Reconstitution of the multiple myeloma microenvironment following lymphodepletion with BCMA CAR-T therapy

BCMA-targeted CAR-T therapy has shown potent treatment outcomes in treating multiple myeloma (MM), a disease characterized by malignant bone marrow (BM) plasma cells. However, the remodeling of MM microenvironment after CAR-T therapy remains poorly understood. Here, we report the reconstitution of MM microenvironment by obtaining single-cell transcriptomes for paired BM specimens (n = 14) from 7 MM patients before (i.e., baseline, ''day −4'') and after (i.e., ''day 28'') post-lymphodepleted BCMA CAR-T therapy. Our analysis revealed heterogeneity in driver gene expression among MM cells, even those harboring the same cytogenetic abnormalities. The best overall responses of patients over the 15-month follow-up are positively correlated with the abundance and targeted cytotoxic activity of CD8+ effector CAR-T cells on day 28 after CAR-T cell infusion. Additionally, favorable responses are associated with attenuated immunosuppression mediated by regulatory T cells (Tregs), enhanced CD8+ eff..., The collected paired BM specimens from MM patients before and after BCMA CAR-T therapy were isolated into single cell suspensions, and 3'-scRNA-seq (Chromium Single Cell 3′ v3 Libraries) analysis was performed on each sample.
The analysis included 7 MM patients (P1-P7). We collected baseline BM aspirate specimens (P1_B, P2_B, P3_B, P4_B, P5_B, P6_B, and P7_B) from each patient before (i.e., baseline, ''day −4'') BCMA CAR-T cell infusion (i.e., ''day 0''), and the BM aspirate specimens (P1_R, P2_R, P3_R, P4_R, P5_R, P6_R, and P7_R) after BCMA CAR-T therapy were collected on day 28. These patients had received 2 or 3 previous lines of therapies, including two patients (P2 and P6) with extramedullary disease; the other patients did not experience extramedullary progression. All patients received cyclophosphamide-mediated lymphodepletion on day −3 with the aim of potentiating the expansion of CAR-T cells. Efficacy assessments based on the International Myeloma Working Group (IMWG) criteria ..., , # Reconstitution of the Multiple Myeloma Microenvironment Following Lymphodepletion with BCMA CAR-T Therapy

[https://doi.org/10.5061/dryad.44j0zpcn7](https://doi.org/10.5061/dryad.44j0zpcn7)

The collected paired BM specimens from MM patients before and after BCMA CAR-T therapy were isolated into single cell suspensions, and 3'-scRNA-seq (Chromium Single Cell 3' v3 Libraries) analysis was performed on each sample.

## Description of the data and file structure

The dataset includes '.mtx' files, each of which is for creating a Seurat object in R.

The naming convention of the '.mtx' files was following the sampling time points of the MM patients receiving BCMA CAR-T therapy. Specifically, the 14 BM specimens that performed scRNA-seq were collected from 7 relapsed or refractory MM patients (i.e. 'P1, P2, P3, P4, P5, P6, and P7') before and after BCMA CAR-T therapy. For these specimens, the baseline (i.e. 'B') specimens (P1_B, P2_B, P3_B, P4_B, P5_B, P6_B, and P7_B) were collected from ...