Immunophenotypic correlates of sustained MRD negativity in patients with multiple myeloma

David G. Coffey (), Francesco Maura, Edgar Gonzalez-Kozlova, J. Javier Diaz-Mejia, Ping Luo, Yong Zhang, Yuexin Xu, Edus H. Warren, Travis Dawson, Brian Lee, Hui Xie, Eric Smith, Amanda Ciardiello, Hearn J. Cho, Adeeb Rahman, Seunghee Kim-Schulze, Benjamin Diamond, Alexander Lesokhin, Dickran Kazandjian, Trevor J. Pugh, Damian J. Green, Sacha Gnjatic and Ola Landgren ()
Additional contact information
David G. Coffey: University of Miami
Francesco Maura: University of Miami
Edgar Gonzalez-Kozlova: Icahn School of Medicine at Mount Sinai
J. Javier Diaz-Mejia: University Health Network
Ping Luo: University Health Network
Yong Zhang: U.S. Food and Drug Administration
Yuexin Xu: Fred Hutchinson Cancer Research Center
Edus H. Warren: Fred Hutchinson Cancer Research Center
Travis Dawson: Icahn School of Medicine at Mount Sinai
Brian Lee: Icahn School of Medicine at Mount Sinai
Hui Xie: Icahn School of Medicine at Mount Sinai
Eric Smith: Dana-Farber Cancer Institute
Amanda Ciardiello: Memorial Sloan Kettering Cancer Center
Hearn J. Cho: Icahn School of Medicine at Mount Sinai
Adeeb Rahman: Icahn School of Medicine at Mount Sinai
Seunghee Kim-Schulze: Icahn School of Medicine at Mount Sinai
Benjamin Diamond: University of Miami
Alexander Lesokhin: Memorial Sloan Kettering Cancer Center
Dickran Kazandjian: University of Miami
Trevor J. Pugh: University Health Network
Damian J. Green: Fred Hutchinson Cancer Research Center
Sacha Gnjatic: Icahn School of Medicine at Mount Sinai
Ola Landgren: University of Miami

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: Abstract The role of the immune microenvironment in maintaining disease remission in patients with multiple myeloma (MM) is not well understood. In this study, we comprehensively profile the immune system in patients with newly diagnosed MM receiving continuous lenalidomide maintenance therapy with the aim of discovering correlates of long-term treatment response. Leveraging single-cell RNA sequencing and T cell receptor β sequencing of the peripheral blood and CyTOF mass cytometry of the bone marrow, we longitudinally characterize the immune landscape in 23 patients before and one year after lenalidomide exposure. We compare patients achieving sustained minimal residual disease (MRD) negativity to patients who never achieved or were unable to maintain MRD negativity. We observe that the composition of the immune microenvironment in both the blood and the marrow varied substantially according to both MRD negative status and history of autologous stem cell transplant, supporting the hypothesis that the immune microenvironment influences the depth and duration of treatment response.

Date: 2023
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DOI: 10.1038/s41467-023-40966-8

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