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

Abstract

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.

• Authors: Fevzi Firat Yalniz, Naval Daver, Katayoun Rezvani, Steven Kornblau, Maro Ohanian, Gautam Borthakur, Courtney D DiNardo, Marina Konopleva, Jan Burger, Yvonne Gasior, Sherry Pierce, Hagop Kantarjian, Guillermo Garcia-Manero
• Journal: Clinical lymphoma, myeloma & leukemia (Clin Lymphoma Myeloma Leuk) Vol. 18 Issue 10 Pg. 658-663.e2 (10 2018) ISSN: 2152-2669 [Electronic] United States
• PMID: 30001986 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Antimetabolites, Antineoplastic
• Receptors, KIR
• Azacitidine

Topics

• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (therapeutic use)
• Antimetabolites, Antineoplastic (therapeutic use)
• Azacitidine (therapeutic use)
• Drug Therapy, Combination
• Female
• Follow-Up Studies
• Humans
• Male
• Middle Aged
• Myelodysplastic Syndromes (drug therapy, pathology)
• Pilot Projects
• Prognosis
• Receptors, KIR (antagonists & inhibitors)
• Survival Rate