Immunophenotypic correlates of sustained MRD negativity in patients with multiple myeloma

• Published in: Nature communications Vol. 14; no. 1; pp. 5335 - 12
• Main Authors: Coffey, David G., Maura, Francesco, Gonzalez-Kozlova, Edgar, Diaz-Mejia, J. Javier, Luo, Ping, Zhang, Yong, Xu, Yuexin, Warren, Edus H., Dawson, Travis, Lee, Brian, Xie, Hui, Smith, Eric, Ciardiello, Amanda, Cho, Hearn J., Rahman, Adeeb, Kim-Schulze, Seunghee, Diamond, Benjamin, Lesokhin, Alexander, Kazandjian, Dickran, Pugh, Trevor J., Green, Damian J., Gnjatic, Sacha, Landgren, Ola
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02-09-2023; Nature Publishing Group; Nature Portfolio
• Subjects: 38/39; 631/250/1619/554/1834/1269; 631/250/2502; 631/67/1990/804; 631/67/327; Blood; Bone marrow; Bone mass; Cytometry; Gene sequencing; Humanities and Social Sciences; Humans; Immune response; Immune system; Immunophenotyping; Lenalidomide; Lymphocytes; Lymphocytes T; Microenvironments; Minimal residual disease; multidisciplinary; Multiple myeloma; Multiple Myeloma - drug therapy; Patients; Peripheral blood; Receptors, Antigen, T-Cell, alpha-beta; Remission; Science; Science (multidisciplinary); Stem cell transplantation; Stem cells; T cell receptors; Tumor Microenvironment
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-40966-8

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.
How the immune response is involved in the response to multiple myeloma after treatment is not fully understood. Here the authors investigate how lenalidomide treatment in newly diagnosed MM patients affects the immune microenvironment in the blood and bone marrow and compare between responses to treatment.