CXCL13 levels are elevated in patients with Waldenström macroglobulinemia, and are predictive of major response to ibrutinib

Ibrutinib withdrawal symptoms in patients with Waldenström macroglobulinemia

“…However, recent data demonstrate ibrutinib induces significant suppression of inflammatory cytokines (i.e. TNFα, IL2RA and CXCL13), as well as a downregulatory effect on T-cells and macrophages [9][10][11][12]. It is possible that re-activation of both tumoral and microenvironmental cells during an ibrutinib hold could generate a cytokine release syndrome and cause the withdrawal symptoms reported here.…”

The BTK inhibitor ibrutinib may protect against pulmonary injury in COVID-19–infected patients

“…16 Serially collected blood samples from patients with chronic lymphocytic leukemia (CLL), WM, and cGVHD on ibrutinib monotherapy showed marked reductions in proinflammatory and chemoattractant cytokines that greatly overlapped with those reported to be elevated in the plasma of SARS-CoV-1 and SARS-CoV-2 patients, as well as in ACE2 1 cells from lung tissue of SARS-CoV-1 patients ( Table 2). 10,11,13,[21][22][23] In the ILLUMINATE randomized study, CLL subjects treated with ibrutinib immediately prior to infusion with obinutuzumab also showed significantly decreased levels of inflammatory cytokines associated with infusion-related reactions (a cytokine release syndrome). 24 These findings are consistent with a shift from an M1to an M2-polarized macrophage response following ibrutinib and are supported by preclinical and clinical studies showing dependence of macrophage lineage commitment on BTK function.…”

“…Table 2. Summary of proinflammatory and chemoattractant cytokine patterns in patients infected with SARS-CoV-1 and SARS-CoV-2 and following ibrutinib treatment in patients with CLL, WM, or and cGVHD He et al 10 Jiang et al 11 Huang et al 13 Niemann et al 21 Greil et al 24 Vos et al 22 Miklos et al 23…”

Spebrutinib (CC-292) Affects Markers of B Cell Activation, Chemotaxis, and Osteoclasts in Patients with Rheumatoid Arthritis: Results from a Mechanistic Study

“…Ibrutinib has been shown to directly inhibit CXCL13 production by macrophages in vitro [14]. Ibrutinib was shown to reduce blood CXCL13 protein levels in patients with mantle cell lymphoma [11] and Waldenstrom macroglobulinemia; high CXCL13 levels at baseline were associated with major clinical response in patients with Waldenstrom macroglobulinemia [15]. CXCL13 is highly relevant in the pathogenesis of RA, as high CXCL13 expression levels in the RA synovium have been associated with a lymphoid synovial phenotype; CXCL13 is more frequently observed in patients with RA who express anti-citrullinated protein antibodies and is a marker of more severe disease [16].…”