Effect of avelumab on classic and PD-L1+ classic immune cell subsets
| Pre vs 1 cycle | Pre vs 9 cycles | |||||||
|---|---|---|---|---|---|---|---|---|
| Subset | Increase | Minimal change | Decrease | P-value | Increase | Minimal change | Decrease | P-value |
| A. Classic subsets | ||||||||
| CD4 | 0 (0%) | 18 (95%) | 1 (5%) | 0.0230 (↑^, 0.2070) | 0 (0%) | 12 (75%) | 4 (25%) | 0.0063 (↓^, 0.0567) |
| CD8 | 1 (5%) | 16 (84%) | 2 (11%) | 0.1447 (=) | 3 (19%) | 11 (68%) | 2 (13%) | 0.9799 (=) |
| Tregs | 7 (37%) | 10 (53%) | 2 (10%) | 0.2253 (=) | 2 (12%) | 7 (44%) | 7 (44%) | 0.0934 (=) |
| NK | 5 (26%) | 10 (53%) | 4 (21%) | 0.8288 (=) | 0 (0%) | 9 (56%) | 7 (44%) | 0.0182 (↓^, 0.1456) |
| NK-T | 2 (11%) | 15 (78%) | 2 (11%) | 0.2413 (=) | 1 (6%) | 12 (75%) | 3 (19%) | 0.1046 (=) |
| B cells | 5 (26%) | 12 (63%) | 2 (11%) | 0.7381 (=) | 6 (38%) | 5 (31%) | 5 (31%) | 0.8209 (=) |
| cDC | 3 (16%) | 15 (79%) | 1 (5%) | 0.3955 (=) | 6 (37%) | 7 (44%) | 3 (19%) | 0.7436 (=) |
| pDC | 6 (32%) | 8 (42%) | 5 (26%) | 0.4900 (=) | 6 (38%) | 9 (56%) | 1 (6%) | 0.0833 (=) |
| MDSC | 8 (42%) | 8 (42%) | 3 (16%) | 0.1232 (=) | 8 (50%) | 7 (44%) | 1 (6%) | 0.0833 (=) |
| B. PD-L1+ classic subsets | ||||||||
| PD-L1+ CD4 | 5 (26%) | 9 (48%) | 5 (26%) | 0.9843 (=) | 3 (19%) | 9 (56%) | 4 (25%) | 0.9999 (=) |
| PD-L1+ CD8 | 4 (21%) | 9 (47%) | 6 (32%) | 0.1688 (=) | 4 (25%) | 9 (56%) | 3 (19%) | 0.9999 (=) |
| PD-L1+ Treg | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a |
| PD-L1+ NK | 5 (26%) | 6 (32%) | 8 (42%) | 0.4180 (=) | 7 (44%) | 7 (44%) | 2 (12%) | 0.1046 (=) |
| PD-L1+ NK-T | 5 (26%) | 8 (42%) | 6 (32%) | 0.4900 (=) | 6 (38%) | 6 (38%) | 4 (24%) | 0.1439 (=) |
| PD-L1+ B cells | 9 (47%) | 6 (32%) | 4 (21%) | 0.6507 (=) | 6 (37%) | 7 (44%) | 3 (19%) | 0.5282 (=) |
| PD-L1+cDC | 5 (26%) | 8 (42%) | 6 (32%) | 0.3736 (=) | 2 (13%) | 4 (25%) | 10 (62%) | 0.0386 (↓*, 0.0772) |
| PD-L1+ pDC | 3 (16%) | 2 (10%) | 14 (74%) | 0.0258 (↓*, 0.0774) | 10 (63%) | 1 (6%) | 5 (31%) | 0.0443 (↑, 0.1005) |
| PD-L1+ MDSC | 8 (42%) | 6 (32%) | 5 (26%) | 0.6507 (=) | 10 (63%) | 4 (25%) | 2 (12%) | 0.0131 (↑, 0.1703) |
Classic subsets (A) and PD-L1+ classic subsets (B) were examined pre-therapy and post-1 cycle (n = 19) and 9 cycles (n = 16) of avelumab. Results are displayed as the number of patients (percentage of total patients) with an increase of more than 25%, minimal change of less than 25%, and a decrease of more than 25% compared to pre-therapy. Unadjusted p-values (= indicates no change; arrows indicate direction of change compared to pre-therapy; and Holm adjusted p-value is listed for subsets with significant unadjusted p-value) were calculated using the Wilcoxon matched-pairs signed rank test. n/a = not applicable as frequency of subset <0.01% PBMC; ^ = majority of patients with minimal change; * = difference in medians pre- vs post-therapy < 0.01
cDC conventional dendritic cells, MDSC myeloid derived suppressor cell, NK natural killer, pDC plasmacytoid DC, PBMC peripheral blood mononuclear cell, Tregs regulatory T cells