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- Title
Immune modulation in chronic myeloid leukaemia patients treated with nilotinib and interferon‐alpha.
- Authors
Irani, Yazad D.; Hughes, Amy; Kok, Chung H.; Clarson, Jade; Yeung, David T.; Ross, David M.; Branford, Susan; Hughes, Timothy P.; Yong, Agnes S. M.
- Abstract
Summary: The addition of interferon to tyrosine kinase inhibitors (TKIs), to improve deep molecular response (DMR) and potentially treatment‐free remission (TFR) rates in chronic‐phase chronic myeloid leukaemia (CP‐CML) patients is under active investigation. However, the immunobiology of this combination is poorly understood. We performed a comprehensive longitudinal assessment of immunological changes in CML patients treated with nilotinib and interferon‐alpha (IFN‐α) within the ALLG CML11 trial (n = 12) or nilotinib alone (n = 17). We demonstrate that nilotinib+IFN transiently reduced absolute counts of natural killer (NK) cells, compared with nilotinib alone. Furthermore, CD16+‐cytolytic and CD57+CD62L−‐mature NK cells were transiently reduced during IFN therapy, without affecting NK‐cell function. IFN transiently increased cytotoxic T‐lymphocyte (CTL) responses to leukaemia‐associated antigens (LAAs) proteinase‐3, BMI‐1 and PRAME; and had no effect on regulatory T cells, or myeloid‐derived suppressor cells. Patients on nilotinib+IFN who achieved MR4.5 by 12 months had a significantly higher proportion of NK cells expressing NKp46, NKp30 and NKG2D compared with patients not achieving this milestone. This difference was not observed in the nilotinib‐alone group. The addition of IFN to nilotinib drives an increase in NK‐activating receptors, CTLs responding to LAAs and results in transient immune modulation, which may influence earlier DMR, and its effect on long‐term outcomes warrants further investigation.
- Subjects
CHRONIC myeloid leukemia; IMMUNOREGULATION; MYELOID-derived suppressor cells; REGULATORY T cells; INTERFERON alpha
- Publication
British Journal of Haematology, 2023, Vol 202, Issue 6, p1127
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1111/bjh.18984