P219 | LOW-DOSE TYROSINE KINASE INHIBITORS PRESERVE IMMUNOMODULATORY EFFECT IN CHRONIC MYELOID LEUKEMIA PATIENTS

Background: Tyrosine kinase inhibitors (TKIs) represent the standard of care for CML patients (pts) and exert a dual mode of action: direct oncokinase inhibition and restoration of effector-mediated immune surveillance, which is dysfunctional in CML patients at diagnosis. The more recent goal of therapy in CML treatment is to induce a durable deep molecular response (DMR) as a prelude to successful treatment-free remission. It has been attributed to immunological control of CML thanks to an immune system re-activation and restoration of effector-mediated [natural killer (NK) cell and T cell] immune surveillance. In fact, as we observed in a previous abstract presented in 2019 the proportion of NK cells increased at achievement of DMR. Methods: We investigated how low-dose TKIs preserve immunomodulatory effect in pts who experienced a reduction of dose. A total of 24 pts were included in the study, 11 m and 13 f, with a median age of 59 (34-76). pts were treated with of imatinib (10), dasatinib (6), nilotinib (5) and ponatinib (3) with a median follow up of 8 years (5-16). Basic NK-, B- and T-cell proportions were analyzed with the flow cytometry NAVIOS using the following antibodies: CD45, CD3, CD16, CD56, CD4, CD8, CD19. A total of 48 analysis were performed. Results: After dose reduction all pts maintained molecular response and we did not observe any significant difference in lymphocytes subpopulation. Although the number of pts is limited, stratifying them based on TKIs, groups were not homogeneous but, in contrast to literature data, pts in treatment with imatinib showed an increased number of NK cells (median: 13%, range 6-20) compared to 2nd and 3rd generation TKIs (median: 11.5%, range 1-32) both before and after dose reduction. Conclusions: Our results, though limited to a small number of cases suggest that also after TKIs dose reduction immunomodulatory effect did not change and probably it was not dose dependent. This is a further element of support for the possibility of safely reducing TKIs dose in pts who have achieved a durable DMR.