Event-Free Survival According to Age in Patients with Chronic Myeloid Leukemia Receiving Imatinib Frontline: The Younger, the Later, the Worse?

Differences in baseline features and follow-up among patients with chronic myeloid leukemia (CML) according to age at diagnosis have been recently reported in cohorts from clinical controlled trials (Castagnetti F et al, 2015). To evaluate this issue in a real-life setting, we revised 207 consecutive CML patients treated at our Institution with imatinib frontline from 6/2002 to 6/2013, dividing them in young adults (>20 <45 years) (YA), middle-aged adults (≥45 <65 years) (MA) and elderly (≥65 years) (EL). The main features at baseline of the whole cohort and of the 3 age groups are reported in the Table.

	ALL	YA	MA	EL	p
N° of patients	207	61	72	74
M/F	108/89	30/31	40/32	38/36	0.752
Median WBC (x 109/l) IQR	66.1 (32.7 – 119.0)	109.8 (65.9 – 148.0)	59.5 (31.3 – 126.6)	40.1 (26.5 – 81.4)	<0.001
Median Hb (g/dl) (IQR)	12.5 (11.0 – 13.5)	11.7 (9.8 – 12.7)	12.7 (11.0 – 14.2)	12.8 (11.3 – 13.7)	0.002
Median PLT (x 109/l) IQR	414 (275 – 616)	445 (291 – 597)	378 (262 – 546)	457 (271 – 732)	0.287
Spleen enlargement (>5cm)  N° (%)	17 (8.3)	11 (18.3)	4 (5.6)	2 (2.7)	0.003
Sokal score (N°) Low/Int/High	89/93/20	47/9/3	38/27/5	4/57/12	<0.001
Comorbidities ≥ 2, N° (%)	77 (37.2)	5 (8.1)	26 (36.1)	46 (62.1)	<0.001

The rates of complete cytogenetic response (CCyR) were similar (86.4% in YA, 95.5% in MA and 91.0% in EL, p=0.227) while the rate of major molecular response was higher in the MA group (89.7% vs 63.8% in YA and 75.8% in EL, p=0.001). The number of events (permanent discontinuation due to toxicity, primary or secondary resistance, any death for CML related or unrelated causes) was lower in the MA group [8 (11.1%) vs 21 (34.4%) in YA and 28 (37.8%) in EL, p=0.001]: no difference was observed in the rate of evolution to blastic phase [3 (4.9%) in YA, 1 (1.4%) in MA and 2 (2.7%) in EL, p=0.478]. The number of deaths was higher in the EL group [12 (16.2%) vs 2 (3.2%) in YA and 0 in MA, p<0.001]: it is worth of note, however, that 11/12 deaths in the EL group were not related to CML progression. The 4-year event-free survival (EFS) for the whole cohort was 73.5% (95%CI 67.0 – 80.0): the 4-year EFS in the MA group [92.0% (95%CI 85.1 – 98.9)] was significantly higher than in YA group [67.3% (95%CI 55.1 – 79.5)] and in EL group [61.1% (95%CI 49.5 – 73.7)] (p=0.001). The 4-year overall survival (OS) for the whole cohort was 94.4% (95%CI 90.9 – 97.9): the 4-year OS in the EL group [72.4.% (95%CI 56.9 – 87.9)] was significantly lower than in YA group [96.3% (95%CI 91.2 – 100)] and in MA group (100%) (p<0.001). In conclusion, age at diagnosis influences significantly the course of CML patients treated with imatinib: the MA group  has the best follow-up with an excellent OS and EFS, while the relatively lower OS and EFS in the EL group are clearly related to the incidence of unrelated deaths like in the general aged population. A possible explanation of the counterintuitive worse course of YA group is the delayed diagnosis in these patients (higher WBC counts, lower Hb levels, higher rate of spleen enlargement > 5 cm) compared to aged patients, who have often concomitant diseases and make routinely blood analyses: however, a more aggressive biology of CML in YA could not be excluded and warrants further investigations.