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/m²/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.