Interleukin 2 Receptor-α (CD25) Expression Is Associated with Shortened Overall Survival and Resistance to Induction Therapy with Plerixafor and Decitabine in Older Patients with Newly Diagnosed Acute Myeloid Leukemia (AML)

Introduction: Interleukin 2 receptor-α (CD25) expression on myeloid leukemic blasts may be a marker for chemotherapy-resistant leukemia stem cells (Saito et al. , 2010) and has been associated with poor overall survival (OS) in AML patients (pts) 60 years enrolled in a Phase I clinical trial combining the CXCR4 antagonist, plerixafor and the DNA methyltransferase inhibitor, decitabine (Roboz et al. , 2013). Methods: BM aspirates were available for 69 newly diagnosed older AML pts treated with 1-4 cycles of 5 days of plerixafor combined with 10 days of decitabine. Pts with favorable risk cytogenetic or mutational profiles were excluded from the clinical trial. Multi-parameter flow cytometry was used to evaluate the expression of CD25 in blast and progenitor (CD34+) populations. Cells were gated on CD45dim/SSClo characteristics. Pts were considered positive (CD25+) when greater than 10% of the gated population expressed CD25. Results: Of 69 pts, 58 were evaluable for survival and 57 for response; one pt died prior to scheduled response assessment. Of 58 pts evaluated at baseline (pre-treatment BM), 20 (34.5%) were CD25+ vs. 38 (65.5%) CD25-negative (CD25-). CD25+ pts had significantly inferior median OS (152 days vs. 419 days, p=0.003) and were at higher risk of dying within 1 year of diagnosis, relative risk (RR) 1.58 (95% 1.04-2.41). Similarly, pts surviving less than 1 year had significantly higher percentages of CD34+ cells expressing CD25 than those who lived greater than 1 year (7.82% vs. 4.77%, p=0.028). CD25+ pts were less likely to respond to therapy, RR 1.90 (95% CI 1.23-2.93) and, in turn, pts who were resistant to therapy had higher baseline CD25 expression level than those who responded (7.82% vs. 4.87%, p=0.033). Five CD25+ pts (25%) and 12 CD25- pts (32%) received an allogeneic transplant. Transplanted CD25+ pts had improved OS vs. CD25+ pts without transplant, (median OS not reached (NR) vs. 107 days), p=0.005. In contrast, there was no significant difference in survival between CD25- pts with and without allogeneic transplant, p=0.96. Also, there was no difference in median OS between CD25+ pts receiving transplant vs. CD25- pts (median OS NR vs. 419 days), p<0.40. There was no difference in survival between CD25+ pts with intermediate risk cytogenetics vs. CD25+ pts with unfavorable cytogenetics (OS 153 vs. 172, p=0.77). Lastly, CD25+ pts had significantly worse OS compared to CD25- pts with unfavorable cytogenetics, (median OS 152 vs. 333 days) respectively, p=0.05. Compared to CD25- pts, CD25+ pts were older (median age 74.5 vs. 71.5, p=0.096), more likely to be male (75% vs. 47.3%, p=0.055) and had higher baseline WBC (19x1000/uL vs. 5x1000/uL, p=0.089) and pretreatment lactate dehydrogenase (LDH) (median 365 vs. 271, p=0.04). Analysis of diagnosis BM blast percentage yielded no difference between CD25+ and CD25- pts (62% and 46%, p=0.44). Sixteen (80%) and 4 (20%) of CD25+ patients had intermediate and unfavorable cytogenetics vs. 21 (55%) and 17 (44%) CD25- pts respectively, p=0.09. No significant difference between groups was noted when evaluating the mutational status of TET2, TP53, RUNX1, DNMT3A, NPM1, or FLT3 . Conclusions: Interleukin 2 Receptor-α expression on leukemic blasts is known to correlate with poor prognosis and OS in young pts with AML who have been treated with cytotoxic chemotherapy. We have demonstrated that >10% CD25 expression on CD34+ blasts is associated with poor OS and resistance to therapy in AML pts > 60years of age treated with the combination of plerixafor and decitabine. Pts with >10% CD25 expression on CD34+ cells were at increased risk of death within one year and increased risk of resistance to induction therapy. Thirty-four percent of the pts in this study were CD25+, consistent with previous reports (Terwijn et al. , 2009). This study highlights the importance of CD25 expression on CD34+ leukemic cells in determining prognosis, OS, response to hypomethylating agent therapy and benefit of transplant in older pts with newly diagnosed AML. Further investigations into the aggressive nature of CD25+ AML, mechanisms of resistance and novel therapeutics are ongoing. Disclosures Roboz: Teva Oncology: Consultancy; Novartis: Consultancy; Sunesis: Consultancy; Astra Zeneca: Consultancy; Glaxo SmithKline: Consultancy; Celgene: Consultancy; Agios: Consultancy; Novartis: Consultancy; Astex: Consultancy. Ritchie: Celgene, Incyte: Speakers Bureau.