Table 4.
Biomarker studies for PD-1 blockade and pidilizumab therapy in B-cell lymphoma
| Reference | Drug and lymphoma type | Phase | ORR (%) | CR (%) | Biomarker/immune monitoring |
|---|---|---|---|---|---|
| PD-1 blockade in HL | |||||
| 20 | Nivolumab in R/R cHL | 1 | 87 | 17 | All 10 tumors examined had PDL1/PDL2 copy number alterations and PD-L1, PD-L2, and STAT3 expression; TILs largely expressed low levels of PD-1. |
| 21 | Pembrolizumab in R/R cHL that progressed after brentuximab vedotin | 1b | 65 | 16 | High prevalence (94%) of PD-L1 positivity in lymphoma samples; treatment increased T- and NK-cell numbers in the peripheral blood associated with IFN-γ, TCR, and expanded immune signaling gene signatures; however, all these changes were not predictive for treatment response. |
| 22 | Nivolumab in R/R cHL that failed to respond to auto-HSCT and brentuximab vedotin | 2 | 66.3 | 9 | PD-L1 expression on malignant Reed-Sternberg cells, but not PD-L1 expression on infiltrating normal cells, was associated with response. |
| 23 | Pembrolizumab in R/R cHL that progressed after auto-HSCT and/or brentuximab vedotin | 2 | 69 | 22.4 | High prevalence of PD-L1 positivity in lymphoma samples evaluated by staining intensity, membrane staining, and histiocyte score; 1 PD-L1− patient had progression; clinical activity was also seen in patients with low PD-L1 expression. |
| PD-1 blockade in B-NHL | |||||
| 107 | Nivolumab in R/R NHL and MM | 1b | FL, 40; DLBCL, 36; other NHL, 0; MM, 4 | FL, 10; DLBCL, 18; other NHL, 0; MM, 4 | PDL1/PDL2 genetic alterations were rare and seemed not to correlate with ORR. |
| 76 | Pembrolizumab in R/R CLL with RT and relapsed CLL | 2 | 44 for CLL with RT; 0 for relapsed CLL | 11 for CLL with RT; 0 for relapsed CLL | Increased PD-L1 expression in the pretreatment tumor specimens (mostly from the tumor microenvironment) was associated with response; increased PD-1 expression had a trend of association with response but it was not statistically significant; MSI status, EBV+, and baseline T cells in tumor specimens or peripheral blood were not associated with responses; none of the tested patients had 9p24 copy number gain or amplification. |
| Pidilizumab studies | |||||
| 104 | Advanced NHL, HL, CLL, and MM | 1 | 55.5 | 11 | During treatment, no changes in CD69+ lymphocytes and levels of IFN-γ or tumor necrosis factor-α were observed; a significant decrease in CD8+ lymphocytes was noted in patients who received 3 mg/kg. |
| 105 | CR/PR DLBCL after auto-HSCT (including 4 patients with PMBCL) | 2 | 51 | Treatment resulted in increases in absolute numbers of circulating memory T cells and PD-L1-bearing helper T cells and monocytes. | |
| 106 | Relapsed FL | 2 | 66 | 52 | Baseline PD-L1 (but not PD-1 or PD-L2) expression in peripheral blood CD4+, CD8+, and CD14+ cells correlated with ORR but not PFS; gene signatures at baseline indicating T-cell activation and effector T-cell (but not Treg) function in pretreatment tumor biopsies, as well as baseline signatures indicating function of effector T cells (PD-1intCXCR5int or PD-1lowCXCR5low) rather than TFH cells (PD-1highCXCR5high), predicted increased PFS; increased T-cell activation gene expression signatures after treatment with pidilizumab correlated with prolonged PFS. |
CR, complete remission; int, intermediate; MM, multiple myeloma; TCR, T-cell receptor.