Increased Inflammatory Cytokines in Plasma Are Associated with Sustained Treatment-Free Remission in Chronic Myeloid Leukaemia

• Published in: Blood 2024-11, Vol.144, p.993-993
• Main Authors: Kok, Chung Hoow, Saunders, Verity A, Shanmuganathan, Naranie, Liu, Liu, Irani, Yazad Daruis, Clarson, Jade, Dang, Phuong, Yeung, David T, Yong, Agnes S. M., Branford, Susan, Pinilla-Ibarz, Javier, Larson, Richard A., Cortes, Jorge E., Mauro, Michael J., Thompson, James E, Shah, Neil P., Wadleigh, Martha, Atallah, Ehab L., Radich, Jerald P., Hughes, Timothy P, Ross, David M
• Format: Article
• Language: English
• ISSN: 0006-4971
• DOI: 10.1182/blood-2024-201881

Background: The immune status at the time of tyrosine kinase inhibitor (TKI) cessation may play a critical role in achieving sustained treatment-free remission (TFR) in chronic myeloid leukaemia (CML). Cytokine profiles may provide a measure of host immune activation against residual leukaemia. Aim: To investigate the expression of plasma cytokines at the time of TKI cessation (TOC) and assess their predictive significance for sustained TFR in two TFR cohorts from Australia (AU) and US. Methods: Blood was collected from 113 CML patients (pts) at TOC from an AU discovery cohort, 72 pts in the LAST study (US) as an independent validation cohort, and 20 healthy donors. The levels of 38 cytokines, chemokines and growth factors were measured in plasma samples using a MILLIPLEX Human Cytokine & Chemokine 38-plex panel and a Luminex 200 instrument. All samples were measured in duplicate and averaged. Unsupervised analysis was performed using t-Distributed Stochastic Neighbour Embedding. Multivariable model was performed with Cox proportional hazards regression. Hazard ratios (HR) and 95% confidence interval (CI) were reported for covariates, along with P values from the Wald test. All statistical analyses were conducted using the R v.4.1.1 and Prism GraphPad v9. Results: In the AU cohort most pts were treated with imatinib (51%), followed by nilotinib (31%) and dasatinib (17%) prior to TOC. The median duration of TKI and MR4 was 6 years (range 4.3-10) and 4 years (range 3.2-6.5), respectively. Median follow-up after TKI cessation was 24.2 months (mths; range 20.7-26.8). The probability of sustained MMR after TKI cessation at 12 and 36 mths was 54% (95% CI 46-64%) and 47.6% (95% CI 36-62%), respectively. We used an unsupervised analysis to group samples based on the similarity of their 38 cytokine expression profiles. Two distinct clusters in the AU samples were identified. Cluster 1 (n=62) had lower global 38-cytokines expression compared to cluster 2 (n=51, median 84 vs 104 pg/mL, p