Prognostic significance of additional chromosomal abnormalities at the time of diagnosis in patients with chronic myeloid leukemia treated with frontline tyrosine kinase inhibitors

Abstract

Additional cytogenetic abnormalities (ACA) are considered a high risk feature in chronic myeloid leukemia (CML). However, its prognostic significance at the time of diagnosis in the setting of new tyrosine kinase inhibitors (TKIs) is less well understood. Patients with CML in CP with or without ACA at diagnosis treated with frontline TKIs in prospective clinical trials were analyzed for outcomes. Among 603 patients treated, 29 (5%) had ACA. Patients with ACA included 2 of 72 (2.8%) treated with imatinib 400 mg, 9 of 207 (4.3%) with imatinib 800 mg, 10 of 148 (6.7%) with dasatinib, 6 of 126 (4.7%) with nilotinib, and 2 of 50 (4%) with ponatinib. There was a significantly higher rate of complete cytogenetic response (CCyR) at 6 months in patients without ACA (P = .02). However cumulative CCyR and major molecular response (MMR) rates were not different. Similarly, MR4.0 and MR4.5 rates were similar for both groups; two CML-ACA patients maintained MR 4.5 for at least 2 years. At 5 years, ACA at diagnosis did not significantly impact transformation-free, failure-free, event-free, or overall survival expectations. Acknowledging small sample size estimates, response rates and survival outcomes were comparable in CP with ACA irrespective of whether chromosomal abnormalities were "major route" or other. The presence of ACA at diagnosis does not confer worse prognosis for patients with CML treated with TKI. Thus, the presence of ACA at diagnosis should not alter treatment strategies in these patients.

FIGURE 1

(A) Clonal chromosomal abnormalities at diagnosis. (B) Chromosomal abnormalities according to classification by Wang et al. Foot note: ^{^}- ≥ 2 ACAs: (+8,-Y,der(5)t=> N = 1); (+der(22)t,−7,t(1:13)=> N = 1); (+der (22)t + other rare chromosomal=> N = 4); (+19,+21: N = 1)]

FIGURE 2

Overall survival according to the presence (N = 29) or absence (N = 574) of ACA at the time of diagnosis. Sixty nine and five deaths occurred in the CML-CP and CML-CE cohorts, respectively. Abbreviations used: NR-not reached, OS-overall survival