Survival outcomes in chronic myeloid leukemia (CML) treated with imatinib as monotherapy are high and are not necessarily influenced by faster responses or disease-related factors, with outcomes more associated with comorbidities and external factors, according to 10-year survival outcomes from a randomized study.
“Imatinib 400 mg provides close to normal life expectancy,” said Ruediger Hehlmann, MD, a professor of medicine at the Mannheim Medical Faculty of the University of Heidelberg and coordinator of the German CML study group, in Heidelberg, Germany. He was presenting findings from the CML-Study IV here at the European Hematology Association (EHA) 2017 Congress.
“Survival is independent of time to response,” he said. “Outcomes of CML are currently more determined by patients’ and disease factors, such as comorbidities and smoking, and by microeconomic elements, such as treatment center, than by initial treatment selection.”
CML-Study IV was a randomized, five-group treatment optimization study conducted at 210 centers in Germany, Switzerland, and the Czech Republic. The 1551 patients had newly diagnosed CML in chronic phase and were recruited between July 2002 and March 2012.
Of the patients in the current analysis, 1536 had evaluable data, included 400 patients treated with imatinib 400 mg, 430 patients treated with imatinib plus interferon, and 420 patients treated with imatinib 800 mg. Recruitment in two other groups — imatinib plus cytarabine (n = 158) and imatinib after interferon failure (n = 128) — was halted after a pilot phase.
The median patient age was 53 years, and 61% of patients were male.
With a median observation time of 9.5 years, the study showed an overall survival rate of all patients of 82%, 10-year progression-free survival of 80%, and a relative survival rate of 92% (compared with 92% in the general population).
The 10-year overall survival rates did not differ significantly between groups, with rates of 80% with imatinib 400 mg, 84% with imatinib plus interferon, 79% for imatinib 800 mg, 84% for imatinib plus cytarabine, and 79% for imatinib after interferon.
Patients reaching the molecular response milestones at 3, 6, and 12 months had a significantly better survival, the researchers report: Patients who achieved responses of BCR-ABL on the international scale of less than 1% between 4.5 and 7.5 months (n = 594) had a somewhat higher 8-year overall survival rate (93%) compared with those who had a response greater than 1% in the same time period (n = 385 [86%]), they add.
However, the higher (800-mg) dose of imatinib, which has shown faster responses in previous research, did not show a detectable survival advantage, the researchers reported.
“Considering the previously published data showing earlier and deeper molecular responses in imatinib 800 mg, the expectation would be that survival with [the higher dose] should be better, but the message from this study is that the earlier response did not translate to better survival,” Dr Hehlmann said.