Summary of clinical trials that investigated the effect of B-cell receptor inhibitors on Th17 cell and/or IL-17 levels in patients with CLL
| Location . | No. . | Inhibitor investigated . | Key findings . | Reference (y) . |
|---|---|---|---|---|
| USA | 80 | Ibrutinib | Significant drop in blood Th17 cell (CD4+ CXCR3− CCR6+) frequency after 24 wk of ibrutinib treatment Ibrutinib displays an in vitro capacity to reduce murine Th17 cell differentiation in a dose-dependent manner | 173 (2016) |
| USA | 19 | IbrutinibAcalabrutinib | PMA/ionomycin stimulation of PBMCs from ibrutinib-treated patients with CLL shows a significant increase in percentage of Th17 cells Acalabrutinib-treated patients do not show similar increase in Th17 cells | 167 (2017) |
| USA | 10 | Idelalisib/ofatumumab | Idelalisib-ofatumumab therapy results in a significant increase in IL-17F–secreting CD8+ T cells in group of patients with CLL with high toxicity, which is associated with a reduction in Treg percentage In vitro, idelalisib and duvelisib can significantly increase Th17 cells and reduce Treg differentiation from healthy naïve CD4+ T cells | 170 (2019) |
| Germany | 9 | Idelalisib | Culturing CLL-derived CAR T cells in presence of idelalisib significantly increases Th17 (CCR4+ CCR6+) cell percentage on d 14 | 175 (2019) |
| USA | 20 | Ibrutinib | Ibrutinib treatment causes a transient increase in Th17F (IL-17F+) cells at second mo of treatment, which reverts to pretreatment levels at third mo | 146 (2021) |
| Italy | 71 | Ibrutinib/rituximab | Significant decrease in Th17 cell percentage after 18 mo of ibrutinib treatment and reduction in absolute Th17 cell counts starting mo 8 and up to mo 18 | 168 (2021) |
| USA | 26 | Duvelisib/FCR | Drug-induced toxicity is associated with an increase in CD4+ Th17 cells and related cytokines (IL-17A and IL-21) together with an increase in activated CD8+ T cells | 169 (2022) |
| Location . | No. . | Inhibitor investigated . | Key findings . | Reference (y) . |
|---|---|---|---|---|
| USA | 80 | Ibrutinib | Significant drop in blood Th17 cell (CD4+ CXCR3− CCR6+) frequency after 24 wk of ibrutinib treatment Ibrutinib displays an in vitro capacity to reduce murine Th17 cell differentiation in a dose-dependent manner | 173 (2016) |
| USA | 19 | IbrutinibAcalabrutinib | PMA/ionomycin stimulation of PBMCs from ibrutinib-treated patients with CLL shows a significant increase in percentage of Th17 cells Acalabrutinib-treated patients do not show similar increase in Th17 cells | 167 (2017) |
| USA | 10 | Idelalisib/ofatumumab | Idelalisib-ofatumumab therapy results in a significant increase in IL-17F–secreting CD8+ T cells in group of patients with CLL with high toxicity, which is associated with a reduction in Treg percentage In vitro, idelalisib and duvelisib can significantly increase Th17 cells and reduce Treg differentiation from healthy naïve CD4+ T cells | 170 (2019) |
| Germany | 9 | Idelalisib | Culturing CLL-derived CAR T cells in presence of idelalisib significantly increases Th17 (CCR4+ CCR6+) cell percentage on d 14 | 175 (2019) |
| USA | 20 | Ibrutinib | Ibrutinib treatment causes a transient increase in Th17F (IL-17F+) cells at second mo of treatment, which reverts to pretreatment levels at third mo | 146 (2021) |
| Italy | 71 | Ibrutinib/rituximab | Significant decrease in Th17 cell percentage after 18 mo of ibrutinib treatment and reduction in absolute Th17 cell counts starting mo 8 and up to mo 18 | 168 (2021) |
| USA | 26 | Duvelisib/FCR | Drug-induced toxicity is associated with an increase in CD4+ Th17 cells and related cytokines (IL-17A and IL-21) together with an increase in activated CD8+ T cells | 169 (2022) |