Safety and Efficacy Of Imatinib In Elderly Patients With Chronic-Phase Chronic Myeloid Leukemia: Analysis Of Outcome For < 60 Years Versus ≥ 60 Years

Since the introduction of imatinib (IM), it has been used as a standard frontline therapy for newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML). Its efficacy and durable response have been proved by several clinical studies. However, several prior studies suggested that there may be differences of clinical outcomes according to age groups, and the effect of age on clinical outcomes remains uncertain. The purpose of this study was to evaluate the safety and efficacy of IM in elderly patients by the comparison between age groups (younger patients < 60 years vs. elderly patients ≥ 60 years).

Between January 2001 and March 2013, 798 patients with newly diagnosed CP CML were analyzed. They started IM therapy without prior treatment for leukemia except for hydroxyurea or anagrelide within 6 months of diagnosis. Routine chromosomal analyses were performed using standard banding techniques with bone marrow aspirates and molecular responses were monitored using qRT-PCR assay with 3 month intervals, and then 6 month intervals after achieving major molecular response (MMR). The main end points of this study included the comparisons of IM intolerance, response for IM therapy and survival between two age groups.

A total of 798 newly diagnosed CP CML patients (including 476 men and 322 women) were analyzed. The patients were divided into the following two age subgroups: younger patients < 60 years (n = 698) vs. elderly patients ≥ 60 years (n = 100). Median age was 38 years (range, 5-59) and 66 years (range, 60-86) for each group. In the characteristics for each age group, older age group had a higher Sokal risk score (P< 0.001) and EURO score (P< 0.001). In contrast, EUTOS score was similar (P = 0.157). IM treatment duration of younger and elderly patients were 37.7 and 22.5 months, respectively (P<0.001). Discontinuation of IM due to intolerance occurred in 20.0% and 12.2% for each groups with a higher incidence in elderly patients (P =0.030). At 6 months, 39 (39.0%) of 100 elderly patients (≥ 60 years) achieved complete cytogenetic response (CCyR). Of patients with < 60 years, 370 patients (53.0%) showed CCyR, which was statistically higher than those of elderly patients (P = 0.009). At 12 months, patients with < 60 years showed a higher CCyR rate (66.9% vs. 51.0%, P = 0.002), whereas and there was no difference in MMR rate (23.2% vs. 23.0%, P = 0.963). The 18-month MMR rate was also not different between two age groups (32.2% vs. 28%, P = 0.516). Overall responses of younger patients were more favorable than those of elderly patients (complete hematologic response [CHR] rate, 86.0% vs. 73.0%, P=0.001; CCyR rate, 78.4% vs. 60.0%, P<0.001; MMR rate, 60.0% vs. 45.0%, P=0.004).

The incidence of IM intolerance was higher in elderly patients and IM treatment duration of elderly patients was significantly shorter than it of younger patients. The elderly patients showed low CHR, CCyR and MMR compared with younger patients. Accordingly, an effective treatment strategy with tolerable side effect profiles for elderly patients should be considered. For these reasons, upfront use of second-generation TKIs in elderly patients may be beneficial.

No relevant conflicts of interest to declare.