Identification of the Distinct Immune Microenvironment Features Associated with Progression Following High-Dose Melphalan and Autologous Stem Cell Transplant in Multiple Myeloma.

A key treatment for patients with multiple myeloma is high-dose melphalan followed by autologous stem cell transplant (ASCT). It can provide a deep response with long-term remission. However, some patients progress quickly, and it is not clear why. In this study, we performed single-cell RNA and T-cell receptor sequencing of the immune microenvironment of 40 patients before and after ASCT to determine if differences in the immune composition could define those who would progress. Clear differences in cell populations were identified in progressors, including increased T-cell infiltration, decreased T-cell receptor diversity, and decreased frequency of monocytes and CD56bright NK cells. We identified cell interactions that predicted progression, including increased frequency of CD8+ exhausted T cells and stromal cells and decreased frequency of CD56bright NK cells and plasmacytoid dendritic cells. We propose and validate a model of progression that can also be determined by flow cytometry. Together, these data highlight the importance of the immune microenvironment in understanding responses to ASCT.