Post-ASCT Pembrolizumab Maintenance Associated With Elevated Circulating DCs for DLBCL

According to a recent study, post-autologous stem cell transplant (ASCT) prembrolizumab maintenance therapy has been found to be associated with a persistent elevation of circulating dendritic cells (DCs) in patients with classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL; Transplant Cell Ther. 2022 Jan; epub ahead of print).

“ASCT is a standard of care for patients with chemo-sensitive, relapsed/refractory (R/R) cHL and DLBCL,” explained Reid W Merryman, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, and co-authors. “Whereas the clinical benefit of ASCT has traditionally been attributed solely to cytoreduction from intensive chemotherapy, ASCT has important immunogenic effects that may contribute to its antitumor efficacy and could provide a favorable immune environment for post-ASCT immune-based maintenance treatments.”

Thus, Dr Merryman et al aimed to characterize the impact of pembrolizumab on immune reconstitution by comparing the kinetics of peripheral blood immune cell recovery after ASCT for patients with R/R cHL and DLBCL given pembrolizumab maintenance therapy versus a control cohort of similar patients undergoing ASCT without pembrolizumab maintenance, as well as identify efficacy biomarkers and immune-related adverse events (AEs). 

Researchers collected peripheral blood mononuclear cell samples from 1 to 18 months after ASCT and analyzed them by flow cytometry using a panel of fluorophore-conjugated monoclonal antibodies to identify B cells, natural killer cells, and various dendritic- and T-cell subsets. 

Overall, a median of 5 post-ASCT peripheral blood samples were collected from 144 patients (59 in the pembrolizumab group; 85 in the control cohort).

Researchers determined that the clinical characteristics of the 2 cohorts were alike. Compared with cHL patients, DLBCL patients had delayed CD19+ cell reconstruction that persisted for at least 18 months after ASCT. There were no other differences on immune reconstruction based on lymphoma subtype observed. 

Post-ASCT pembrolizumab maintenance therapy was associated with elevated circulating DCs that persisted for the duration of treatment, along with a significant reduction in PD-1+ T-cells that persisted for 6 to 12 months after the treatment was complete. Pembrolizumab maintenance did not affect recovery of any T-cell subsets.

In an exploratory analysis, a higher baseline CD4+ terminal effector memory cell count was associated with inferior PFS, but only in the pembrolizumab maintenance cohort (P = .003). As continuous variables, lower absolute levels of NK cells (P = .009), PD-1+ CD4+ T cells (P = .005), and PD-1+ CD8+ T cells (P = .005) before pembrolizumab was given were each associated with a higher risk of grade 2+ immune-related AEs.

“Our findings indicate that post-ACST pembrolizumab maintenance therapy is associated with a persistent elevation of circulating DCs, but its impact on the reconstitution of other immune cells in peripheral blood appears limited. Our study suggests that early features of post-ASCT immune reconstitution could be associated with PFS and the risk of immune-related AEs and warrant additional investigation,” concluded Dr Merryman et al.—Emily Bader