Bone Marrow CD4+ and CD8+ Lymphocyte Infiltration Patterns Define Overall- and Progression Free Survival in Multiple Myeloma and May Predict IMiD Response: an Analysis from the Austrian Myeloma Registry

Introduction:

In Multiple Myeloma immune dysregulation with quantitative and qualitative changes in T-cell subpopulations is thought to result in a reduced anti-tumour immune response promoting disease progression.

Methods:

A retrospective cohort of 45 myeloma patients was analyzed for the extent of tumor infiltrating CD4+ and CD8+ lymphocytes by means of immunohistochemistry using sophisticated automated evaluation software.

Results:

Here, for the first time we analyzed trephine biopsies of myeloma patients and we report a significant association of different patterns of immune cell infiltrations with OS and PFS suggesting that these patients might particularly benefit from immune modulating therapeutic strategies:

CD4+ T-cells below a cutoff of 0.28% lymphocytes/total nucleated cells were associated with a significantly longer overall survival, while CD8+ T-cells above the cutoff of 6.51% predicted a longer progression free survival. Treatment with immunomodulatory drugs resulted in a significantly better overall- and progression free survival for patients with adverse local immunological features compared to those treated with proteasome inhibitors or non-novel agents.

We suggest that immune dysregulation in myeloma significantly influences overall- and progression free survival. We will now validate this immuno algorithm of lymphocyte infiltration patterns as a predictive biomarker of IMiD responsiveness in the framework of a large randomized phase III trial. If confirmed they might be used as a putative biomarker to guide rational therapy allocation in the future.