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Supplementary Figure from Changes in Bone Marrow Tumor and Immune Cells Correlate with Durability of Remissions Following BCMA CAR T Therapy in Myeloma

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posted on 2023-04-04, 01:42 authored by Kavita M. Dhodapkar, Adam D. Cohen, Akhilesh Kaushal, Alfred L. Garfall, Renee Julia Manalo, Allison R. Carr, Samuel S. McCachren, Edward A. Stadtmauer, Simon F. Lacey, J. Joseph Melenhorst, Carl H. June, Michael C. Milone, Madhav V. Dhodapkar
Supplementary Figure from Changes in Bone Marrow Tumor and Immune Cells Correlate with Durability of Remissions Following BCMA CAR T Therapy in Myeloma

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National Cancer Institute (NCI)

United States Department of Health and Human Services

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Leukemia and Lymphoma Society (LLS)

National Institute of Allergy and Infectious Diseases (NIAID)

United States Department of Health and Human Services

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ARTICLE ABSTRACT

Chimeric antigen-receptor (CAR) T cells lead to high response rates in myeloma, but most patients experience recurrent disease. We combined several high-dimensional approaches to study tumor/immune cells in the tumor microenvironment (TME) of myeloma patients pre– and post–B-cell maturation antigen (BCMA)-specific CAR T therapy. Lower diversity of pretherapy T-cell receptor (TCR) repertoire, presence of hyperexpanded clones with exhaustion phenotype, and BAFF+PD-L1+ myeloid cells in the marrow correlated with shorter progression-free survival (PFS) following CAR T therapy. In contrast, longer PFS was associated with an increased proportion of CLEC9A+ dendritic cells (DC), CD27+TCF1+ T cells with diverse T-cell receptors, and emergence of T cells expressing marrow-residence genes. Residual tumor cells at initial response express stemlike genes, and tumor recurrence was associated with the emergence of new dominant clones. These data illustrate a dynamic interplay between endogenous T, CAR T, myeloid/DC, and tumor compartments that affects the durability of response following CAR T therapy in myeloma. There is an unmet need to identify determinants of durable responses following BCMA CAR T therapy of myeloma. High-dimensional analysis of the TME was performed to identify features of immune and tumor cells that correlate with survival and suggest several strategies to improve outcomes following CAR T therapy.See related commentary by Graham and Maus, p. 478.This article is highlighted in the In This Issue feature, p. 476

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    Blood Cancer Discovery

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    cancer

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