A new risk assessment score more accurately reflects the probability of dying from chronic myeloid leukemia than do existing scoring systems.
A new risk assessment score more accurately reflects the probability of dying from chronic myeloid leukemia (CML) than do existing scoring systems, according to a new study.
The use of tyrosine kinase inhibitors beginning with imatinib has yielded dramatically improved prognosis for CML patients, with an 8-year overall survival (OS) probability of over 80%. “A consequence of the improved survival induced by imatinib is the increased probability of dying of causes other than CML,” wrote study authors led by Markus Pfirrmann, PhD, of Ludwig-Maximilians UniversitÃ¤t in Munich, Germany. “Investigators wonder to what extent survival probabilities still depend on CML.”
The new study included 2,290 patients from several European study cohorts. All patients had BCR-ABL1–positive CML in chronic phase, and received imatinib within 6 months of diagnosis. The results were published online ahead of print in Leukemia.
The median follow-up period was 6.3 years, and the full cohort had an 8-year OS probability of 89%. A total of 208 patients (9%) died during follow-up; the cause of death was CML (defined as death after disease progression) in 92 cases (44% of deaths), non-CML-related in 104 patients (50%), and unknown in 12 cases (6%). The 8-year cumulative incidence probability of CML-related death was 4%, and of non-CML-related death was 7%.
Of those who died of non-CML causes, 50 died of a second cancer, 21 due to a cardiovascular event, 12 due to an infection, and 21 from other causes.
The researchers examined how well existing scoring systems predicted death and its causes; the Sokal, Euro, and EUTOS scores all identified a high-risk group with a significantly higher incidence of CML-related death than other patients. But neither the Sokal nor the Euro score showed any difference between low- and intermediate-risk groups; the EUTOS score did show a difference.
They then created a new scoring system using variables found to be significantly associated with a higher risk of dying of CML: higher age, bigger spleen size below costal margin, higher percentage of peripheral blasts, and low platelet counts. The EUTOS Long-Term Survival (ELTS) score was then validated in 1,120 other patients.
Of that cohort, 61% were considered low risk. The intermediate-risk patients had an increased risk of dying of CML compared to the low-risk group (subdistribution hazard ratio [HR], 2.040 [95% confidence interval (CI), 1.039–4.005]; P = .035). The high-risk group had a subdistribution HR for death from CML of 6.746 (95% CI, 3.614–12.592; P < .001).
This is the first long-term scoring system that considered specifically CML-related death, the authors wrote. “We hope that the ELTS score will be considered for the risk-stratified planning, analysis, and outcome interpretation of clinical trials,” they wrote. “It provides a sound basis for the development of risk-adapted treatment.”