Killer immunoglobulin‐like receptor genotypes and chronic myeloid leukemia outcomes after imatinib cessation for treatment‐free remission

• Published in: Cancer medicine (Malden, MA) Vol. 8; no. 11; pp. 4976 - 4985
• Main Authors: Dumas, Pierre‐Yves, Bérard, Emilie, Bréal, Claire, Dulucq, Stéphanie, Réa, Delphine, Nicolini, Franck, Forcade, Edouard, Dufossée, Melody, Pasquet, Jean‐Max, Turcq, Béatrice, Bidet, Audrey, Milpied, Noel, Déchanet‐Merville, Julie, Lafarge, Xavier, Etienne, Gabriel, Mahon, François‐Xavier
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.09.2019; Wiley; John Wiley and Sons Inc
• Subjects: Aged; Antineoplastic Agents - therapeutic use; Biochemistry, Molecular Biology; Biomarkers; Cancer; Cell activation; Chronic myeloid leukemia; Clinical Cancer Research; Clinical trials; Cytotoxicity; Disease control; Female; Genes; Genetic Variation; Genotype; Genotype & phenotype; Genotypes; Haplotypes; Hematology; Human health and pathology; Humans; Imatinib; Imatinib Mesylate - therapeutic use; Immune system; Immunoglobulins; Immunology; Immunophenotyping; Inhibitor drugs; Killer cell immunoglobulin-like receptors; Killer Cells, Natural - drug effects; Killer Cells, Natural - metabolism; killer immunoglobulin‐like receptors; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - diagnosis; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Life Sciences; Ligands; Lymphoid cells; Male; Medical prognosis; Middle Aged; Myeloid leukemia; natural killer; Natural killer cells; Original Research; Patients; Potassium channels (inwardly-rectifying); Protein Kinase Inhibitors - therapeutic use; Protein-tyrosine kinase; Receptors, KIR - genetics; Receptors, KIR - metabolism; Receptors, KIR2DL5 - genetics; Remission; Remission Induction; Risk factors; Scholarships & fellowships; Solid tumors; Stem cells; Targeted cancer therapy; Transplants & implants; Treatment Outcome; treatment‐free remission; Withholding Treatment; killer immunoglobulin-like receptors; chronic myeloid leukemia; imatinib; natural killer; treatment-free remission
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.2371

Background Natural Killer (NK) cells are innate lymphoid cells that can be cytotoxic toward a large panel of solid tumors and hematological malignancies including chronic myeloid leukemia (CML). Such a cytotoxicity depends on various receptors. Killer immunoglobulin‐like receptors (KIR) belong to these receptors and are involved in maturation process, then in the activation abilities of NK cells. Methods: We investigated the prognostic impact of the KIR2DL5B genotype in 240 CML patients included in two clinical trials investigating tyrosine kinase inhibitors (TKI) discontinuation: STIM and STIM2. Results: After adjustment for standard risk factors in CML, we found that the inhibitory receptor KIR2DL5B‐positive genotype was independently related to a delayed second deep molecular remission (HR 0.54, 95% CI [0.32‐0.91], P = 0.02) after TKI rechallenge but not to time to first deep molecular remission or treatment‐free remission rates. Conclusion: These results suggest that KIR2DL5B could carry a role in lymphocyte‐mediated control of leukemic residual disease control in patient with CML relapse. We evaluated KIR genotype as immune biomarker of outcomes in patients from two prospective clinical trials addressing TKI cessation question and finally identified the role of KIR2DL5B in response to treatment at relapse after TKI cessation.