RESUMO
Background: Imatinib is the most widely used tyrosine kinase inhibitor (TKI) in patients with newly diagnosed chronic-phase chronic myeloid leukemia(CML-CP). However, failure to achieve optimal response after imatinib administration, and subsequent switch to second-generation TKI therapy results in poor efficacy and induces drug resistance. In the present study, we developed and validated a nomogram to predict the efficacy of imatinib in the treatment of patients newly diagnosed with CML-CP in order to help clinicians truly select patients who need 2nd generation TKI during initial therapy and to supplement the risk score system. Methods: We retrospectively analyzed 156 patients newly diagnosed with CML-CP who met the inclusion criteria and were treated with imatinib at the Second Affiliated Hospital of Xi'an Jiao Tong University from January 2012 to June 2022. The patients were divided into a poor-response cohort (N = 60)and an optimal-response cohort (N = 43) based on whether they achieved major molecular remission (MMR) after 12 months of imatinib treatment. Using univariate and multivariate logistic regression analyses, we developed a chronic myeloid leukemia imatinib-poor treatment (CML-IMP) prognostic model using a nomogram considering characteristics like age, sex, HBG, splenic size, and ALP. The CML-IMP model was internally validated and compared with Sokal, Euro, EUTOS, and ELTS scores. Results: The area under the curve of the receiver operator characteristic curve (AUC)of 0.851 (95% CI 0.778-0.925) indicated satisfactory discriminatory ability of the nomogram. The calibration plot shows good consistency between the predicted and actual observations. The net reclassification index (NRI), continuous NRI value, and the integrated discrimination improvement (IDI) showed that the nomogram exhibited superior predictive performance compared to the Sokal, EUTOS, Euro, and ELTS scores (P < 0.05). In addition, the clinical decision curve analysis (DCA) showed that the nomogram was useful for clinical decision-making. In predicting treatment response, only Sokal and CML-IMP risk stratification can effectively predict the cumulative acquisition rates of CCyR, MMR, and DMR (P<0.05). Conclusion: We constructed a nomogram that can be effectively used to predict the efficacy of imatinib in patients with newly diagnosed CML-CP based on a single center, 10-year retrospective cohort study.
RESUMO
This study investigated changes in treatment modalities and outcomes of chronic myeloid leukemia in the chronic phase (CP-CML) after the approval of second-generation tyrosine kinase inhibitors (2G-TKIs) for first-line therapy. Patients were grouped into those who underwent TKI therapy up to December 2010 (imatinib era group, n = 185) and after January 2011 (2G-TKI era group, n = 425). All patients in the imatinib era group were initially treated with imatinib, whereas patients in the 2G-TKI era group were mostly treated with dasatinib (55%) or nilotinib (36%). However, outcomes including progression-free survival, overall survival, and CML-related death (CRD) did not differ significantly between groups. When stratified by risk scores, the prognostic performance of the ELTS score was superior to that of the Sokal score. Even though both scoring systems predicted CRD in the imatinib era, only the ELTS score predicted CRD in the 2G-TKI era. Notably, the outcome of patients classified as high-risk by ELTS score was more favorable in the 2G-TKI era group than in the imatinib era group. Thus, expanding treatment options may have improved patient outcomes in CP-CML, particularly in patients classified as high-risk by ELTS score.
Assuntos
Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva , Inibidores de Proteínas Quinases , Humanos , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Masculino , Pessoa de Meia-Idade , Feminino , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Idoso , Adulto , Mesilato de Imatinib/uso terapêutico , Resultado do Tratamento , Dasatinibe/uso terapêutico , Idoso de 80 Anos ou mais , Pirimidinas/uso terapêutico , Adolescente , Adulto Jovem , PrognósticoRESUMO
The European Treatment and Outcome Study (EUTOS) long-term survival (ELTS) score predicts disease-specific death in patients with chronic myeloid leukemia (CML) being treated with imatinib during the chronic phase (CP) of the disease. However, it is unclear whether the ELTS score predicts CML-related events or treatment responses. This study evaluated the predictive value of the ELTS score regarding prognosis and treatment response in patients with CML-CP. Clinical data were retrospectively obtained from patients enrolled in the CML Cooperative Study Group (CML-CSG), which included patients diagnosed with CML-CP from April 2001 to January 2016, and treated with any tyrosine kinase inhibitor (TKI) as first-line therapy. Among 342 eligible patients, the ELTS scores indicated low-, intermediate-, and high-risk in 74%, 21%, and 5% of patients, respectively. Patients with high ELTS scores had significantly higher disease-specific mortality and worse event-free survival, progression-free survival, and overall survival. Among four risk scores, including the Sokal, Hasford, EUTOS, and ELTS scores, risk stratification by the ELTS score had the highest predictive value in assessing patient prognosis, and also in treatment responses. In fact, the EUTOS and ELTS scores were able to predict the major molecular response within 12 months. Most importantly, the ELTS score was the only scoring system that predicted deep molecular response at any time, regardless of risk level (65.0%, 43.7%, and 23.5% in low-, intermediate-, and high-risk groups, respectively). Compared to other risk scores, the ELTS score was the most sensitive risk classification tool for the four endpoints of interest in this study, as well as molecular responses in patients with CML-CP.