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On 10th August, Josephine M. Vos from St. Antonius Hospital, Nieuwegein, The Netherlands, et al. published in Haematologica their investigation into the serum cytokine profiles of Waldenström Macroglobulinemia (WM) patients based on MYDD88 and CXCR4 mutation status, and how serum cytokine levels change in response to therapy with ibrutinib.
Firstly, samples from 86 patients off-therapy (first-line = 52; Relapsed/Refractory [R/R] = 34; MYD88L265P/CXCR4WT = 45; MYD88L265P/CXCR4MUT = 32; MYD88WT/CXCR4WT = 9) were compared to samples from age and gender matched Healthy Donors (HD; n = 20). Following this, samples were analyzed from 29 R/R WM patients who had received ibrutinib on a prospective clinical trial and had baseline and post-treatment serum samples taken one year after therapy initiation (MYD88L265P/CXCR4WT = 19; MYD88L265P/CXCR4MUT = 9; MYD88WT/CXCR4WT = 1).
Overall, 24 cytokines were analyzed and included the known WM biomarker CD27.
The authors state that their findings are the first to be published regarding changes in cytokine levels after ibrutinib therapy for WM. The group drew attention to the fact that their results mirror what has been previously found for Chronic Lymphocytic Leukemia (CLL) treated with ibrutinib, primarily changes in CXCL13, IL8, CXCL10, CCL4, CCL11, IL1RA, and TNFα. They hypothesize that these changes could be due to on-target tumor effects resulting in reduced cytokine production by lymphoplasmacytic lymphoma cells or the impact of ibrutinib on cells of the microenvironment e.g. T-cells, macrophages, etc.
It was also found that a high CXCL13 level at baseline strongly predicted the achievement of PR or better following one year of ibrutinib therapy, and deep suppression of CXCL13 was associated with major responses. To their knowledge, the authors state that there are currently no published findings of CXCL13 as a predictor of response to ibrutinib in CLL or other B-cell malignancies.
In conclusion, this group’s findings indicate a that CXCL13 has a key role in the tumor biology of WM, as well as in sensitivity to treatment with ibrutinib therapy. It is recommended that the accuracy and plausibility of CXCL13 as a biomarker for ibrutinib therapy, as well as a potential therapeutic target, is investigated in the future.
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