Immuno-oncology

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Low Natural Killer Cells Counts Are Associated with Relapse After Imatinib Discontinuation in Chronic Myeloid Leukemia Patients : The Immunostim Study

Friday, June 16
6:15 PM - 7:30 PM

Despite leukemic stem cell persistence, patients with chronic myeloid leukemia (CML) who achieve and maintain deep molecular responses can successfully stop treatment with the tyrosine kinase inhibitor (TKI) imatinib. However, questions remain unanswered regarding the clinicobiological basis of relapse after imatinib cessation. In the IMMUNOSTIM study, we evaluated 51 patients from the prospective STop IMatinib (STIM) trial for peripheral blood T- and natural killer (NK)-cells phenotypes and in vitro functional assays at the time of imatinib cessation and 6 months later. We found that non-relapsing patients displayed significantly higher numbers of circulating NK-cells of the cytotoxic CD56dim subset at imatinib discontinuation than relapsing patients. We identified the CD56dim NK-cell count as an independent prognostic factor of molecular-relapse free survival in a multivariate analysis. However, compared with healthy individuals, NK activating receptors, degranulation in response to leukemic targets and cytokine-induced IFN-γ secretion were impaired in non-relapsing and relapsing patients. After imatinib cessation, NK-cells significantly increased and remained higher in non-relapsing patients with higher levels of the mature CD57+ NK subset. In conclusion, we provide evidence that NK-cells are associated with outcome after imatinib discontinuation in chronic phase CML patients in deep molecular response. Higher amounts of cytotoxic CD56dim NK-cells in non-relapsing patients may play an important role in controlling residual CML-initiating cells and their progeny soon after cessation of imatinib treatment while a reduced CD56dim compartment in relapsing patients may leave less chance to counterattack in an efficient manner.

Nicolas Dulphy

INSERM U1160, Université Paris Diderot, APHP, Hôpital Saint-Louis

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    Delphine Rea

    INSERM U1160, Université Paris Diderot, APHP, Hôpital Saint-Louis

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      Guylaine Henry

      INSERM U1160, Université Paris Diderot, APHP, Hôpital Saint-Louis

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        Gabriel Etienne

        Service d'Oncologie Médicale, Institut Bergonié, Bordeaux, France.

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          François Guilhot

          INSERM CIC 1402, CHU de Poitiers, France.

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            Franck Nicolini

            Service d'Hématologie Clinique, CHU Lyon Sud, Pierre Bénite, France.

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              Joelle Guilhot

              INSERM CIC 1402, CHU de Poitiers, France.

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                Philippe Rousselot

                Service d’Hématologie Oncologie et INSERM UMR-1173, Centre Hospitalier de Versailles, Le Chesnay, France.

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                  Antoine Toubert

                  INSERM U1160, Université Paris Diderot, APHP, Hôpital Saint-Louis

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                    Low Natural Killer Cells Counts Are Associated with Relapse After Imatinib Discontinuation in Chronic Myeloid Leukemia Patients : The Immunostim Study



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