Long-term survival with CML with imatinib or transplantation as first-line treatment: Comparison of outcomes from CML studies IIIA and IV

Abstract

With introduction of the tyrosine kinase inhibitor (TKI) imatinib, the treatment strategy of CML has profoundly changed. TKIs became the first-line treatment of choice for CML competing with allogeneic hematopoietic stem cell transplantation (HCT). Variables to be considered in choosing TKIs for first-line therapy are as follows: conventional risk score; cytogenetic findings with major- route additional chromosomal aberrations (ACA) at diagnosis, and high-risk ACA in the course of CML; comorbidities; treatment costs. In cases of refractoriness to imatinib, the 2nd line treatment options are: clinical response milestones; adherence to therapy; resistance mutations; clonal evolution; therapy intolerance; drug safety; health care setting. CML Study IV, a randomized treatment study concerning imatinib dose optimization and combined therapy with imatinib and cytarabine or interferon α included 1551 newly diagnosed patients in chronic phase. The key outcome was no superiority of survival of any treatment option. Imatinib 400 mg provides close to normal life expectancy in chronic-phase CML patients. Survival is independent of time to response. Outcome of CML is currently more determined by disease and patients’ factors, e.g., comorbidities and smoking, and by center effects than by initial treatment selection. A comparison of long-term survival after HCT or imatinib treatment showed that low risk patients had similar survival with both options. Attempts at improving treatment should focus on subgroups of refractory disease e.g. by HCT, and on non-CML determinants of survival. Aft er progression to blast crisis, HCT did not provide a significant survival advantage, although a special study showed that most long-term survivors (72%) were patients who received a transplant. The 10-year deep molecular remission rates of 70%-80% indicate that the majority of imatinib-treated patients are candidates for treatment discontinuation.