General AML

The prognostic impact of CD25 expression in elderly AML patients treated with plerixafor and decitabine

CD25 (interleukin-2 receptor α [IL2Ra]) has been reported to be expressed on leukemic blasts and is a marker for chemotherapy resistant Leukemic Stem Cells (LSCs). Additionally, previous reports have shown that CD25 expression on Acute Myeloid Leukemia (AML) blasts correlates with poor survival outcomes in younger AML patients.2 However, the prognostic impact of CD25 expression in older AML patients treated with hypomethylating agents is not yet elucidated, hence the rationale for this study.

Allan et al., from Weill Cornell Medicine, New York, retrospectively analyzed the impact of baseline CD25 expression on the clinical outcomes of elderly newly diagnosed AML patients who were enrolled in a phase I/II study (NCT01352650), which combined plerixafor (CXCR4 antagonist) and decitabine. The results of the study were published in Leukemia & Lymphoma on 20th July 2017.1

Overall, Day 0 (D0) Bone Marrow (BM) samples from 58 de novo AML patients (median age = 73 years) were retrospectively assessed for baseline CD25 expression on leukemic blasts using flow cytometry. Based on the flow cytometry analysis, 34.5% (20/58) and 65.5% (38/58) were CD25 positive (CD25pos) and CD25 negative (CD25neg), respectively.

The key results of the study were:
  • There was a significant increase in baseline BM CD25 expression in patients who had a survival ≤1 year (P = 0.02) or in patients who were resistant to therapy (P = 0.033)
  • Median Overall Survival (OS) in CD25pos and CD25neg patients; 6.3 vs 11.5 months, P = 0.002
  • Median OS in CD25pos and CD25neg intermediate risk patients were 5.3 and 13.4 months, respectively; P = 0.003
  • CD25 expression was not an independent predictor for OS; HR = 2.02, P = 0.03
  • Mutations in ASXL1 (HR = 2.47, P = 0.030) and TET2 (HR = 2.30, P = 0.020) were found to independently predict OS

The authors concluded by noting that “CD25 expression identifies patients at risk for resistance to hypomethylating chemotherapy but does not independently predict OS in an older AML population treated with decitabine and plerixafor”.

Abstract

We investigated CD25 expression in older (≥60 years) patients with new acute myelogenous leukemia treated with decitabine and plerixafor. Patients resistant to therapy or survival ≤1 year had significantly higher percentages of CD25pos myeloid blasts in baseline bone marrow. CD25pos patients had an increased odds of resistance compared to CD25neg patients (p = .015). In univariate analysis, we found CD25pos patients had inferior survival compared to CD25neg (p = .002). In patients with intermediate risk cytogenetics, CD25pos status stratified patients associating with inferior survival (p = .002). In multivariable analysis, CD25 and TP53 mutations trended towards predicting remission to therapy but were not predictive of survival. Only remission status, ASXL1 and TET2 mutations were found to independently predict overall survival (OS). We conclude CD25 expression identifies patients at risk for resistance to hypomethylating chemotherapy but does not independently predict OS in an older AML population treated with decitabine and plerixafor.

References
  1. Allan J.N. et al. CD25 expression and outcomes in older patients with acute myelogenous leukemia treated with plerixafor and decitabine. Leuk Lymphoma. 2017 Jul 18: 1–8. DOI: 10.1080/10428194.2017.1352089. [Epub ahead of print].
  2. Gönen M. et al. CD25 expression status improves prognostic risk classification in AML independent of established biomarkers: ECOG phase 3 trial, E1900. Blood. 2012 Sep 13; 120(11): 2297–2306. DOI: 10.1182/blood-2012-02-414425. Epub 2012 Aug 1.