The primary endpoint was OS as determined by the Kaplan Meier method.4 OS was defined as time from initiation of ibrutinib to death. Comparisons of survival were made using COX regression analyses.5,6 All other comparison analyses were descriptive. Early deaths were defined as a death from any cause occurring within 12 months of ibrutinib treatment initiation. Secondary endpoints included response rates, progression-free survival (PFS), discontinuation rates, and reasons for discontinuation. PFS was defined as time from ibrutinib initiation to progression or death from any cause. Patients were otherwise censored at the time of last follow‐up. Statistical analyses were performed using STATA 10.1 (Stata Statistical Software: Release 10, 2007; StataCorp LP, College Station, TX). All tests were two‐sided at the 5% level.
Of the 391 patients identified, 59% were 65 years or older (≥65 YO). The median age at initiation of ibrutinib was 63 years (range 36–96). Patient characteristics are detailed in Table 1. Poor risk prognostic features were similar in patients stratified by age at start of ibrutinib (≥65 YO and <65 YO cohorts, respectively): del 17p (29%, 30%), TP53 mutation (21%, 19%), IGHV unmutated (71%, 64%), and complex karyotype (25%, 21%).
The median time from diagnosis to initiation of ibrutinib was 35 months for patients ≥65 YO and 25 months for those <65 YO. Eleven percent of older patients were initiated on a lower than standard dose of ibrutinib (420 mg daily) in contrast to 2% of younger patients (p=0.02). In older patients, 20% required dose reduction compared to 13% of younger patients (p=0.07). Dose interruptions occurred in 46% of older and 36% of younger patients (p=0.04); the median duration of dose interruption was 13 and 10 days, respectively (p=0.49). Ibrutinib discontinuation occurred in similar frequency for older and younger patients (25%, 22%). Intolerance was the most common reason for discontinuation in both age groups (n= 36 and 20, respectively), followed by CLL progression (n= 6, 6), and Richter’s transformation (n= 5, 4).
Investigator assessed overall and complete response rates for ibrutinib were 79% and 15% in patients ≥65 YO and 85% and 20% in those <65 YO. There was no difference in PFS based on age (HR 1.13, p =0.69), Figure 1. At a median follow up of 13.8 months (range 1–76 months), a total of 26 deaths were observed. There was a higher proportion of deaths in the older cohort (8.7% vs 3.8%, 20 deaths vs 6 deaths), though difference in OS did not reach statistical significance (HR 2.1, p=0.097). Figure 1. The number of early deaths, defined as occurring within the first 12 months of therapy, was 13 in patients ≥65 YO compared to 4 in patients <65 YO, p=0.3.
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