Tumor burden quantified by soluble B-cell maturation antigen and metabolic tumor volume determines myeloma CAR-T outcomes
Abstract
Abstract Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a breakthrough treatment for relapsed and refractory multiple myeloma (RRMM). However, these products are complex to deliver, and alternative options are now available. Identifying biomarkers that can predict therapeutic outcomes is crucial for optimizing patient selection. There is a paucity of data evaluating the utility of both serum soluble B-cell maturation antigen (sBCMA) levels and metabolic tumor volume (MTV) at baseline in patients with RRMM undergoing CAR-T therapy. We identified a cohort of 183 patients with available serum to measure sBCMA and/or pretreatment MTV, derived from positron emission tomography–computed tomography scans obtained per standard of care. Expectedly, high pretreatment levels of sBCMA correlated with other established markers of tumor burden (eg, bone marrow plasma cells and β2 microglobulin) and inflammation and were highly prognostic for CAR-T–related toxicities and inferior progression-free survival (PFS). High MTV values were also associated with shorter PFS and inferior overall survival. The poor correlation observed between these 2 measures prompted evaluation of those with discordant results, identifying that those with low sBCMA and high MTV frequently had low/absent BCMA expression on plasma cells and suboptimal response. Our findings highlight the potential utility of sBCMA and MTV to facilitate more personalized treatment strategies in the management of RRMM eligible for BCMA-directed CAR-T.
Article Details
Authors (28)
Ciara L. Freeman
7Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Jerald Noble
1H. Lee Moffitt Cancer Center and Research Institute, Tampa, United States
Meghan Menges
1H. Lee Moffitt Cancer Center, Hematology and Oncology, Tampa, United States
Ricardo Villanueva
3Morsani College of Medicine, University of South Florida, Tampa, FL
Justyn Y. Nakashima
4Department of Radiation Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL
Nicholas B. Figura
4Department of Radiation Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL
Rolf Petter Tonseth
5Molecular Imaging and Therapy Program, BC Cancer, Vancouver, BC, Canada
Dietrich Werner Idiaquez
4Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Lawrence Skelson
1Department of Blood and Marrow Transplantation and Cellular Immunotherapy, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL
Eric Smith
Julieta Abraham-Miranda
H. Lee Moffitt Cancer Center, Tampa, Florida, United States
Salvatore Corallo
Gabriel De Avila
H Lee Moffitt Cancer Center, Tampa, Florida, United States
Omar A. Castaneda Puglianini
1Department of Blood and Marrow Transplantation and Cellular Immunotherapy, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL
Hien Liu
1H. Lee Moffitt Cancer Center and Research Institute, Tampa, United States
Melissa Alsina
H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States
Taiga Nishihori
Moffitt Cancer Center, Tampa, Florida, United States
Kenneth H. Shain
Rachid Baz
1Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Brandon Blue
Naval Research Enterprise Internship Program Student Residing in the Electronics Sciences and Technology Division, United States Naval Research Laboratory
Ariel Grajales-Cruz
1H. Lee Moffitt Cancer Center and Research Institute, Tampa, United States
John M. Koomen
8Department of Molecular Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL
Reginald M. Atkins
2Department of Clinical Science, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL
Doris K. Hansen
1Department of Blood and Marrow Transplantation and Cellular Immunotherapy, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL
Ariosto S. Silva
Jongphil Kim
6Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Yoganand Balagurunathan
1Moffitt Cancer Center, Department of Blood and Marrow Transplant and Cellular Immunotherapy, Tampa, United States
Frederick L. Locke