A Pilot Trial of Lirilumab With or Without Azacitidine for Patients With Myelodysplastic Syndrome

We report the results of a prospective trial of lirilumab in patients with myelodysplastic syndrome (MDS). A total of 10 patients were included. Higher-risk patients received lirilumab with azacitidine, lower-risk patients received single-agent lirilumab. Two patients achieved complete remission (CR) and 5 achieved marrow CR. Although the small sample size precludes definitive conclusions, the results of this study indicate the efficacy and safety of lirilumab in patients with MDS. Background: Enhancement of natural killer cell activity by blocking interactions between killer immunoglobulin (Ig)-like receptors (KIRs) and human leukocyte antigen-C (HLA-C) molecules can improve outcomes in myeloid malignancies. Lirilumab is a human IgG4 monoclonal antibody that blocks KIR/HLA-C interaction. We designed a study to evaluate the safety and efficacy of lirilumab as a single agent and in combination with azacitidine in patients with myelodysplastic syndrome (MDS). Patients and Methods: Adult patients with MDS who had not received previous hypomethylating agents were included. Lower-risk MDS patients received single-agent lirilumab (3 mg/kg); higher-risk patients received azacitidine (75 mg/m(2)/day for 7 days) in combination with lirilumab (3 mg/kg, on day 7), in a 28-day cycle. Responses were evaluated according to 2006 International Working Group criteria. Results: A total of 10 patients including 8 with higher and 2 with lower-risk enrolled. The median age was 70 (range, 50-84) years and 4 (40%) had complex cytogenetics. Baseline molecular mutations included TP53 (n = 5), TET2 (n = 3), and NRAS (n = 2). Patients received a median of 4 (range, 2-13) and 9 (range, 5-14) cycles of treatment with azacitidine with lirilumab and single-agent lirilumab, respectively. Two patients achieved complete remission (CR), 5 marrow CR, and 3 had stable disease. The median event-free survival for the entire cohort was 8 months (95% confidence interval, 4 months to not reached), and the median overall survival has not yet been reached. Five patients experienced 8 episodes of Grade >= 3 adverse events attributable to study drug, with the most frequent being infection or neutropenic fever (75%). Conclusion: Lirilumab either as a single agent as well as used in combination with azacitidine has clinical activity in patients with MDS. Further studies are needed to confirm our findings. (C) 2018 Elsevier Inc. All rights reserved.