Influence of Initial Multiple Myeloma Treatment on Immune Cell Repertoires, Recovery and Diversity

Drug therapy causes immune cell depletion in multiple myeloma patients at an age when cell regenerative capacity is usually decreased. Successful regeneration of vital immune cells requires the recovery of both quantity and quality of immune cell subclasses. Although immune cell numbers eventually rebound after a treatment, it is unclear whether overall compositional diversity is recovered. This might limit treatment options at later treatment lines, or complicate treatment with future immune therapies, and lead to suboptimal treatment outcomes. In addition, the influence of different first line treatment combinations on immune cell diversity in multiple myeloma has not been systematically evaluated.

We investigated the regeneration of immune cell complexity using mass cytometry and T cell receptor sequencing by comparing peripheral blood mononuclear cells from multiple myeloma patients coming off different first line treatment combinations at 6, 12 and 18 months after start of maintenance therapy.

Our study showed changes in patients' CD4+ and CD8+T cells regardless of the type of the initial treatment regimen. Recovery of CD4+ naive T cells was incomplete even after 18 months, but the highest rate of recovery was achieved when anti-CD38-containing combinations were used as the initial treatment. The degree of recovery was generally higher among CD8+ T cells regardless of the type of first line therapy. Natural killer cells (NK cells), dendritic cells and monocytes remained largely unaffected with all treatment combinations, with differences seen mainly at the rate of recovery. Similarly as for T cells, the amount of B cells also decreased, but their diversity remained notably altered even at 18 months, showing strong dependence on the type of therapy. The highest rate of recovery and diversity for B cells was achieved with anti-CD38-containing treatment regimens. The type of maintenance treatment also influenced the extent and rate of recovery.

Our data suggests that CD4 and B cells are more prone to permanent changes with specific treatment combinations, whereas other cell types recover to a larger extent. This data may be used to better understand the long-term consequences of initial treatment regimen selection, and provide support how to influence and maintain immune cell composition and diversity. The data may inform sequencing different therapies with the purpose of extending progression-free survival and enhanced disease control.

Saari:Chembrain LTD: Research Funding. Narashima:Chembrain LTD: Current Employment. Reinikainen:Chembrain LTD: Current Employment. Vuoti:Janssen-Cilag Europe: Ended employment in the past 24 months.