Javier Zelada ◽  
Marisa Pia Aida Capurro ◽  
Bernardita Rojas ◽  
Lilian M Pilleux ◽  
Augusto Aspillaga ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Predictive Value ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Cooperative Group ◽  
Line Treatment ◽  
First Line ◽  
Eutos Score ◽  
First Line Treatment

Abstract Background Before the Tirosine Kinase Inhibitors (TKI) era, the SOKAL and HASFORD scores have been used to predict outcome in chronic myeloid leukemia (CML) patients. The recently reported European Treatment and Outcome Study (EUTOS) score is a simple formula created to identify patients with significantly lower probabilities of responding to therapy and survival. The MD Anderson group didn´t validate this score. Aims To validate the EUTOS score in our population treated in the public health hospitals in Chile with a single protocol of the cooperative group PANDA. Methods Patients were selected from the data base of the CML 2007 PANDA protocol. All patients were adults (>15 years old) in early chronic phase and received first-line treatment with imatinib-based regimes and had a minimal follow up of twelve months. Event was defined as not reaching complete cytogenetic response in the first year of treatment, death from any cause at any time, loss of complete hematologic response, loss of major cytogenetic response, or progression to accelerated or blast phase. Overall survival (OS) was defined as death of any cause at any time. Event free survival (EFS) was defined as time from diagnosis to any event. Results A total of 78 patients were selected from the 330 patients of the data base. The rest had incomplete data. The median age was 48 (range 16 to 79 years old), 47 men and 31 women. Patients with low EUTOS score were 49 (63%) and 29 (37%) were high. The sensitivity of EUTOS was 46% , the specificity was 71% and the negative predictive value was 68%. There was no significative difference in EFS and OS in both EUTOS groups. Conclusions EUTOS score was not predictive of outcome in our patient population. Nevertheless it showed a good negative predictive value meaning that it can only identify low risk patients. This could be used in developing countries to select patients that could use lower cost TKI in first line treatment. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Clinical Relevance of Failure to Achieve Early Molecular Response in Chronic Myeloid Leukemia in Chronic Phase

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5160-5160
Author(s):  
Ji Yun Lee ◽  
Sung Hee Lim ◽  
Hae Su Kim ◽  
Kwai Han Yoo ◽  
Haa-Na Song ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Clinical Outcomes ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Molecular Response ◽  
Line Treatment ◽  
First Line ◽  
Transcript Levels ◽  
Significant Difference ◽  
First Line Treatment

Abstract Purpose The early molecular response (EMR, ≤ 10% BCR-ABL1 at 3 months) of tyrosine kinase inhibitor (TKI) treatment for patients with chronic myeloid leukemia (CML) in chronic phase (CP) has been reported to have strong correlation with long-term outcome. We aim to investigate the prognostic interaction of the EMR and major molecular response (MMR). Methods We retrospectively reviewed data for a total of 165 patients with newly diagnosed CML-CP who received TKIs (imatinib, nilotinib, or dasatinib) as first-line treatment between January 2003 and April 2013. Of the total 128 patients who were regularly monitored by peripheral blood molecular analysis, 85 had a BCR-ABL1 assessment at 3 months and were finally included in the analysis. Results The median age of all patients was 49 years and 87.1% received imatinib as first line treatment. High risk group by Sokal and EUTOS were 29.4% and 14.1%, respectively. Patients with EMR (n = 56, 65.9%) had a tendency to have low risk disease and to be treated with 2nd generation of TKIs. With a median follow-up duration of 53.6 months (range, 5.4-131.3), the 5-year OS, 5-year FFS, and 5-year EFS were 92.5%, 74.8%, and 68.0%, respectively. Median time to achieve MMR was 11.1 months (95%CI, 8.4 - 13.8). The outcomes at 5 year comparing patients whose BCR-ABL1 transcript levels ≤ 10% vs >10% at 3 months were as follows: OS, 92.2% (95% CI 84.9-99.1) vs 92.8% (95% CI 83.7-102.3), p = 0.819; FFS, 84.7% (95% CI, 75.6-94.4) vs 57.4% (95% CI, 39.0-75.0), p < 0.001; and EFS, 73.6% (95% CI 62.5-85.5) vs 57.8% (95% CI 40.0-76.0), p = 0.050. Six (10.7%) of 56 patients with BCR-ABL1 transcript levels ≤ 10% at 3 months failed to achieved an MMR and 18 (62.1%) of 29 patients with > 10% at 3 months achieved an MMR. Based on these heterogeneous clinical outcomes, we further explored subgroup analysis according to the achievement of MMR for refined discrimination of survival outcomes. There was no significant difference of clinical outcomes between ≤ 10% vs > 10% at 3 months among the patients who achieved MMR (OS, p = 0.376; FFS, p = 0.793; and EFS, p = 0.266). In patients who did not achieved MMR, only FFS was significantly difference between ≤ 10% vs > 10% at 3 months (OS, p = 0.489; FFS, p = 0.014; and EFS, p = 0.199). Conclusion Patients who failed to achieve EMR but finally reached MMR have excellent prognosis that whether we have to change TKI for EMR failure is to be addressed by ongoing prospective clinical trials. Disclosures Jang: Alexion Pharmaceuticals: Research Funding.

scholarly journals The Role of the Newer Tyrosine Kinase Inhibitors As First Line Treatment in Chronic Phase Chronic Myeloid Leukemia – an Updated Meta-Analysis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4563-4563
Author(s):  
Ronit Gurion ◽  
Liat Vidal ◽  
Avi Leader ◽  
Pia Raanani ◽  
Anat Gafter-Gvili
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Meta Analysis ◽  
Chronic Phase ◽  
Molecular Response ◽  
Line Treatment ◽  
First Line ◽  
Time Points ◽  
Grade 3 ◽  
First Line Treatment

Abstract Background: Imatinib, nilotinib and dasatinib are all considered first line treatment in chronic phase (CP) chronic myeloid leukemia (CML) patients. The choice of the most suitable tyrosine kinase inhibitor (TKI) for an individual patient is influenced by multiple factors including disease characteristics, patient comorbidities and preferences, as well as each TKI's unique profile of adverse events. A meta-analysis of second generation TKIs as first line treatment for patients with CML was published by our group in 2011. In view of the recently published long term results of three of the trials included in the previous meta-analysis and data from two new trials, we decided to update our data. Objectives: To evaluate the efficacy and toxicity of different TKIs as first line treatment for patients with CML. Methods: Systematic review and meta-analysis of randomized controlled trials comparing first line treatment with the newer TKIs (nilotinib, dasatinib, bosutinib and ponatinib) to imatinib in patients with CP-CML. The MEDLINE, conference proceedings and references were searched until August 2014. Two reviewers appraised the quality of trials and extracted data. The following outcomes were assessed: complete cytogenetic response (CCyR); major molecular response (MMR); complete molecular response (CMR), defined as a 4.5 log reduction in BCR-ABL transcripts; early molecular response, defined as BCR-ABL transcript levels of 10% or less at 3 months; progression to accelerated phase (AP) / blastic crisis (BC); all-cause mortality (ACM) and toxicity. Relative risks (RR) were estimated and pooled. Random-effect model was used in all analysis. Results: Our search yielded six trials including 2,426 patients. These trials compared the effects of nilotinib, dasatinib, bosutinib or ponatinib to imatinib. Data from the six trials were available for analysis of MMR. Treatment with the newer TKIs significantly improved MMR at all-time points (3, 12, 18, 24 and 48 months) compared to imatinib (Table 1). Of note, the newer TKIs significantly increased the rate of CMR compared to imatinib at 12 months (RR 2.68, 95% CI 1.64-4.36, 5 trials, figure 1) and at 24 months (RR 2.04, 95% CI 1.62-2.57, 3 trials). Moreover, there was a statistically significant advantage in favor of the newer TKIs as compared to imatinib in terms of early molecular response at 3 months (RR 1.34, 95% CI 1.27-1.41, 5 trials). Importantly, progression rate to AP/BC at 24 months was significantly lower with the newer TKIs in comparison with imatinib (RR 0.35, 95% CI 0.20-0.61, 4 trials). However there was no difference in ACM (RR 0.73, 95% CI 0.46-1.15, 4 trials). We conducted a meta-analysis for specific adverse events according to the distinct toxicity profile of the different TKIs. Severe peripheral arterial occlusive disease occurs more frequently in the newer TKIs arm (i.e. nilotinib and ponatinib) (RR 8.13, 95% CI 1.51-43.83, 2 trials) than in the imatinib arm. In addition, pleural effusion requiring discontinuation occurs at a higher rate in the newer TKIs arm (RR 4.61, 95% CI 1.31-16.23, 4 trials; dasatinib and bosutinib vs. imatinib). Regarding hematologic toxicity including grade 3-4 anemia and neutropenia, there was no difference between the two arms (all newer TKIs vs. imatinib). However, regarding thrombocytopenia grade 3-4, there were more events with thrombocytopenia in the newer TKIs arm compared to imatinib (RR 1.41, 95% CI 1.01-1.97). Conclusions: With a longer follow-up of 4 years, the newer TKIs remain more potent than imatinib in terms of MMR, CMR and early molecular response. Yet, an effect on overall survival cannot be shown. Since CMR is a prerequisite for treatment discontinuation, the newer TKIs can potentially facilitate cessation of treatment more frequently than imatinib. These data should be taken into consideration in choosing treatment for a newly diagnosed CML patient. Table 1 – MMR at different time points Time point Relative risk 95% Confidence of interval No. of trials 3 months 6.63 2.31-19.01 5 12 months 1.68 1.48-1.89 6 18 months 1.37 1.18-1.59 4 24 months 1.28 1.06-1.54 4 48 months 1.20 1.05-1.38 3 Figure 1 – CMR at 12 months Figure 1 –. CMR at 12 months Disclosures No relevant conflicts of interest to declare.

A Decade Of Imatinib As First-Line Treatment Of Chronic Myeloid Leukemia: A Single - Latin American Institution Experience

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5194-5194
Author(s):  
Alvaro Cabrera Garcia ◽  
Carolina Balderas Delgado ◽  
Juan Julio Kassack Ipiña ◽  
Christian Omar Ramos Peñafiel ◽  
Juan Collazo Jaloma ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Latin American ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Hematologic Toxicity ◽  
Line Treatment ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Eutos Score

Abstract Targeted therapy commenced against Chronic Myeloid Leukemia (CML) with the development of small-molecule tyrosine kinase inhibitors (TKIs), since its approval in 2001 as first-line therapy, imatinib has been effective in achieving high response rates and improving the prognosis. However, the excellent results of large clinical trials are not entirely reproducible in the “real world”, we want to share our experience of a decade of use as front-line treatment. A total of 160 patients with previously untreated CML since 2002 were reviewed: 90% chronic phase (CP), 7% accelerated phase (AP), and 3% blast phase (BP). All were treated with standard-dose imatinib. In CP, overall survival (OS) at 75 months was 82% and progression-free survival 66%(PFS). Survival was worse in those over 60 years (P= < .001). 40% achieved and maintained Complete Cytogenetic Response (CCyR), 19 patients progressed to BP. 23.4% had some degree of hematologic toxicity that required a temporary suspension or reduction of the initial dose. 26.8% of patients with chronic phase treated at our institution were in the high EUTOS score. In this population, the EUTOS score was not predictive for outcome. Our study showed that imatinib is effective, and well tolerated by our patients and remains as a good strategy used as first-line therapy for patients with CML. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Early cytogenetic and molecular response during first-line treatment of chronic myeloid leukemia in chronic phase

Cancer ◽  
2011 ◽  
Vol 117 (23) ◽  
pp. 5261-5270 ◽  
Author(s):  
Alfonso Quintás-Cardama ◽  
Jorgé E. Cortes ◽  
Hagop M. Kantarjian
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Molecular Response ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

scholarly journals Efficacy and Safety of Generic Dasatinib As First-Line Treatment in Patients with Chronic Myeloid Leukemia in Chronic Phase: Final Analysis with 2-Year Follow-up

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3616-3616
Author(s):  
Jie Jin ◽  
Li Meng ◽  
Wenjuan Yu ◽  
Peng Liu ◽  
Xin Du ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Primary Endpoint ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Line Treatment ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
First Line ◽  
First Line Treatment

Abstract Purpose: Generic dasatinib, a second-generation tyrosine kinase inhibitor (TKI), was approved as a second-line treatment for chronic myeloid leukemia (CML) patients in chronic phase (CP) in china. We initiated a prospective, multi-center and single-arm clinical trial (NCT04925141) from May 2016 to October 2018 to evaluate efficacy and safety of generic dasatinib as first-line treatment in China. The primary endpoint was achieved, here we reported the 2 years follow-up results to see its long-term clinical benefit in Chinese patients. Methods:The study included the newly diagnosed CML-CP patients who was diagnosed by the presence of Philadelphia (Ph) chromosome and/or presence of BCR-ABL fusion gene. Key inclusion criteria were as follows: 1) Age ≥ 18 years; 2) The CML subjects in chronic phase with the Ph+ definitive diagnosis were within 6 months before the onset of administration of the study drug; 3) The ECOG performance grades of 0-2; 4) Sufficient main organ functions. All newly diagnosed patients were given 100mg/d (initial dose) of the generic dasatinib. The primary endpoint was molecular major response (MMR) calculated based on the BCR-ABL1 ≤ 0.1% at the 12th month. Secondary endpoints were proportion of subjects who achieved and maintained MMR at 3, 6, and 18 months; Cumulative MMR rates at 6, 12, and 24 months were determined. All patients were followed up through the hospital outpatient departments at second, fourth and eighth weeks, and third, sixth, ninth, twelfth, eighteenth, and twenty-fourth months. The follow-up ended on December 6, 2019. The SAS 9.2 software was utilized for all statistical analyses in this study, and the two-sided test was performed to see variances. Results: A total of 59 patients were included in this trail, with median age of 44 (19 - 70), and 7% of the subjects were at high risk based on the Sokal index for the disease prognosis. The primary endpoint MMR rate at the 12th month was 80.8% which had been published. At 12 months, the cumulative response rate (CCyR) was 85.5% (47/55) and the cumulative MMR was 76.4% (42/55). Here we are reporting the 2 years follow ups. At 24 months, the complete hematological response (CHR) was 88.4%, the cumulative MMR rate was 73.7%, the cumulative MR4.0 rate was 63.6%, the cumulative MR4.5 rate was 58.2%, and the cumulative complete molecular response (CMR) rate was 58.2%. The most common adverse events (AEs) was thrombocytopenia (42.4%) in hematology and pleural effusion (20.3%) in non-hematology, only 11.9% and 1.7% of whom were grade III~IV respectively. Conclusion: This was the first report on domestic dasatinib as the first-line treatment for CML-CP patients received a clinical benefit with 24 months in China. Safety was similar with that of the original study data. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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