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Yan Cheng, Ph.D., Fumou Sun, Ph.D., Bhavesh Mohan Lal, M.D., Toshali Pandey, MBBS
Publications
| Multi-omics reveal immune microenvironment alterations in multiple myeloma and its precursor stages
Blood Cancer Journal
November 2024
Primary authors: Yan Cheng, Ph.D.; Fumou Sun, Ph.D.
Tumor immune microenvironmental alterations occur early in multiple myeloma development. In this study, we aim to systematically characterize the tumor immune microenvironment (TME) and the tumor-immune interactions from precursor stages, i.e., monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma, to newly diagnosed multiple myeloma, comparing these to healthy donors. Using CIBERSORT, mass cytometry (CyTOF), and single-cell RNA sequencing (scRNA-Seq), we examined innate and adaptive immune changes across these stages. We found a decrease in granulocytes in the TME predicts multiple myeloma outcomes. HLA-DR is reduced in CD16+ monocytes and plasmacytoid dendritic cells, while myeloid dendritic cells show decreased expression of stress and immune-response genes. NK cells and CD8+ T cells shift from a GZMK+ to a GZMB+ cytotoxic phenotype in the TME, with increased inhibitory markers TIM3 and TIGIT. In paired samples, the proportion and gene expression pattern in patient-specific GZMB+CD8+ T cells remain largely unchanged despite multiple myeloma progression. Our findings provide a comprehensive immune landscape of multiple myeloma and its precursors, offering insights into therapeutic strategies. Enhancing neutrophil and NK cell cytotoxicity, tumor antigen presentation, and CD8+ T cell versatility in precursor stages may prevent multiple myeloma progression.
Chimeric antigen receptor T-cell therapy for relapsed/refractory multiple myeloma: a real-world experience
Bone Marrow Transplantation
April 2025
Primary authors: Bhavesh Mohan Lal, M.D.; Toshali Pandey, MBBS
B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy has significantly advanced the treatment of relapsed/refractory multiple myeloma. In the phase II KarMMa trial, idecabtagene vicleucel (ide-cel) achieved a median progression-free survival (PFS) of 8.8 months and overall survival (OS) of 19.4 months in triple-class-exposed relapsed/refractory multiple myeloma patients. Similarly, the phase Ib/II CARTITUDE-1 trial reported PFS and OS exceeding 27 months for ciltacabtagene autoleucel (cilta-cel). Between May 2021 and November 2023, 152 patients with relapsed/refractory multiple myeloma were listed to receive BCMA CAR T-cell therapy at UAMS. Out of the 152 patients, 72 patients completed apheresis, and 70 patients received BCMA CAR T-cell therapy at data cutoff. The median age of patients was 58 at diagnosis and 66 years at listing. The median number of years between diagnosis and listing was six years. No differences were found between patients who received CAR-T and those who didn’t in terms of gender, marrow burden, extramedullary disease, or age at listing.